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in Diving Vertebrates1


John B. Pierce Foundation Laboratory, New Have, Cmmecticut I; In~oduction ......................................................... II. Historical Survey. .................................................... III. Respiration in Diving Vertebrates ...................................... A. Respiratory dimensions. ............................................ B. Pulmonary ventilation. ............................................ C. Blood ............................................................ D. Oxygenin muscles.. .............................................. E. Metabolism in diving animals ....................................... F. CO2 sensitivity of respiration. ....................................... G. Respiratory responses to lack of 02 .................................. H. Acid-base changes ................................................. IV. Cardiovascular Adjustments to Diving. .................................. A. Bradycardia ...................................................... B. Bloodpressure .................................................... C. Cardiac output ................................................... D. Distribution of circulating blood. .................................... V. Nervous Mechanisms ............................................... VI. Diving Responses in Man under Normal and Pathological A. Hu~div~ .................................................... B. Asphyxia at birth ................................................. C. Oxygen-conserving reflexes in disease ................................ VII. General Conclusions. .................................................

213 216 216 2x7 2x8 219

220 221 222


223 223 223 225 227 228 ; . 232 .... 236 236 238 238

Acute respiratory arrest in man and most other air-breathing vertebrates causes great discomfort, loss of consciousness, and convulsive efforts to breathe. If breathing remains obstructed, death is certain within a few minutes. It is obvious, therefore, why the diving performance of certain aquatic vertebrate animals has been intriguing to laymen in general and physiologists in particular. Roughly IOO years ago scientific ideas and methods had progressed far enough to allow an experimental inquiry into the phenomenon of prolonged diving in vertebrate animals. Today the physiological modifications that enable the divers to remain under water for long periods of time are largely understood. Interest is shifting accordingly from the functional adjustments themselves to the mechanisms by which they are elicited, controlled, and integrated. When such a change of emphasis occurs in a scientific field, it may be worth while to epitomize the work that has brought about the transition and to point out the new trends. Such is the purpose of this review.
1 Supported in part by Nansenfondet and Prof. R. Colletts legat. 3 On leave from the Institute of Zoophysiology, University of Oslo, Blindern, Present address: Institute for Nutrition Research, University of Oslo, Norway.


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Several accounts of the physiology of diving vertebrates have appeared recently (I I, 6 I, I I t&120), but the pertinent literature has not been surveyed since Irvings review in r g3g (sg), which was devoted largely to diving mammals. It thus seems appropriate to introduce our subject in a historical perspective rather than to scrutinize exclusively the literature of the last quarter of a century.

The first systematic studies of diving vertebrates were published by Paul Bert (I 7) in 1870. Although preceded in the literature by occasional references to the ability of divers to survive prolonged submersions (22, 42), Berts work was a pioneering endeavor. The fact that his explanation of the phenomenon has been proven inadequate does not dismiss him as the founder of the physiology of diving. Initially, Bert established what is usually taken for granted: that the natural divers are, indeed, able to endure underwater conditions more successfully than their terrestrial relatives. This point is documented in Table I. Bert attempted to explain this difference between divers and nondivers by comparing the hen and the duck. He pointed out that the duck, although it shows many morphological adaptations to life in an aquatic environment, has no accessory respiratory organs by which 02 is obtained from water. On the other hand, he observed that the
TABLE I. Duration of dives jwrfwmed by diving and nondiving birds and mammals Animal Pigeon* Hen* Duck, domestic (white Peking) Penguin, Pygoscelis fiaflua t Penguin, Eudyptes chrysolo~hus Guillemot, Uris grylle and U. troile* P&in, Mormon fratercula* White rat* Rabbit Cat* Dog* Muskrat, Ondatra zibethica* Beaver, Castor canadensis Grey seal, Halichoerus gryjws Bladdernose, Cystophora cristata Sperm whale, Physeter catodon Bottlenose, Hyfieroodon rostratus Blue whale, Balaenojtera musculus Fin whale, Balaenopteta plupalis Finback whale, Balenoptera physalus Florida manatee, Trichechus latirostris Man, experienced skin diver (exercise) Man, experienced skin diver (at rest) * Average time to last movement by forced submersion. t Latin terminology is according to the author quoted.
Time, min
I 20 20


3 15 7 5

3 ==7 ==7
20 20 =7


3 3 4

18 18 75

50 30 30 15 I

=7 =7 =7 59 59 117 ==7 59 59 59 59 59 123 96 ,

96 ,

I22 I22




ratio of blood volume/body weight is considerably larger in the duck than in the hen. Thus, the duck is able to store much more 02 than the hen. Bert felt this explained the ability of the duck to remain under water, and proved his hypothesis to his satisfaction by bleeding ducks until their ratios of blood volume to body weight had been reduced to that of hens. On repeated submersion of bled ducks he found them to succumb as rapidly as hens. Twenty-four years passed before Berts conclusion was challenged by another great -French physiologist, Charles Richet (108). He accepted Berts data on the large blood volume in the duck and its role as a potential store for 02, but argued that such a small extra amount of 02 would be insufficient to meet the requirements. during a long dive. Together with Langlois (84, 85) he analyzed the composition of gas in the lungs and air sacs of diving ducks and found that the consumption of OS decreased markedly during a dive. Richet also performed an experiment revealing that water immersion in itself is important for survival during respiration arrest in natural divers: he occluded the trachea in two groups of ducks and let the subjects in one group suffocate in air and the others in water. Those immersed in water lived, on the average, 23 min, whereas those left in air perished in approximately 7 min. What is remarkable, therefore, in this diving bird, and probably in all vertebrate divers, is the ability to survive prolonged submersion asphyxia, not just arrest of breathing. Richet concluded that the 02 deposits of ducks do not suffice for anaerobic metabolism at the prediving level, and he suggested that physiological adjustments take place so that the oonsumption of 02 decreases during diving. He also indicated that tissue combustion, on the whole, is reduced during submergence (I 12). At about the same time, Bohr (20) published a study on the physiology of aquatic birds. Unfortunately, his paper is written in Danish and is therefore not widely known. Bohr also realized that the amount of 02 deposited in the tissues of diving birds is too small to suffice during prolonged submersions. He suggested, however, that enough energy is derived from an increase in anaerobic processes to compensate fully for the diminished 02 consumption. The same idea was later entertained bv Dill and Edwards (Is), working with the crocodile Crocodylus acutus. The question of metabolic changes in divers has been investigated further during the period of time covered in this review; the main discussion of the subject is found on p. 220. Studies of the diving vertebrates seem to have been suspended for more than a decade after Richets final paper (I I I), until in I 913 six important papers by Huxley (52-54), Lombroso (8g), Noel Paton (g4), and Orr and Watson (98) appeared almost simultaneously. The first of the three papers by Huxley (52) deals with a question already debated by Beau (16) and Bert (I 7). Beau had suggested that the apnea observed during submersion is reflexly initiated by immersion into water, whereas Bert held the opinion that breath-holding during diving is voluntary. Huxley demonstrated that on submersion apnea takes place in decerebrated ducks as well as in intact ones, thus proving its independence of higher levels of the central nervous system. Her second paper (53) relates the discovery that the same physiological responses elicited when a diver is immersed into water may be produced also in the duck breathing air if the bird is made to assume its diving pos-

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ture. She referred to this as a postural reflex, and Noel Paton in the same laboratory showed it to depend in part on impulses traveling over cervical nerves and in part on labyrinthine functions (94). In her last paper Huxley (54) presented evidence that diving bradycardia develops in decerebrated ducks as well as in intact birds. Curiously, these latter experiments were carried out keeping the subject in a position that the author had already shown to produce postural apnea and cardiac slowing. Therefore, the cardiac effect could have been due to the posture rather than to the immersion into water. Koppanyi and Kleitman (81), exploring the postural reflexes further, expressed the opinion that postural apnea does not reinforce submersion apnea, since they were unable to demonstrate postural apnea when keeping the duck in its normal .diving position. Koppanyi and Dooley (79) later arrived at the conclusion that the wetting of the beak, nostrils, and mucous membranes of the nasal cavity is the cause of apnea during submergence, thus supporting a suggestion previously offered by Vincent and Cameron (132). In a subsequent paper in which Koppanyi and Dooley described the postural apnea in muskrats (Fiber ~ibethicus) this postural reflex was also admitted, however, to be of value during diving (80). Postural apnea has been also demonstrated in at least two other diving birds, the swan (Cygnus olor) and the cormorant (Phalacrocorax carbo) (95). Also in ig13, Lombroso (89) conducted an investigation of the causes of cardiac retardation during diving, trying for the first time to separate the effects of actual water immersion and asphyxia. On occlusion of the trachea of the duck, he did not observe a diving-like bradycardia. When ventilating the lungs and air sacs of submerged ducks with a pair of bellows, he reported that no consistent changes in the diving bradycardia were produced although he frequently did note cardio-acceleration. He suggested that afferent impulses mediated over the trigeminal nerve play a part in eliciting the diving bradycardia, in support of the view held by Beau (I 6) and Richet (I I I, I I 2). Last among the papers from I 913 is the one by Orr and Watson (98). They studied the respiratory effects of lactic acid, low 02, and high CO2 in the duck. This paper, the first investigation of its kind using diving vertebrates, is well known and frequently cited in the literature. Unfortunately, this fine study introduced the erroneous concept that CO2 does not stimulate respiration in divers. However, the responsibility for this fallacy is to be shared equally by these authors, who did not realize the limitations of their data, and by later workers who not only accepted the interpretations of OIT and Watson, but in addition extended the significance of their findings to mean that CO* inhibits respiration in diving birds. Since the problem has been reinvestigated several times in the duck as well as in other vertebrate divers and because the subject has been controversial, Orr and Watsons original paper is reviewed along with more recent contributions (p. 22 I). In the 1930% great progress was made toward an understanding of the mechanisms that enable diving vertebrates to remain under water for prolonged periods of time without harm. An epitome of the early writings of Irving (55-59) and Scholander (I I 7) will show this clearly, since these two men have probably contributed more to our knowledge of the physiology of diving animals than anyone else.



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Irving, in presenting his viewpoints in a pithy article (55), emphasized the necessity of a continuous supply of oxygen in man and other homeothermic animals: he rejected the idea that vertebrate divers carry enough oxygen to perform prolonged submergence, pointed out that the brain and possibly also the heart are easily and irreparably damaged by lack of oxygen, asserted that the muscles may be left hypoxic for relatively long periods of time without ill effects, and concluded, I feel that when we can find neither chemical nor physical processesin the avian or mammal body which would adapt them for submergence, that we should turn our attention to reflex adjustment. Later research has verified practically every point in his paper. In a series of papers published during the second half of the decade, Irving demonstrated that CO2 stimulates respiration to a lesser extent in beavers (Castor canadensis), muskrats (Ondatra zibethica), and seals (Phoca vitulina) than in strictly terrestrial animals (58). He showed that respiratory arrest causes an increase in cerebral blood flow whereas muscle blood flow diminishes (57), and attention was drawn to the very fine control of peripheral circulation in the seal (67). Irving observed, however, that the physiological adjustments to submergence are not unique among the diving vertebrates, but rather are developed to a remarkable degree compared with their terrestrial relatives (56). These various findings have been summed up and discussed in sufficient detail in Irvings review (59). Scholanders monograph on the physiological responses of diving mammals and birds (I I 7), published in I 940, is still today the most comprehensive and important single effort in the field of diving physiology. Scholander studied respiratory and metabolic parameters in particular. His ingenious methods permitted continuous recording of 02 consumption, CO2 excretion, ventilation and respiratory rate, before and after diving; the amount of 02, CO% and lactic acid in arterial blood were also determined in every experiment. Since the information provided by Scholander is so diverse, and since it has served as a basis for further explorations in many different directions, his work is not appraised briefly here, but its various aspects are reviewed in their appropriate context. By the time Irvings review (59) and Scholanders monograph (I I 7) appeared in print, these two investigators had united in their efforts. This marks the beginning of the period of scientific work that is the principal concern of this review.

A. ResfCratory Dimensions

Data on the respiratory dimensions in diving vertebrates are scarce. Only a few mammalian divers have been studied (62, I 23), as shown in Table 2, where the corresponding figures for man are given for comparison. Except for the large whales, lung volumes compared to body weight do not differ much among the animals listed. The relatively small lung volumes of the bottlenosed whale and the fin whale may appear strange, since both of these species are known to be good divers (Table I). However, these animals are known

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TABLE 2. ResfCratory dimensions diving animals compared to those

Animal Resting Ot ml/xoo kg/min

certain homeothermic man*

l/100 kg/min

990 55 375 585 240 280


LWI Volume, l/rco kg

Seal Manatee Porpoiset Porpoise $ Bottlenose Fin whale Man * Refs. 62, 123.


415 t Phocaena communis.

5-3 5*9 2.5 2.9 11.7

5-o 5J 6.9 6.6 2-5 2-9 5*o

I .8 2*9 5*4 569 2.2


8-10 8-10

2.5 0.8

8-10 4-5

$ Tursiops truncatus.

to descend to great depths (51, SS), and a small lung volume may prevent caisson diseasein the whales. This interpretation is supported by Scholander (I I T), who suggested that the lungs of the whales may collapse rapidly during descent because they are not firmly attached to the wall of the thoracic cavity. Since the volume of the respiratory dead space in the whales is approximately one-tenth the volume of the lungs, at a depth of IOO m all the air from the collapsing lungs may be contained in the dead space. The diffusion barrier thus created is believed to cause an appreciable slowing of the rate at which Nz dissolves in the blood of a deep-diving whale. In fact, equilibrium between gas tensions in lungs and arterial blood is not established at all in a deep dive if this assumption is correct. Consequently, these whales need dispose of only a relatively small amount of dissolved Nz during ascent. The disadvantage is that the diffusion of 02 from the lungs to the blood would be similarly impaired. However, none of the diving vertebrates seem to take full advantage of the lungs as a potential deposit of 02, for it is well known that seals prefer to exhale before descent (I I 7), and diving birds and reptiles are commonly observed to dive on expiration (5, 33, I 17). Again, in seals and other mammals that, like the whales, dive fairly deep, expiration just prior to diving may serve to prevent decompression sickness. Likewise it may be a preparatory adjustment of buoyancy (9). But even in aquatic animals that rarely dive deep, like the duck for example, exhaling of air is frequently seen on submergence. The reason for this has not been studied, but it has been observed that avian divers failing to blow off air in the beginning of a submersion tend to develop diving bradycardia and presumably other circulatory adjustments, only very slowly (6, 7, 33). If distention of lungs, and of the air sacs in birds, gives rise to afferent nervous impulses that influence the heart rate (Hering-Breuer reflex), exhaling of air prior to or on submersion may facilitate the onset of diving bradycardia and other circulatory changes seen during water immersion (6, 7). Because most diving vertebrates exhale a large quantity of the lung gases on descent, estimates of the amount of oxygen available to the divers during submersion are somewhat uncertain.
B. Pulmonary Ventilation

The tidal volume, when related to body weight, is from 2 to 8 times larger in diving mammals than in man. A large fraction of the total lung air is therefore



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renewed by each breath. Scholander and Irving (123) assumed that all whales, like the porpoises, nearly empty their lungs during expiration. This large exchange of gas per breath is associated with a slow respiratory frequency. When the tidal volume approaches the total lung volume, the pulmonary ventilation can be increased only by means of a faster frequency of breathing. However, the pulmonary ventilation in large mammalian divers was observed to fall during the early period of recovery after a dive if the respiratory rate increased much, because such an increased rate resulted in a marked drop in the tidal volume (62, 123). The ability to increase pulmonary ventilation by a simultaneous increase in tidal air and respiratory rate is markedly low in the seals and the manatee and almost absent in the. whales. The slow respiratory rate of the mammalian divers causes a high degree of utilization of the 02 in the inspired air even in the resting state (Table I), and the content of COs in their expired air is about twice that of man. Similar information of reptilian and avian divers is not available.

c. Blood
The. blood volume and its 02 capacity in some diving and nondiving reptiles, birds, and mammals are presented in Table 3. In most cases the divers store a larger amount of O2 in the blood than do the terrestrial animals. Reliable data on the content of 02 in the arterial and especially in the venous blood just on submersion are sc,arce. Analytical determinations of 02 in reptilia n and avian blood possessan add itional uncertain ty because these animals have nucleated red cells that consume 02 at a rapid rate. Also, estimates of the amount of O2 carried in the
TABLE 3. Blood volume and oxygen capacity of blood of

some diving and nondiving species


Blood Volume,% of body wt. PO 3*9


02 C$ a$ty, P 21.2 II .2

Ref. 2% I33 17, I36 133

20 20 117 101 101

Pigeon Hen Duck, domestic Guillemot, Uris troile Puffin, Mormon fratercula Penguin, Pygoscelis PaPua Man Dog Horse Rabbit Beaver, Castor canadensis Muskrat, Ondatra zibethica Seal, Phoca vitulina Sea lion, Eumetopias stelleri Porpoise, Phocaena communis Blue whale, Balenoptera musculus Fin whale, Balaenojteta plupalis Sperm whale, Physeter catodon * Blood samples drawn from carcasses up

12.3-13.7 II .3-12.0 9*0 6.2-7.0 6.2-10.5 7 .o-10.7 6.5


x6.9 26.0 24.0

20.0 20.0 21.8

16.7, 15.6


101 101

5*9 15.0 25.0 29-3 19.8 20.5 14.1 14.1

59 59 66 38 43 86 86 43


several hours after death.

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blood at the beginning of a dive are complicated by the fact that we do not know how large a fraction of the blood is arterialized at any particular time. An interesting difference in the properties of reptilian blood sampled from aquatic and terrestrial species, respectively, has been reported by Dill and coworkers (27-29, 32). They found that acidification has a pronounced effect in decreasing the affinity of hemoglobin for 02 in the crocodile (CrocodyZ~s a&us) and in the alligator (Alligator mississippiensis),whereas this effect (Bohr effect) was much less in the chuckwalla (Sauromalus obesus) and the gila monster (Heloderma suspecturn): Thus, unloading of 02 from the blood at a certain Paz and Pcoz is facilitated to a greater extent in the crocodilians than in the terrestrial species. Likewise, at any percentage of saturation considered, the Pd, in the blood of the divers will be higher than in the nondivers. These properties of the blood of the diving reptiles may be regarded as advantageous in ensuring full utilization of the oxygen available while keeping the PO, at a reasonably elevated level.
D. Oxygen in Muscles

Muscles of diving mammals are normally dark, due to their large content of myoglobin (I 30). It has been suggested that oxymyoglobin constitutes a very valuable store of 02 in permitting mammalian divers to remain submerged for prolonged periods of time. Robinson (I 14) determined the myoglobin content in seal muscles and calculated that the 02 deposited here might constitute up to 47 % of the total amount available during submersion. He concluded that the myoglobin is the most important depot of 02 for protracted diving in the seal. This argument is fallacious, however, for the following reason: first, although myoglobin combines very readily with 02, being 50 % saturated at a Paz of 3.26 mm Hg at pH 7.4 (I 3 I), hemoglobin is 50 % saturated only at a Pas of about 30 mm Hg at the same pH. Thus, the 02 deposited in the muscles is strictly confined to this tissue. Second, if the muscles are perfused with blood during diving, the hemoglobin of the blood loses 02 to the myoglobin, because of the IO-times-higher affinity for 02 of the latter. Consequently, it does not appear to be beneficial to channel blood through the muscles in normal fashion during diving. Instead, the ideal solution would be to check the muscular blood flow or to exclude the metabolizing part of this tissue from the circulation. There are many reports of marked changes in the muscular circulation in submerged divers (3, 49, 57, 74, I I 7, 124). The pertinent literature is reviewed on p. 228. The 02 capacity of various muscles in the seal (Halichoerus grypus) have been determined by Scholander (I I 7) (Table 4).
TABLE 4. 0 xygen capacity of seal muscles (Halidioerus gryfw)*
02 Capacity, vol %

M. rectus abdominis M. pectoralis Heart Diaphragma * From Scholander

3.8-5.0 493-5 l 5 3*7





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E. Metabolism in Diving Animals

Quantitative comparisons between the amount of 02 available from the main deposits and the resting 02 consumption have been made in a few divers only. Table 5 presents some data for this purpose; however, one should recall the various sources of error involved in estimations of the 02 deposits. Also, the determinations of 02 consumption are somewhat uncertain. The value given for the seal, for instance, appears very high. In spite of these reservations, the estimates are believed to be conservative. The information in Table 5 together with that of Table I shows that the diving vertebrates are able to stay submerged from 2 to 4 times longer than their O2 would last if the resting metabolic rate remained unchanged. It has already been pointed out that this led Bohr (20) to believe that anaerobic processesmake up for the depression of aerobic metabolism, whereas Richet (I I 2) held the view that the total energy metabolism is reduced during diving. Decisive experiments have not been performed until relatively recently. Scholander (I I 7) made continuous measurements of the 02 consumption before and after diving. He showed, in seals and ducks, that the excess intake of oxygen after a prolonged, quiet, and restrained dive was much less than one would have expected. This was found to be true also in the manatee (I 23) and the alligator (5). Direct temperature measurements also indicated a decreased metabolism in the seal during diving (I 25). However, the experiments were performed with the subject completely immersed in water, and since the heat loss to water at 25 C is roughly 20 times that to air, these measurements may not reflect metabolic changes only. More recently it has been shown that ducks suffer a marked fall in body temperature when only the head is immersed into water. Changes in the peripheral circulation estimated by means of a hot-wire anemometer indicated simultaneous improvement in the insulation. A general decrease in body temperature concomitant with an increase in peripheral insulation is possible only if the total energy metabolism is lowered (3). Also, in ducks and alligators the rate at which 02 is consumed toward the end of prolonged dives may fall to less than 5 % of the prediving value (3, 5). Decreased metabolism has been reported also in submerged frogs [Rana escdenta (I oo)] and toads [Bufo bufo (87)]. All these findings support the opinion expressed by Richet (I 12).
TABLE 5. Total O2 stored in lung air, blood, and muscles Ofcertain diving animals compared with resting metabolic rate* Animal Available 02, ml

Duck Penguin Seal Porpoise Fin whale Bottlenose



IogO 3350 1 109 1

22 100 250 450 200 l/min 3-4 I/min

4 3 6 3


* Refs. 4, 1~2, II7. t This figure includes 02 of lung air and blood only.

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Eliassen (33) has taken exception to the idea of a decrease in the metabolic rate during diving. His argument is based on experimental dives lasting only 600 I 50 set and on the fallacious concept,that we can consider it reasonable that if the metabolic rate is reduced during diving, this must refer to dives of both normal [I -2 minutes] and prolonged duration. Moreover, Eliassen tends to look at the decrease in metabolic rate from a teleological point of view: it [reduced metabolism] is of a rather doubtful value as a physiological mechanism making animals fit for prolonged dives and (the physiological meaning of such an adaptation to diving condition is rather doubtful. However, the metabolic decrease is not an adaptation to diving at all, but most likely a consequence of cardiovascular adjustments that develop during the initial period of a long submersion. These modifications serve to distribute the circulating blood to the brain and the heart, whereas organs and tissues not so easily injured by hypoxia receive little or no blood while diving. The cardiovascular changes are reviewed on p. 223. F. CO2 Sensitivity of Res#ration Haldane and Priestly (46) showed that the respiratory centre [in man] is exquisitely sensitive to any rise in the alveolar CO2 pressure; a rise of 0.2 % of an atmosphere in the alveolar CO2 pressure being for instance, sufficient to double the amount of alveolar ventilation during rest. The respiratory mechanisms of many other terrestrial vertebrates have been shown also to be very responsive to elevated COZ. For this reason, the ability of the divers to remain submerged for extended periods of time becomes curious in a second dimension. When studying the literature pertaining to CO2 sensitivity of respiration in vertebrate divers one sometimes suspects a gratuitous assumption on the part of authors that the regulatory mechanisms are insensitive to carbon dioxide. Many studies have been carried out with diving reptiles (26, 73), birds (48, g8), and mammals (58, 67) in which the CO2 sensitivity of the respiration has been investigated or commented on. Frequently the animals have been anesthetized or decerebrated (58, 67, 98). Usually 5-20 % CO2 has been given in the inspired air, although in one instance even 25, 50, or IOO % CO2 was inhaled by the subjects (73). As a rule, the effects have been recorded as changes in respiratory rate and amplitude (98) or results have been given as subjective observations only (58,67, 73). Inhalation of high CO2 concentrations have been observed to cause intermittent periods of apnea in ducks (g8), whereas in seals, muskrats, and beavers no changes or only slight enhancements of respiration were observed (58, 67) Experimental data of this sort have led the workers to state or imply that insensitivity to CO2 or inhibition of respiration by CO2 are normal characteristics in the vertebrate divers. Provided that the content of CO2 in the lungs might ever increase to such high values during diving, this conclusion would have been correct. However, analyses of pulmonary gas from alligators have shown the CO:! concentrations to be well below IO % after almost 2 hr of submersion at about 25 C (5). Similarly, the lungs and air sacs of ducks have never been observed to contain as much as IO % CO2 even toward the end of maximal dives. Only when ducks were subjected in rapid succession to two dives lasting for I 2 and IO min respectively did the amount of CO1 in lungs and




air sacs rise to about IO % (3, 4). Rebreathing-dives in seals never caused the pulmonary CO2 concentration to exceed IO % (I I 7). Therefore, the natural CO2 sensitivity of diving vertebrates is not elucidated by studying the respiratory responses to IO % or more of COZ. Likewise, the chemical drive imposed on the respiratory system during prolonged submersions is not to be evaluated from this kind of information. There are reports in the earlier literature that CO2 stimulates respiration in ducks (30) and alligators (I 03). The first paper is incomplete because the workers did not know how much CO2 they added to the air sac system or the arterial blood. The second paper, like other previous reports, deals with changes in respiratory rate and amplitude only. However, the authors found these parameters to increase in proportion to the amount of CO2 breathed. Both papers appear to be little known, and the concept that respiration in vertebrate divers is insensitive to CO2 has prevailed until present times. Recently, the question has been re-examined in the seal (I 13) and in the duck (13). In both studies conscious animals were used and the respiratory minute volume was taken as a measure of the respiratory response to COZ. Robin et al. (I I 3) compared the ventilatory response in the seal (Phoca vituha) and man when breathing 4, 6, or IO % CO2 in 02. They determined the partial pressure of CO2 in the arterial blood (PAco~> and showed the ventilation to increase much more in man than in seal when PACO~ was elevated. However, the respiratory minute volume increased in every one of the seals over the whole range of PACOJS studied (40-80 mm Hg). On the average, ventilation was doubled when the PACO~ was raised from 50 to 70 mm Hg. Andersen and L$v$ (13) made ducks breathe gas mixtures containing 20 % 02 and 0-15 % CO2 in N2. The respiratory minute volume increased in every individual. When the concentration of CO2 inhaled was more than 6 ~01%) the ventilation started decreasing in one of the ducks. The other ducks, on the average, doubled their respiratory minute volume when breathing gas containing 7.5 % COS. These two studies show the respiratory response of the divers to be less than that of man and terrestrial animals in general. However, they leave no doubt that CO2 stimulates respiration in seals and ducks over the range of hypercapnia experienced during the submergence. It is incorrect, therefore, to state that diving mammals are insensitive to COZ, and the assertion that CO2 inhibits respiration in avian divers but stimulates respiration in terrestrial birds (I 15) is entirely wrong.
G. Res~iratoty Resfionses to Lack of O2

Observations on the respiratory effects of hypoxia in diving vertebrates are few. It has been reported that inhalation of gas containing less than IO % 02 produces large increases in the respiratory rate of ducks under ether anesthesia (98). The amplitude was somewhat augmented also. The respiratory rate was very much enhanced when 5 % or less 02 was given. In spite of this vigorous response, a low 02 content in the inspired air does not immediately endanger life. In fact, ducks immersed in water for 15 min endure half this period with Iess than 5 % 02 in the lung gas (3).

Afiil 1966 H. Acid-Base Changes




Severe asphyxia is incurred during prolonged submersions, and large amounts of lactic acid are formed in the muscles, although only small amounts appear in the circulating blood during the dive. Upon emersion, however, the blood is flushed with lactate. Changes in blood pH follow the concentration of lactic acid. The picture is qualitatively similar in seals, ducks, and alligators (5, I I 7). Although data on CO2 tension, 02 saturation, lactic acid formation, and pH thus have *been reported in several species, only one attempt to analyze the acidbase status in diving has appeared (I 2). Ducks were subjected to underwater exposure for IO-I 3 min. In this period 02 saturation fell from some 85-90 % to roughly 15%. The pH usually dropped about 0.4 units, and as a rule the concentration of hydrogen ions was at a maximum in the early part of the recovery period. The partial pressure of CO2 (Pco~) increased steadily throughout the period of submersion, sometimes to more than IOO mm Hg, or about 2.5 times the resting level. The total plasma carbon dioxide (total COS), however, rose only during the initial stages of the dive. When the pH had dropped to approximately 7.20, the total CO2 began to decrease so that at the end of a prolonged dive the total COn was frequently below the resting value in spite of a greatly elevated Pcol. This is probably explained by the acidification of the blood. The exact pattern of acid-base changes depends, therefore, in part on the ability of the animal to retain its lactic acid in the muscles during the dive. Upon immersion, vigorous ventilation at a very low pH causes a rapid drop in bicarbonate. The concentration of HCO,- may fall as much as 15 meq/l in 2 min. The complete cycle of variations in the acid-base status before, during, and after diving can be divided into three stages: I) initially during the dive, pure respiratory acidosis; 2) later in the submersion period, combined respiratory and metabolic acidosis; which develops into 3) pure metabolic acidosis in the early postdiving period.

A. Badycardia

Berts report (I 7) that ducks develop a pronounced bradycardia during sub.mersion has been confirmed in every diving vertebrate investigated (5, 18, 33, 34, 44, 47, 62, 68, 77, 93, gg, I I 7, 123, 135). It has been observed also in nondivers and in man on submergence (60, 65, 73, 89, 96, 97, 122, 123, 137-r 39). Seals well accustomed to the experimental procedure exhibit a fully developed diving bradycardia instantaneously on descent (I I r>, but in other diving vertebrates the heart rate slows down gradually. This is true also in less welltrained seals (63). However, the bradycardia begins to develop immediately on water immersion in all natural divers.. Eliassen (33) has reported that bradycar&a is maximal on submersion in shags [PhaZacrocorax aristotelis (L.)], guillemots [Uris aalge (Pont.)], and black guillemots [Uris g$Ze (L.)]. However, many of



Volume 46

his recordings show a marked initial drop in the heart rate followed by a continued and gradual cardiac retardation. The diving bradycardia is more extreme in adult seals than in pups (47) and also develops more rapidly; young seals are known not to tolerate prolonged diving as well as adults (47, I I 7). Training is an important factor for successful endurance of prolonged diving in ducks as well as in seals (I IO). The rate and extent of cardiac slowing differ in a given species depending on whether the subject is forcibly immersed into water or swims and dives freely. Usually in the alligator the heart rate slows down more abruptly, but then remains steady at a higher level in the free dives (5). On the contrary, in the seal (Phoca vitdina) it has been reported that the diving bradycardia in unrestrained subjects is more pronounced than when the animals are forcibly submerged (98). There is general agreement among authors that the diving bradycardia in reptiles, birds, and mammals results from vagal inhibition, since the response is abolished by vagotomy (5, I 4, 47, 89, 93). Likewise, atropine prevents cardiac retardation during submersion, as was first shown by Richet in ducks (I og). The heart rate decreases in submerged W amphibians as well. It has been reported recently, however, that the diving bradycardia is not due to vagal inhibition in the frog (Rana temporaria) (77). Upon submersion of bilaterally vagotomized animals, the cardiac frequency fell to the same low level as in the intact control frogs. The difference between the prediving heart rate and the diving bradycardia was less in vagotomized frogs than in normal animals, since bilateral vagotomy caused a fall in the heart rate. These two observations are strange, the latter especially so, for section of the vagi generally produces cardioacceleration (go). Jones and Shelton (77) used frogs lightly anesthetized with an agent (Sandoz MS222) that has an accelerating effect on fish hearts (127), and they imply that a similar effect may be present also in frogs. This makes their recordings of a low prediving heart rate in lightly anesthetized, vagotomized frogs even more curious. The ability of their preparations to develop a marked bradycardia during diving was tentatively explained as due to a decrease in sympathetic tone. The authors remark, however, that such a possibility is not well supported by existing evidence. As an alternative explanation they suggest that the bradycardia is an asphyxic effect on the heart directly. Because diving bradycardia appears to be elicited by vagal inhibition of the heart in all higher vertebrates, the finding in the frog is intriguing, since this animal presumably has developed all nervous structures necessary for parasympathetic inhibition of the heart. Indeed, the cardiac effect of vagal stimulation was discovered and worked out in detail in the frog. Diving bradycardia is due to prolongation of the diastole; the electrocardiogram (ECG) is thus characterized by a very marked increase of the T-Q interval. Other prominent changes in the ECG include progressive lengthening of the P-R interval with eventual disappearance of the P-wave. The T-wave is usually elevated and peaked; sometimes it appears diphasic or inverted. The vagal cause of these changes has been suggested by several workers. For example, it has been demonstrated that similar changes are produced by administration of physostig-

April 1966




mine in semiaquatic snakes (73). The ECG changes also suggest hyperkalemia, and it has been shown that the concentration of potassium in plasma may increase as much as threefold in ducks during submersions lasting for 8 min (I 0). The nervous influence, however, seems by far the more important, for the P-wave reapqears on emersion in spite of maximally elevated plasma potassium, and the P-R interval is shortened in correspondence with the postdiving tachycardia. The T-wave, on the other hand, remains elevated and peaked for several minutes. At times, especially in the earlier literature, diving bradycardia has been regarded as a prime and independent adjustment to submersion rather than as an element in a series of controlled cardiovascular changes. But now most authors have realized that the cardiac slowing is only one aspect of a general circulatory adjustment, although some current papers still report exclusively on the diving bradycardia. At present, a picture is emerging that in all essentials substantiates the physiological responses Irving envisioned more than 30 years ago. The clarification has come because observations and evaluations of the functional significance of the diving bradycardia have motivated studies of pressure, flow, and other cardiovascular relationships. These experiments are now reviewed chronologically, with a few necessary digressions.
B. Blood Pressure

The relationship between the degree of cardiac retardation and the period of underwater exposure endured by seals was studied by Irving et al. (63). They found that the earlier the diving bradycardia develops, the longer the animal is able to extend its sources of 02. This, they subsequently pointed out, does not mean that the decrease in 02 consumption simply depends on the heart rate (44). Obviously, the heart itself will consume less 02 if its frequency is suddenly reduced by some go%, but even if the bradycardia contributes substantially to saving 02 on the part of the heart, this does not explain a prolonged extension of the limited 02 deposits. Further research revealed that the arterial blood pressure as measured in the femoral artery is rather well maintained in the seal in spite of the low heart rate (64). The mean level of arterial blood pressure was practically unaltered before and after diving. Also, they observed that the diastolic limb of the pressure curve descended gradually in submerged seals, not abruptly as when breathing air. At the end of such a diastolic pause the blood pressure was still about IOO mm Hg, only slightly lower than in the pre- and postdiving periods. They interpreted the gradual fall in arterial blood pressure during cardiac diastole to indicate that the rate of emptying of the large arteries slows down during diving: In fact, the rate of emptying of the arteries appeared to diminish about in proportion as the frequency of the heart decreased, with the result that the mean pressure remained normal even during the long diastolic pauses. In addition, they found that small peripheral arteries were completely occluded during diving. Irving et al. dismissed the possibility that a tenfold increase in the stroke volume would compensate for the bradycardia and explain the slow descent of diastolic



Volume 46

pressure, and they concluded that normally a large part of the peripheral circulation is probably restricted as a unit when the heart sIows. This increase in peripheral resistance, they asserted, compensates for the extreme bradycardia. In recent years the regulation of blood pressure has been extensively studied in avian divers (49, 75, 76). Blood pressure in the femoral artery during 3-min dives was recorded by Johansen and Krog (76). They reported that the mean arterial pressure did not change appreciably during short dives (30 set) in spite of bradycardia. In prolonged dives (3 min) their published recording shows a systolic pressure about 20 % below the prediving value; the diastolic pressure apparently fell to 50% of the control level and the pulse pressure was correspondingly elevated. These changes caused the mean arterial pressure to diminish by as much as 25 %. To describe such reductions in pressure by the term somewhat lowered seems inadequate. Similar variations have been shown to take place also in the alligator (5). This poiktiothermic diver, however, does not maintain the pressure in the femoral artery even as effectively as does the duck during submersion. After an initial increase, both systolic and diastolic pressures of the alligator fell throughout the dive, although the pulse pressure either remained close to the prediving value or was elevated. More recently the ducks arterial blood pressure in diving has been studied by Hollenberg and Uvngs (49). Recording from the brachial or sciatic artery, they found in 38 of 40 ducks that the mean pressure increased on the average 17 % during submergence. They also show a record in which this increase amounted to almost 44 % I min after water immersion. Only two ducks exhibited a falling blood pressure during diving. It is important to note that all dives reported were relatively short ones lasting only r-2 min. Several of their records show a beginning fall in blood pressure after the initial rise. Johansen and Aakhus (75) have re-examined the regulation of arterial blood pressure in a fine study on central cardiovascular responses in diving ducks. They report a fall in aortic pressure even during dives lasting 40-60 sec. The systolic pressure fell approximately I o % from I 80 to 160 mm Hg, whereas the diastolic diminished by 45 % from 135 to 75 mm Hg. However, they observe that although these results are fairly typical the actual pressure levels displayed during diving could vary a great deal. In some experiments there was no change in systolic pressure at all and only a slight reduction in diastolic pressure. At other times a rise in the systolic pressure values occurred; the pressure increase showed up gradually and in no experiments was an initial marked pressure rise detectable. Just recently, data have become available on systemic and pulmocutaneous pressures in frogs (Ram pZpze?zs, Ram temporaria). The arterial blood pressures have been found to fall in the submerged animal by 20-25 %, the systolic somewhat more than the diastolic, the pulse pressure thus being kept at a fairly uniform level before and during diving (I 26). Summing up the information pertaining to regulation of arterial blood pressure, certain points seem well established: it is quite clear that the mean arterial blood pressure decreases appreciably in prolonged submersions. This is true for the

April zg66




seal, duck, alligator, and frog. Usually, the reduction in diastolic pressure is much more pronounced than the fall in systolic pressure. As a result the pulse pressure is sustained or increased during long dives. It is quite remarkable that the homeothermic divers are able to maintain a fairly high level of arterial blood pressure during prolonged dives. Poikilothermic divers are not able to regulate their blood pressure as well when submerged. In short dives lasting only 30-60 set, the findings are in disagreement. Hollenberg and Uvnas (49) have reported that the diving bradycardia is typically accompanied by a marked pressor response. Johansen and Krog (76), on the other hand, have made no such comment, and the recordings reproduced in their paper shows no rise in the arterial blood pressure during submersion. Johansen and Aakhus (75) have emphasized that they never observed elevated blood pressure during the initial stages of submersion. Eliassen also (33) found that the pressures in the ascending aorta, the brachiocephalic artery, the pulmonary artery, and the pulmonary vein remained virtually unchanged or increased very slightly in diving birds. There is at the present time no way of knowing the cause of these differences. They may reflect individual variations in the subjects; they could result also from differences in experimental procedure or conditions. These variations should be kept in mind, however, since they are important for our discussion of the nervous regulation of the cardiovascular responses to diving (P* 234. C. Cardiac Outfit Since the cardiac output equals stroke volume times heart rate, significant changes in the cardiac output are to be expected during diving.. It will be recalled that during diving bradycardia the heart rate may be reduced to onetenth the prediving level (p. 225). Most authors have agreed that a full compensation of the cardiac output by a corresponding increase in the stroke volume is impossible. The stroke volume has not been directly measured as yet in homeothermic divers, but there have been some interesting observations that may be related pending direct evidence. From his recordings of heart rate and blood pressure Eliassen inferred that the cardiac output decreases in proportion to the level of bradycardia in diving birds (33). Johansen and Aakhus (75) measured aortic and intraventricular pressures simultaneously in ducks. They assumed by this procedure they could obtain an indication of ccventricular energy release, and hence stroke volume. This appears reasonable. They also observed that the period of cardiac ejection of blood into aorta remains unaltered before and during diving, concluding that the stroke volume is virtually unchanged. In a later study these same authors studied dimensional changes in central cardiovascular structures by means of angiocardiography (I). They found the size of the heart to increase during submersion and suggested that the end-diastolic volume is not the sole controller of stroke volume in the diving duck. The cardiac output during submergence has been derived from pulmonary



Volume 46

blood flow measurements in an unrestrained sea lion diving spontaneously and on command (34). A pulsed ultrasonic flow transducer was mounted on the pulmonary artery. Phasic blood flow was recorded on magnetic tape, and heart rate, stroke volume, and cardiac output were computed using analogue technique (39, 40). The stroke volume was Zound to remain constant and the cardiac output decreased in proportion to the bradycardia. Shelton and Jones measured the stroke volume in frogs (Rana pz$;ens>and determined the cardiac output (I 26); they reported a decreased stroke volume during submersion. The cardiac output fell to levels between one-half and onefifth of those recorded at the surface. Their recording system involved a moderate extra load on the heart of approximately 50 dynes/min (the reviewers calculation), and required relatively extensive surgery on the animals prior to diving. Light anesthesia was maintained throughout the experiments. Their results agree well with those obtained in higher vertebrate divers, and it seems safe to conclude, therefore, that the cardiac output always decreases during submersion. In warmblooded divers in which the stroke volume does not change appreciably this decrease is due primarily to the bradycardia, whereas in frogs a marked bradycardia and a diminished stroke volume both contribute to reduce the cardiac output. D. Distribution of Circulating Blood The brain and, to a certain extent, the heart are easily and irreparably damaged by severe and protracted hypoxia (15). Most other organs and tissues are far less vulnerable. Survival in prolonged submersion asphyxia, therefore, depends first on the ability to save 02 where it is not urgently needed and reserve it for use where it is indispensible. Second, the limited 02 stores must be fully utilized. Only small quantities of 02 are conserved by the cardiovascular adjustments discussed: however profound the diving bradycardia, it does not in itself extend the O2 deposits of diving vertebrates appreciably. Large-scale preservation of 02 seems possible only if all tissues other than those critically dependent on a continuous supply of this gas participate. This means that a saving of 02 can be achieved during submersion by distributing the circulating blood to the brain and the heart at the expense of tissues and organs less easily injured by hypoxia. Such a response was visualized by Irving (55). He also provided some support for his hypothesis by showing that the blood flow to the brain increases during arrest of breathing while the muscular blood flow simultaneously decreases (57). Much work has been carried out to test this point and to furnish additional evidence on the operation and effectiveness of the mechanism. Muscular bloodflow. Scholander (I I 7) discovered that although the concentration of lactic acid in blood of seals, ducks, and penguins only doubled or tripled during a prolonged dive, it might increase to ten times the prediving value on emersion. He assumed that the lactic acid is formed in the muscles during submersion, retained because of a largely suspended muscular circulation, and

April 1966




finally washed out on ascent. This hypothesis was proved in a later study on seals (s24), where it was shown that a marked increase in muscular lactate concentration took place during diving with no parallel rise in blood lactic acid. On emersion the blood was rapidly charged with lactic acid while the concentration of lactate in the muscles fell. In the same paper it was reported that the oxygen stored in muscles was consumed during the first few minutes of submersion, at which time the arterial blood was still more than half saturated. This is inexplicable if muscular circulation is adequate during diving. The myoglobin, due to its very high affinity for 02, would not be reduced at such an early stage, but would remain oxidized throughout the major part of the dive. Likewise, retention of lactic acid in the muscles during submersion is clearly impossible if the circulation remains unchanged. The lactic acid changes have been verified in the duck (4, 12) and extended to the alligator (5) and snakes (91). Reduced muscular blood flow has been demonstrated in ducks and seals using the thermostromuhr technique (3, 44). Johansen and Krog (76) also observed a decrease in the blood flow to the legs of submerged ducks by showing a decline in the rate of venous pressure rise in a branch of the femoral vein after the main venous return from the limb had been occluded. Since their findings were not supported by simultaneous plethysmography of the limb, the results are questionable because venous pooling may have taken place unnoticed. In fact, it has been objected (49) that Johansen and Krog actually measured venous dilation by their occlusion technique. Hollenberg and Uvnas studied muscular blood flow in submerged ducks using a drop-counter (49). They found no change or a slight increase in the blood flow to the skinned leg with the web tied off. Now, the skinning itself may cause large shifts in muscular blood flow, and whatever changes may take place normally during diving could very well fail to develop in such a preparation because of the injury inflicted. Their results, however, are reconcilable with the data bearing on lactic acid changes and on saturation of myoglobin and hemoglobin, if not easily with those obtained with a hot-wire anemometer. To explain their results completely it seems necessary to postulate extensive shunting in the muscles by way of arteriovenous anastomoses so that the metabolizing parts were excluded from the general circulation. Finally, it is of great interest to review a recent and important paper by Johansen (74) that has provided some much-needed data. He studied the regional distribution of circulating blood in submerged ducks using the radioactive isotope Rb*6 The rate at which Rb*6 is taken up by organs and tissues depends on their extraction coefficients for Rb *$ the arterial concentration of the isotope, and the blood flow through the various tissues (I 16). The advantage of the method is the opportunity to compare the blood flow to all different organ systems in any one subject. The, chief disadvantage is that only qualitative data are obtainable. The isotope was injected intravenously as Rb*Cl when a diving bradycardia of 15 beats/min had been established. Two minutes later the heart was stopped by injecting a saturated KC1 solution. Organs and tissues were dissected out and compared with control values. Johansen reports that the large masses of skeletal



Volume 46

muscles such as the pectoral, the gastrocnemius, and the neck muscles showed no or a very slight radioactivity only, which indicates that these tissues had been effectively excluded from the circulation. The activity in the masseter, certain other muscles in the head, and the esophagus presented higher activities in the submerged animals than in the controls. Likewise, the eye displayed a high activity when excised from a submerged duck. These parts of the organism are presumably put to work in the duck when it searches for food and feeds at the bottom of shallow waters. The results are noteworthy, therefore, in showing that the central nervous system is not limited to an on-off response in controlling blood flow to the various parts of the body during submersion, but rather is discriminating in its ability to distribute blood to any subsystem of the organism on a segmental basis. Such a capacity for fine regulation has been suggested in the past (Landgren, personal communication), and Johansens data confirm this for the first time. Also, certain other organs and tissues that normally are in functional operation in the submerged duck exhibited higher activities when excised from the immersed animal than when taken from the controls. (These findings are cited in the appropriate context.) If the situation is similar in the seal, it is tempting at this point to offer a suggestion on the significance of the seals high deposits of 02 in the myoglobin: since the seal is carnivorous and hunts for food, its skeletal muscles are very active when pursuing prey. Our best evidence indicates, as we have seen, thatthe large muscle masses are noncirculated in a dive since they otherwise would take a heavy toll of the 02 deposits. However, the muscles carry their own supply of 02, which is confined to this tissue. Presumably this amount of 02 is sufficient for short bursts of activity between periods of breathing. This appears to be borne out in the hunting behavior of seals; if a pursuit fails they do not prolong such a dive, but surface and restore their 02 deposits before making a second try. Coronary blood flow. Myocardial blood flow has been estimated only by Johansen using the radioisotope technique previously discussed. Markedly elevated levels of activity were found in hearts of submerged ducks. It seems, therefore, that the heart is well supplied with blood during diving. Gastrointestinal blood flow. The first observation on changes in gastrointestinal blood flow was reported by Irving et al. (64). They exposed a part of the small intestine in the seal for visual inspection. A gradual vasoconstriction was observed to take place in the small arteries. Shortly after submersion the intestine had turned cyanotic. Intestinal blood flow has also been recorded using a drop-counter to operate an ordinate plotter (49). A very marked decrease in the circulation was observed -in fact, zero flow was seen in one of the subjects. Johansens studies using Rb86 also include data on gastrointestinal blood flow. He found the activity in the esophagus increased in submerged ducks, whereas that of the gizzard and the intestine fell. Skin blood flow. Reduced circulation in the skin was first suggested by Scho-

April zg66




lander (I IT), who noticed profuse bleeding from supeficial incisions before or after diving. During submersion, however, the wound sometimes did not bleed at all. Hollenberg and Uvnas (49) used brachial arterial or venous blood flow to represent skin flow. In this case the drop chambers were inserted distal to the origin of the well developed proximal musculature, and the greater part of the distal wing musculature was tied off. In this preparation they recorded a marked decrease in circulation during diving. Johansen (74) also investigated skin blood flow with the radioactive tracer RbY The results obtained varied in that the skin from the head region showed increased activity during submersion, whereas skin from the thorax yielded just the background count. He concluded that the main part of the skin is probably noncirculated in the diving animal. He also reports that if the bird was subjected to a heat stress the web would remain vasodilated during diving. Thus, as far as the blood flow to the skin goes, the usual vasoconstrictor reflex may be modified in the submerged animal if other circumstances necessitate such a shift. In the frog, of course, conditions are reversed. Here the skin blood flow increases during diving in order to make full use of the cutaneous respiration. Such a change in the circulation is adequate to meet the requirements for O2 over environmental temperatures up to 20 C in Rana escuknta (gg, 100). Renal circtllation. Renal ischemia with impaired glomerular filtration rate and a fall in the effective renal plasma flow during diving was reported in seals (2 I). More recently a complete cessation of renal function has been observed in trained seals (92). The radioisotope experiments in ducks (74) also showed a conspicuous reduction in renal blood flow. It seems safe to conclude, therefore, that the kidneys are poorly supplied with blood in submerged animals. Glandular circulation. Only Johansens data (74) are available; they showed pancreatic circulation to be completely checked. The liver received about the same amount of blood in diving and nondiving subjects, as judged from the counts. Both the thyroid and the adrenals had higher ,activity in the submerged duck than during air-breathing. The increase in the adrenal blood flow was especially noteworthy. The levels of corticosteroids or catecholamines in divers have not been studied as yet. The presumably high rate of blood flow through the gland in water-immersed divers is interesting and makes such a study attractive. For instance, this observation may mean that the cardiovascular responses are controlled by an interplay between nervous and endocrine factors. Knowledge of how humoral and nervous factors share the responsibility for a successfully integrated cardiovascular response to underwater conditions is much needed. Brain circulation. Most authors allege that the brain receives an ample supply of oxygen during diving because the divers emerge from prolonged underwater exposures with no visible motor disturbances or other symptoms of organic damage. Direct measurements of cerebral blood flaw in divers are not available. This may explain the remarkable harmony among investigators. A qualitative estimate




of cerebral blood flow during diving may be obtained from Johansens experiments with Rb89 However, the method is not very attractive when used for evaluation of blood flow in the brain, since the brain has such a small extraction ratio for Rba6 that one cannot compare the cerebral blood flow to flow in other organs and tissues in the same animal. Johansen solved this difficulty by studying the brain counts in two groups of subjects, one submerged while the other continued to breathe air. The results indicated a threefold increase in cerebral circulation during submersion over that in the air-breathing bird. Conclusion. Oxygen depots of vertebrate divers are inadequate for an aerobic metabolism at the resting, air-breathing rate. Their ability to perform prolonged underwater exposure depends on a widespread peripheral vasoconstriction that involves most vascular beds: most of the muscle masses, the main part of the skin, the gastrointestinal system (except the esophagus), the renal circulation, and most glands. In this way a diving animal virtually becomes a heart-lungbrain preparation, [Van Slyke, quoted by Elsner and Scholander (35)] and thereby reserves the limited oxygen stores for the parts of the body where it is urgently needed. The general vasoconstriction permits the animals to maintain a fairly high level of arterial blood pressure, and the pronounced and sudden changes in flow and pressure relationships are compensated by a marked bradycardia.

Nervous mechanisms that evoke and control the respiratory and cardiovascular adjustments to diving have been much less studied than the responses themselves. It would be incorrect, however, to say that the nervous mechanisms have attracted little attention. Contemplation of how the physiological changes during diving are brought about is implicit in the experimentation and writings of Richet (108-1 IQ), Huxley (5~54), and Lombroso (8g), and the problem was emphatically expressed by Irving (55). Obviously, rational inquiry into nervous control of physiological responses to submersion entails reliable information of the adjustments proper. Recent advances in our knowledge of the functional changes elicited on submersion have served to mature the problem of how these 02 conserving reflexes are activated. Evidently several workers have entertained similar ideas concomitantly, for it is interesting to note that the first modern studies to deal with the activation and development of the physiological responses to diving were carried out concurrently but independently in three different Swedish institutions, and the reports (6-8, 37, 49) appeared in the same journal within 6 months. Domestic ducks were used in all of these studies. Three of the papers (6, 7, 37) describe experiments designed to separate effects of asphyxia versus water immersion per se. In all three investigations the diving bradycardia WaSU!daS was used as an index of the cardiovascular changes elicited on submersion. In order to separate the responses to asphyxia from those caused by immersion into water the ducks were provided with tracheal cannulas that bY





could be attached to respiratory pumps for artificial ventilation. Also, the tracheal cannulas could be extended out of water to give the subjects free access to air while submerged. Feigl and Folkow (37) found that the bradycardia of submersion is not caused simply by asphyxia. When asphyxia was produced by occluding the tracheal cannula, cardiac retardation was less obvious compared with the normal development of diving bradycardia. Moreover, they observed that when a duck had been -submerged until a normal diving bradycardia was established, and its head was then raised, the heart rate returned to the prediving level as soon as breathing was resumed. If the trachea was obstructed during submersion and surfacing, however, the heart would accelerate on ascent, but only to about 75 % of the prediving level. The fall in heart rate in submerged ducks that were artificially ventilated was conspicuous and immediate, but it was not as pronounced as that normally seen during submersion. Finally, using gas mixtures made to produce hypoxia or hypercapnia respectively, Feigl and Folkow found hypercapnia to potentiate the initial water immersion bradycardia more markedly than hypoxia. They concluded that the diving bradycardia depends on at least three factors: I) a specific nervous reflex resulting from submersion of the head, 2) the progressive hypercapnia, and 3) the increasing hypoxia. My own experiments (6, 7) were carried out using essentially the same technique, and the findings were very similar. Only a few points need to be added. Observations of the heart rate when the beak and the head of the duck were immersed in water to different levels indicated that the diving bradycardia was precipitated by water immersion of the area around the nostrils and the nasal cavity (6). Positive-pressure ventilation of lungs and air sacs in submerged ducks showed that the diving bradycardia could be modified when the respirator was adjusted to deliver large tidal volumes. In fact, the bradycardia could be turned into tachycardia and the bird made to attempt to breathe spontaneously if large volumes of air were administered with each stroke of the pump. However, as long as near-normal tidal volumes of gas were delivered at a normal rate, such responses could not be obtained regardless of the composition of the gas mixture used. Asphyxia produced by occlusion of the tracheal cannula caused cardiac slowing 3040 set after the airway had become obstructed. This bradycardia appeared abruptly, but it was not as pronounced as that seen during diving. Asphyxia alone was never observed to cause apnea (7). In a subsequent study (8) it was shown that the physiological adjustments to diving are medullary reflexes: decerebrated subjects exhibited apnea and bradycardia on water immersion as readily as before decerebration. These responses were obliterated by bilateral section of the trigeminal nerve. Birds completely deprived of sensory information from the trigeminal area would continue to breathe through the tracheal cannula during water immersion with no change in the heart rate whether or not the central nervous system had been left intact. An analysis of the various subdivisions of the trigeminal nerve showed



Volume 46

the ophthalmic branch to be the most important limb in the afferent pathway. It is of interest to note that subjects with intact central nervous systems, but deprived of sensory messages from the trigeminal area, were panic-stricken when submerged. (This is the typical response to submersion in nondiving animals, whereas natural divers relax when immersed into water.) Also, such preparations appeared to test the possibility to resume breathing by way of the tracheal cannula. However, they never ran the risk of assuring themselves that breathing would have been perfectly safe. Instead they struggled in violent, rhythmic bursts that coincided with their halfhearted respiratory efforts. The struggling and attempts at breathing looked very much like voluntary breath-holding. It was concluded that the nervous impulses that presumably arise in the area in and around the nasal cavity on water immersion inhibit the respiratory center and, directly or indirectly, elicit the cardiovascular responses to diving. Reite et al. (107) have reported that they were unable to detect any effect of water immersion on the heart rate when submerging ducks that were artificially ventilated with air. Their paper gives no information about the frequency and the tidal volume with which the subjects were ventilated. Since the cardiac response in such preparations is a function of these parameters (7), it is possible that they over-ventilated their ducks. In conclusion these authors offered the suggestion that receptors sensitive to mechanical distortion located within the thoracic cavity or in the respiratory musculature proper are important in the development of the bradycardia during submersion asphyxia. This statement is in agreement with ideas held by other investigators. The possibility has been discussed in some detail already (6,~). Hollenberg and Uvnas (49) studied circulatory responses to diving in ducks before and after denervation of carotid chemo- and baroreceptors. For technical reasons they found it impossible to denervate these structures separately. The operations obliterated the diving bradycardia, as well as the pressor response they usually observed in their experiments with intact subjects. They concluded that progressive asphyxia acting by way of chemoreceptor stimulation produces an increase in peripheral resistance and an early and progressive fall in heart rate. In arriving at this conclusion Hollenberg and Uvnas recalled the observation that baroreceptors are insensitive to changes in pH, Pcoz, and Pas (36) and found it likely that the abolition of the characteristic circulatory response to asphyxia after their [baroreceptors and chemoreceptors] denervation was due to loss of the chemoreceptors. Johansen and Aakhus (75) also commented on baroreceptor activity as a possible cause of diving bradycardia. In contrast to Hollenberg and Uvn%s (4g), they never observed elevated blood pressure during the initial stage of submersion. This, they asserted, is important in denying the bradycardia as a result of increased baroreceptor activity. Their records show that bradycardia developed with no concomitant rise in arterial blood pressure. However, this does not eliminate the possibility that baroreceptors determine the rate of cardiac slowing, since information from the baroreceptors presumably serves to prevent changes

April 1966




in the arterial blood pressure. The baroreceptors are rate-sensitive, i.e. their firing rate is determined by the rate of change of blood pressure (83). The system for blood pressure regulation thus includes facilities for quick response and possibly overcompensation* (82), in addition, probably, to the stability provided by proportional control *. Another feature of the regulator seems to be automatic reset control6 (45). Subtle performance of such a control system would eliminate large pressure changes in an intact diving animal as long as the volume of circulating blood is in reasonable proportion to the vascular beds being circulated. In fact, when the heart rate starts to slow down in a homeothermic, vertebrate diver, vasoconstriction may have been initiated already by the water immersion per se, the increasing asphyxia, or both. As peripheral vasoconstriction progresses, any slight rise in blood pressure is automatically compensated by further cardiac retardation. In the end when peripheral vasoconstriction has become fully developed, bradycardia is maximal and the blood pressure has not shown any appreciable changes. Such exquisite regulation is not detectable by the methods used by Johansen and Aakhus (75). It is my opinion that dismissal of the baroreceptors as the cause of diving bradycardia is premature. Finally, Feigl and Folkow (37) have reported that diving-like responses can be produced by electric stimulation in the mesencephalon. This is an interesting observation that must be left without additional comments, but ought to stimulate further research. Cotzctusion. A start has been made in determining which nervous mechanisms are responsible for eliciting and maintaining the physiological adjustments to diving. The experiments of Feigl and Folkow (37) and Andersen (6-8) indicate
3 Rate control is expressed mathematically Y as follows:

YO = --ar (dp/dt) factor, dp/dt = rate of change of pres-

where: Y - YO = e&&or response, ac = proportionality sure. 4 Proportional control may be defined Yg Yo = 45

- PO)

where: Pt = pressure at any instant, PO = set point for pressure, Pt - PO = error signal, a = proportionality constant, Yr = controller output for Pt condition, YO = controller output for set point (PO) condition. 6 Automatic reset control (floating control or integral control) in a linear system is expressed dY/dt where: dY/dt = output of controller, Integration gives = #(P - PO)

a = rate


measured deviation.


t J

(P - Po)dt

For a further discussion of control theory and applications in biological systems see: Physiological Controls and Regulattons, edited by W. S. Yamamoto and J. R. Brobeck. Philadelphia: W. B. Saunders, 1965. (See also re&. 45 and 82.)



Volume 46

that water immersion per se is a chief factor in eliciting these oxygen-conserving reflexes. Especially the finding (8) that interruption of the trigeminal pathway obliterates such reflexes strongly supports this point of view. The role played by the trigeminal impulses, which presumably arise from the area of the nostrils on submersion, may be mainly to inhibit the respiratory center. However, they may precipitate the cardiovascular adjustments as well, either by direct action or indirectly via their effect on the respiratory center. Asphyxia certainly influences the heart rate in diving vertebrates. The question is whether asphyxia is an evocative factor in triggering the circulatory responses (4g), or whether asphyxia merely sustains and reinforces adjustments that have already been produced by water immersion (6, 7, 37). At present the question may be left open. The degree to which the lungs and air sacs are inflated at the beginning of a dive seems to determine successful development of the cardiovascular reflexes. This has been observed by Eliassen (33), Andersen (6, 7), and Reite et al. (107). However, impulses arising from mechanoreceptors in the respiratory musculature can ha dly elicit the diving responses. It remains to be learned whether the nervous impulses elicited from the peripheral trigeminal area act directly on the vasomotor center as well as the respiratory center, or whether the action on the former is indirect. The nature of the receptors themselves is also unknown. A cue may be that diving birds are equipped with specially daerentiated receptors, the so-called Herbst or Grandry corpuscles, on the beak, especially in the region of the nostrils. These receptors resemble to some extent the Meissner and Pacinian corpuscles. Their functional characteristics are unknown, but they are supposed to be tactile receptorcs (19).


A. Human Divers A marked bradycardia takes place in man during submersion (24, 60, 62, 96, 97, 122, 138, 139). The same effect may be produced also when a subject is commanded to submerge his face only (I 19, I 37). The bradycardia is equally pronounced in good and poor swimmers (I 19, I 37). Craig (24) has reported that cardiac retardation is seen on submersion in children as well as in adults; it appeared to be independent of depth. Irving (60), in presenting the experimental evidence for the original report of the phenomenon (62), stated that the bradycardia persists in spite of vigorous exercise just as is the case in the diving vertebrates. This has been confirmed by Scholander et al. (I 22) and Olsen et al. (g6), but contradicted by Craig (24). It may be worth noting, however, that Craigs subject breathed IOO % 02 for 5 min prior to descent, and that his data were obtained in one experiment in one subject. The diving bradycardia in man is less

Apnl .zg66




predictable than in naturally diving animals. It may also be easily modified if the subject is stressed, frightened, or harassed (I 37). The most prominent and consistent EGG changes seen in diving men were sinus bradycardia and arrhythmia; sinus arrest with subsequent nodal or ventricular escape; A-V block, A-V nodal rhythm, and idioventricular rhythm. Equally typical were alterations in configuration and amplitude of the P-wave, which generally diminished, and the T-wave, which became peaked and elevated (96). Similar changes take place in the natural divers (p. 224) and may be due to hyperkalemia. Subjects accustomed to underwater conditions have been particularly well studied with respect to their responses to diving. Pearl divers from the Torres Strait archipelago were studied by Scholander et al. (122). Their subjects displayed marked bradycardia during 60-90 set of submersion. The blood pressure, measured in the bra&al artery, was maintained or tended to increase slightly in spite of the cardiac retardation. The lactic acid concentration in venous blood changed in the same way as in the natural divers, with little or no increase during submersion followed by a definite elevation on surfacing. Similar investigations have been carried out on American skin divers used to underwater work employing self-contained, underwater-breathing apparatus, but who were also able to perform apneic diving for as much as 3 min at rest and I .5 min with exercise (97). The results were essentially identical to those obtained from the pearl divers. Thus, the cardiovascular adjustments that are so conspicuously developed in diving vertebrates are present also in diving man, although not to such a marked degree. Respiration in human divers was first studied approximately 30 years ago in the Japanese diving woman (ama) by Teruoka (I 29). Recently his findings have been confirmed and the whole subject much extended in the Korean diving woman (50, 78, 128). The ama may dive as deep as 15-20 m for 60-80 sec. More typically, however, the Korean ama dives to about 5 m for 30 set and averages 60 dives/hr. They hyperventilate slightly before descent to bring the Pcos down to about 28 mm Hg. Upon submersion their lungs are filled to 85 % of vital capacity. Due to compression at the bottom both 02 and CO2 are removed from the lungs by the circulating blood. On ascent CO2 diffuses from the blood to the lungs. Simultaneously the 02 pressure may drop rapidly to as little as 25 mm Hg (50.) The vital capacity in the ama was found to be larger than in nondiving women. This was due to their higher inspiratory capacity. The residual volume and the expiratory reserve volume were not significantly different in the amas and the controls. The maximal breathing capacity of the ama was roughly 15 % higher than in the nondivers. Also, the ventilator-y response of the ama to high COz was less than in the controls, whereas no differences were seen in the ventilator-y response-to low 02 (I 28). The basal metabolic rate of the nondiving women agreed with the DuBois standard throughout the year, while that of the ama



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.a1variations, being elevated in the winter (78). All the work on the showed season ama ha.s been summarized and thoroughly reviewed recently (102).
B. Asjdyxiu at Birth

Meticulous studies of arterial 02 saturation, CO2 content, and pH with subsequent calculation of Pcoz and buffer base have shown that fetal asphyxia is inevitable in almost every delivery (72). The severity of the acid-base changes, respiratory acidosis with superimposed metabolic acidosis, was compared with the general condition of the newborn infant, and it was suggested that the degree of acidosis is indicative of the degree of asphyxiation endured by the fetus (72, I 34). Further investigations of the concentrations of lactic acid and potassium in the blood in addition to the parameters already mentioned revealed a postdelivery maximum in the lactic acid concentration with a consequent fall in pH, Pcos, and buffer base (69071). The postdelivery rise in blood lactic acid is acute enough to indicate that the lactate is washed out from a noncirculated deposit. Hyperkalemia is associated with the acidotic condition. Bradycardia is also frequently observed in asphyxiated infants and is usually interpreted as being caused by this condition. Thus, the physiological changes in the human infant strongly suggest that oxygen-conserving reflexes similar to those seen in diving vertebrates operate during delivery.
C. Oxygen-Conserving Reflexes in Disease

Mesenteric vascular insufficiency with consequent intestinal &hernia and necrotic lesions of the gastrointestinal tract have been reported in patients with myocardial infarction, ventricular aneurysm, coronary arteriosclerosis, or coronary o&al stenosis. Gastrointestinal necrosis may follow from mesenteric angiospasm after hemorrhage, traumatic shock, cardiac arrhythmias, surgery, burns, and congestive failure as well (23). It was concluded that the blood is diverted to more vital tissues like the brain and the myocardium. This syndrome of mesenteric vascular insufficiency is basically identical to the physiological adjustments the vertebrate divers employ to survive prolonged submersions (31, 34). Further support for such a mechanism has been reported by Refsum (104-106). He studied patients with severe pulmonary insufficiency and found that an arterial 02 content of about 6 ml/100 ml blood, a Pa of approximately 20 mm Hg, is compatible with both consciousness and survival. This is possible because the high PC- and a low pH simultaneously incurred ensure a high degree of cerebral perfusion and shift the dissociation curve for hemoglobin to the right. Thus, what little O2 is present in the blood will be readily unloaded to the tissues (I 04). However, Refsum found that cellular enzymes such as glutamic oxalacetic transaminase (SGO-T), glutamic pyruvic transaminase (SGP-T), and lactic dehydrogenase (SLDH) appeared in the blood of the patients. Isoenzyme distribution of SLDH indicated

AjviZ 1966




this enzyme to be of hepatic origin (I 05). On autopsy, centrilobular and focal necrosis of the liver was confirmed with no evidence for myocardial derangement (I 05, I 06). It appears that the brain and the heart were maintained in severe hypoxemia whereas the liver may have been largely anoxic. Recently it has been suggested that the circulatory oxygen-conserving reflexes may lead to serious cardiac arrhythmias, cardiac arrest, and sudden death if massively elicited in patients with angina pectoris or myocardial infarction (I 37).

Oxygen shortage presents the vertebrates with a formidable problem. Survival of the entire organism depends on preserving the integrity of that organ most susceptible to irreparable damage from lack of 02. The brain and, to a lesser extent, the heart are highly vulnerable and need to be protected. During respiratory arrest the smallness of the 02 stores within the body necessitate a priority among organs and tissues so as to sustain those easily damaged, at the expense of others that are not less important in physiological function, but tolerate transient hypoxia much better. We have seen how such a mechanism is developed to near perfection in vertebrate divers. However, occasional reference has been made to that fact that other vertebrate animals and man are also able to deal similarly with lack of ox*ygen (23, 5% 57, 59, 69-72, 89, *I& * 9, 1% I 23, I 34, I 37). Phylogenetically these reflexes are old, for they are well known to take place also in different species of fish when they are taken out of water (25, 41, 88, III). Upon examination of our present knowledge of the oxygen-conserving reflexes it seems evident that they are present in ah vertebrate organisms during all stages of life. However, because the habitat in which the diving vertebrate dwells is adverse as far as air breathing goes, these mechanisms are constantly called into action to ensure successful endurance. Consequently, in the natural divers we observe the 02.saving adjustments operating at a very high degree of precision. It is concluded, therefore, that the physiological adjustments seen in diving are not defensive mechanisms unique among vertebrate divers. Their adaptation to environment lies rather in the perfection of a fundamental facility common to .tial differences in the physiological maall vertebrates. Since there are no essen chinery of air-breathing vertebrates, the adaptative mecha nisms of the divers are actually achieved in an exquisite regulation of respiratory and circulatory functions by nervous and presumably endocrine control systems. Analysis of these control systems is the challenge of future research. REFERENCES
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prolonged diving in the Aznurican alligator. AUigatw missksi~is. Acta Physid. Scud. 53 : 23-45, 1961. 6. ANDERSEN, H. T. Factors detezmining the circulatory adjustments to divizzg. I. Water immezxion. Acta Phyxiol. S&d. 58: 173-185, z963. ANDERSEN, H. T. Factors detezmimzzg the circulatory adjustments to diving. II. Asphyxia. Actu Plrysid. Scod. 58 : zeoo, 1963. 8. ANDERSEN, H. T. The reflex nature of the physiological adjustznurts to diving, and their afferezztpathway. Acta Physid. Scud 58 : 263-273, I g63. 9. ANDERSEN, H. T. In: Thu Eliciiation of Physiological Rcs@nses to Dioing. Oslo: Uzzivezxitetsforlaget, 1963, p. II. IO. ANDERSEN, H. T. Hypezpotasseznla and electrocardi-ographic changea izz the duck during prolonged divizzg. Acta Physiol. Scad. 63 : 292-95, 1965. imposed on diving II. ANDERSEN, H. T. SW vertebrates during prolonged under-water exposure. In: Homcostaris a& Fet&wk Mechanisms. S& No. XVUI. SOG. Ex#l. Bid., edited by G. M. Hughes. London: Cambridge Univ. Press, 1964, pp. 109-127. 12. ANDERSEN, H. T., B. E. HUSTVEDT, MD A. L@V@. Acid-base change2 in diving ducks. Acta Physid. Scud 63 : 128-132, I 965. IS* ANDERSEN, H. T., AND A. L@V@. The effect of carbon dioxide on the respiration of aviazz diver8 (ducks). camp. Biodum. PhysioZ.12 : 451-456, 1964. 14* ARTCM, C. Sur lea rapport2 uztre 1~ zythmc de la reapiz.at&r et le rythme du coer chez lea oiseaux. Arch. Ned. Physiol. IO : 376, 1926. 150 BARCROFI, J. Physiological effecta of insufficiat oxygen supply. Nuture 1o6: x25-129, zgzo-21. 16. BEAU, J. H. S. Recherchea expeziz&ntaleu sur la mort par submezxlon. Arch. Gin. Meci. 2 : 64-76.1860. & la rsJpircrx7* BERT, P. Lqms SWla fi@siologiscOrnpar& t&m. hh : hiffi&C, 1870, pp. 526-553. D. A. Variations in heazt rate during 18. BELKIN, voluntary diving izz the turtle. Psdemys Cvncinnu. Cojka 32X-330, 1964. BOEKE, J. Tastzellen. In: Handbuchtier verglcichendkn A&o&e dtt Wirbeftiem. Berlin: Urban & Schwazzenbag, 1934, vol. II, pp. 861-878. C. Bidrag til Sv+nznefuglerzzea Fysiologl. 20. BOHR, K. Dansb Vi&d. Sdsk. no. 2, 1897. 21. BRADLEY, S. E., ANY R. J. BING. Rezzal function in the harbor seal (Phoca Vitulina L.) during asphyxial ischemia azxl pyzogenic hypereznia. J. C&&u Camp.Physid. zg : 22~37, 1942. 22. BUROW. Ueber das Gef%systezn da Robben. Arch Ad. Physiof. L& (Mudkrs Arch.) 230-258, 1838. 230 CORDAY, E., D. W. IRVING, H. GOLD, H. BERNSTEIN, AND R. B. T. SKELTON. Mwteric vascular insufhciezzcy. Inte&zzal ischezzxiainduced by remote &culatozy disturbances. Am. J. Med. 33: 365-37691962 to apneic 24~ CRAIG, A. B., JR. Heart rate z.eqxzzzses undswater dlvizzg and to breath holding in zzzan.J. A#. PhysioZ.18: 854-862, 1963. P. V. Obrervatiozzs on certain 25. DEHADUI, phyaiologlcal reactions in OpnicspAatur xtria&s exposed to air. Life Sci. I : 653-657, x962. 36. DILL, D, B., AND H. T. EDWARDS. Respiration and metabolism in a young crocodile (Croc&ylw ucutus,cuvicr), capc;rr I-3, 1931. 27* DILL. _ D. B.. AND H. T. EDWARDS. Phyaico.

chemical properties of crocodile blood (Cdylus acutus, Cuviez=). .I. Biol. Chum. go: 515-530, 1931. DILL, D. B., AND H. T. EDWARDS. Pzopertiea of reptilian blood. IV. The alligator (Alligatw missis.@p;cnSis, Daudin). J. CeZZuZur Camp. Physid. 6 : 2430 2549 1935. DILL, D. B., H. T. EDWARDS, A. V. BOCK, AND J. H. TALBOT. Propeztiaz of reptilian blood. III. The chuckwalla (Souromaluru&us, Baird). J. C%l/ulut Com)~ Physiol. 6 : 37-42, 1935. DOOLEY, M. S., ANDT. KOPPANYI. The control of respiration izz the domestic duck (Anus boscus).J. Phannacol.Exptl. Therap. 36: 507-518, 1929. Editorial. Mesentezic vascular izznu&iency. J. Am. Med. Assoc.I 75 : 235, zg6z. EDWARDS, H. T., AND D. B. DILL. Pqertles of reptillazz blood. II. The glla momter (H;rlodcnna susjwtum, Cope). J. C&&w Co@. Physbl. 6 : 2 I -35, x935* ELIASSEN, E. Cardiovascular zesponaeato subme aion asphyxia izz avian divezx dtbak Utiu. Bergs, Mat.-Nat., Siw. no. 2., zg6o. ELSNER, R. W., D. L. FRANKLIN, AND R. L. VAN CIITERS. Cardiac output during diving in 811 uzrrutz-ained sea lion. Nature 202: 809-810, 1964. ELSNER, R. W., AND P. F. SCHOLANDER. Selectivc ischemia izz diving man. Am. &ut J. 65 : 571, 1963. EULER, U. S. VON, G. LILJESTRAND, m Y. ZOTIERMAN. Baroreceptor imp& in the carotid sinus and their zelation to the presmtze refIex. Acta Physid. Scant&2 : z-9, r 941. FEIGL, E., AND B. FOLKOW. Cardiwaacular fc~ sponsu in diving and during brain rtimulation izz ducka. Ada Physid Scan& 57 : 99-z IO, 1963. FLORKIN, M., AND A. C. REDFIELD. On the respiratory function of the blood of the sea lion. Bid. Buil. 61: 422-426, 1931. FRANKLIN, D. L., D. W. BAKER, AE(D R. F. RUSHMER. Pulsed ultrasonic transit time flowmeter. IRE Trans. Biv-Med. Eiednx~ 9: &, 1962. FRANKLIN, D. L., R. L. VAN CII?XRS, AND R. F. RUSHMER. Left ~czmicular function described in physical terms. Citwkion Ru. zI : 7020 711,zg62. GAREY, W. F. Cardiac responsesof f%hesin aaphyxic awirozzzncntrr. Biol. BUZZ.122 : 362-368, 1962. GRATIOLET. RrthGtzbar SUYJonatamir a% lHi$$+ potamt. Paris: Alix, 1867, pp. 350365. GREEN, A. A., AND A. C. REDFIELD. On the respiratory function of the blood of the porpoise. Bid. Bull. 64: M, 1933. GRINNELL, S. W., L. IRVING, AM) P. F. SCHOLANDER. Expez+menta on the relation between blood flow and heart rate in the diving seal. J. csllular Go*. Physiof. 19 : 341-350, 1942. GRODIN, F. S. In: Con&o2 Tluot)( and Biologicu. Systems. New York: Columbia Univ. Preaa, 1963, pp. 143-195. HALDANE, J. S., ANDJ. G. PRIESTLY. The regulation of the lung~ventilation. J. Pliyrid. (London) 32 : 225-266, 2905. HARRISON, R. J., AND J. D. W. TOMLINSON. Nor114 and cxpezimezxtal diving izz the -on seal (Phoca Vitdina). Ext~. Mom. 24 : 386-399, 1960. HIESTAND, W. A., ANDW. C. RANDALL. Species diffmtiation in the -iration of bids f&wing





carbon dioxide administration and the location of inhibitory receptora in the upper respiratory tract. J. Cdldar Comk. Physid. I 7 : 333-340, I 941. 49. HOLLENBERG, N. K., ANDB. UVNAS. The role of the cardiovascular ruponsc in the rt5sistancc to asphyxia of avian divera. Acta PkysioZ. S&watt 58: 150-161, x963. 50. HONG, S. K., H. RAWN, D. H. KANG, S. H. SONG, ANDS. KANG. Diving pattcm, lung volumes, and alveolar gas of the Korean diving woman (Ama). J. A#. Physid. 18: 457-465, 1963. 51. HOWELL, A. B. Aquatic Mammal. Baltimore: Charla C Thomas, 1930. 52. HUXLEY, F. M. On the r&x nature of apnoea in the duck in diving: I. The reflex nature of submersion apnoca., Qau&. J. Exptl. Physid. 6: 147-157, I gI 3. 53. HUXLEY, F. M. On the reflex nature of apnoca in the duck in diving. II. Reflex postural apnoca. Qm#. J. Exptf. PhysioL 6: 159-182, 1913. 5). HUXLEY, F. M. On the r&stance to asphyxia of the duck in diving. f&z& J. Exptf. P&sioL 6: 183gc *g*3* 55. IRVING, L. On the ability of warm-blooded animals to survive without breathing. Sci. Mon. N.Y. 38: 422-48, * 934 56. IRVING, L. The respiration of beaver. J. C&&w cdmp* P&id* 9 : 437-451 P937. 57. IRVING, L. Changa~ in the blood flow through the brain and mqsclcs during the arrcat of breathing. 1938. f&n. J. Physid. 122 : 207-214, $3. IRVING, L. The inacnsitivity of diving animals to Cot. Am. J. Physid. 124: 729134, 1938. 59. IRVING, L. Rapiration in diving mammals Physiof.
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60. IRVING, L. Bradycardia in human divers. J. A#. Physiod.18:489-491,1963. 61. IRVING, L. Comparative anatomy and physiology of gas -port mu%nism8. In: Hu&uok of Physidogy. Skt. III: Resfirh. Wa&qton, D. C.: Am. Physiol. Sot., 1964, vol. 1, pp. ~g&zog. 62. IRVING, L., P. F. SCHOLANDER, AND S. W. GRINNELL. The respiration of the porpo&z Twsiops t~~nCUtaiS. J. Cdhkh C@. P&id. t 7 : 145-I 68, 1$)+X. 63. IRVING, L., P. F. SCHOLANDER, AND S. W. GRINNELL. Significance of the heart rate to the diving ability of seals. J. C&uZar C&& P&id. 18: 283-w. * 90. Q. IRVING, L, P. F. SCHOLAM)ER, AND s. w. GRINNELL. The regulation of arterial blood pres, sure in the atal during diving. Am. J. P@iol. 1%: 557-566s *we 65. IRVING, L., P. F. SCHOLANDER, AND S. W. GRINNELL. Experimental rtudiu of the etioa of sloths. J. CeUuk Camp. P&d. 20: 18g-210, I-. 66. IRVING, L., 0. M. SOLANDT, D. Y. SOLANDT, AND K. C FISHER. Respiratory characteristics of the blood of the aeal. J. a/da Cornp. P&&l. 6: 393-403, 9354 67. IRVING, L., 0. M. SOLANDT, D. Y. SOLANDT, AND K. C. FISHER. The respiratory metabolism of the seal and its adjustment to diving. J. crllutar Camp.Physid. 7 : I 37-151, I 935* 68. IRVING, L., L. J. PEYTON, C. H. BAHN, AND R. S. PETERSON. Action of the heart and breathing during the development of fur seals (Callarhiffur u&us). Phykd. Zool. 36: 1=20,1g63. 6g. JAMES, L. S. Biochemical aspects of asphyxia at

birth. In: A&#&an ti ExtrduCniru fife (Rept. 31st Ross Conf. on Pediat. Rcs.), edited by T. K. Oliver, Jr. Columbus, Ohio : Rolg Laboratories, x959, pp. 66-71. 70.JAMES, L. S. Acidosis of the newborn and its rclation to birth asphyxia. A&Z P&i&. Suppl. 122 : x7-18, x960. 71. JAMES, L. S. Biochemical alterations obrrervcd in the neonate. In: PctinutuZ Phmacdou (Rcpt. 41st Ross Conf. Pcdiat. Rcs.), edited by C. D. May. Columbus, Ohio: Ross Laboratories, 1962, pp. 35-40. 72. JAMES, L. S., I. M. WEISBROT, C. E. PRINCE, D. A. HOLADAY, AND V. APGAR. The acid-base status of human infants in relation to birth asphyxia and the onset of respiration. J. Pcdioi. 52: 3793g4, x958* 73. JOHANSEN, K. Heart activity during cxpcrimmtal diving of snakes. Am. J. PhystX. 197: 604-606, rg5g. 74. JOWSEN, K. Regional distribution of circulating blood during submersion asphyxia in the duck. A&a Physid. &and. 62: r-g, rg6+ 75. JOHANSEN, K., ANDT. AAKHUS. Central cardiovascular responsesto submersion asphyxia in the duck. Am. J. P&id. 205: 1167-1171, 1963. 76. JOHANSEN, K., AND J. KROG. Peripheral citculattory response to submersion asphyxia in the duck. Acta PhysioL Scared. 46 : I gpaoo, 19%. 77. JONES, D. R., AND G. SHELTON. Factors influencing submergence and the heart rate in the frog. J. Exp11.Bid. 41: 417-43. I 964. 78. KANG, B. S., S. H. SONG, C. S. SUH, AM) S. K. HONG. Changes in body temperature and basal metabolic rate of the ama. J. A#. P&rid. 18: 4830 48% Ig63. 79. KOPPmI, T., AND M. S. DOOLEY. The cauac Of cardiac slowing accompanying poetural apnea in the duck. Am. J. PiyJiol. 85 : 311323, I 928. 80. KOPPWI, T., ANDM. S. DOOLEY. Submergence and postural apnea in the mu&rat. Am. J. Physid. 88 : 592-595, 929. 81. KOPPh, T., AND N. KLEITMAN. Body righting and related phenomena in the domestic duck (Anus bows). Am. J. Physiol. 82 : 672-685, 1927. 82. LAJOY, M. H. In : Indurtiol Automatic Contras. Englcwood CIiffs, N. J. : Prentice Hall, Inc., 1959, pp. 82-90. 83. LANDGREN, S. On the excitation mechanism of the carotid barorcccptors. A&a Picyjid. Sccmd. 26: -34s 952. 84. LANGLOIS, P., AM) C. RICHET. Des gaz c&r& par Ia canarda plongcs dana lcau. Co@& &ui. Sac. Bid. 5: 483-486,18g8. 85. LANGLOIS, P., AND C. RICHET. Dosage des gaz dan6 lasphyxie du caxwd. Com$t. Read. Sot. Bid. 5: 7&79s 898. 86. LAURIE, A. H. Some aspects of raqiration in blue and fin whalcu. &covq Rep. 7: 1933. 87. LEIVESTAD, H. The efiect of prolonged subma=sion on the metabolism and the heart rate in the toad. Arbok uti. Bkrge?I, Mat.-Nat., ser. no. 5. I-15, Ig6Ow 88. LEIVESTAD, H., H. ANDERSEN, AND P. F. SCHOLANDER. Phy&logical rsqxxx to air ucpoeurc in the codhh. Science I 26 : 505, 1957. 89. LOMBROSO, U. Uebcr die Rcflexhemmung da Hazeas w&rend dcr Rdbktorischcn Atmuqgshc=mung bci vcrschicdcncn Tieren. 2. Bid. 61: 517-538,



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R. J. S. In: Handbookof Physiologyand Biochcmisrry(42nd ed.). London : J. Murray, 1955, p. 128. H. V., JR., AND J. E. JACKSON. 91. MURDAUGH, Heart rate and blood lactic acid concentration during experimental diving of water snakes. Am. J. Physiol. 202 : I 163-1165, 1962. H. V., JR., B. SCHMIDT-NIEL92. MURDAUGH, SEN, J. W. WOOD, AND W. L. MITCHELL. Cessation of renal function during diving in the trained seal (Phoca vi&&a). J. Celh&zr Co@. Physiol. 58 : 261.266, I g6I. H. V., JR., J. Cl. SEABURY, AND 930 MURDAUGH, W. L. MITCHELL. Electrocardiogram of the diving seal. Circuiatiun Res.g : 358-361, 1961. 940 NOEL PATON, D. The relative infhekce of the labyrinthme and cervical elements in the production of postural apnoti in the duck. Quart. S. Ex#f. Physid. 6: rg7-107, 19x3. 95. NOEL. PATON, D. Submergence and postural apnoea in the swan. Proc. Roy. Sot. Edinbwgh, B 47: 283-w3,Ig27. OLSEN, C. R., D. D. FANESTIL, AND P. F. SCHOLANDER. Some effects of breath holding and apneic underwater diving on the cardiac rhythm in man. J. A#. Physid. I 7 : 461-466, I g62. 970 OLSEN, C. R., D. D. FANESTIL, AND P. F; SCHOLANDER. Some effects of underwater diving on blood gases, lactate and pressure in man. J. AppI. Physid. I 7 : 938-942, I 961. 98* ORR, J. B., AND A. WATSON. Study of the respiratory mechanism -in the duck. J. PhysioZ.(London) 46: 337-348* 1913* P. Changes in blood circulation in 99* POCZOPKO, Rati e.scuZe~a, L., while diving. 2004. Polon, IO: 30-43, 1959+* P. Respiratory exchange in Rana 100. POCZOPKO, csc&n& L., in different respiratory media. ZooZ. Pozon.IO : 46-55, I g5g-60. 01. PROSSER, C. L., AND F. A. BROWN, JR. Comparative Animal Physiology (2nd. ed.). Phibddphia : W. B. Saunders Company, 196x, pp. log-21 I, 388. 102. RAHN, H. (Ed.). Physi&gy of Breath-H& Diving ami tAs Ama of Jean. Washington, D.C.: NatI. Acad. Sci.-NatL Res. Council, 1965, pp. r-367. 103. RANDALL, W. C., D. E. STULKEN, MD w. A. HIESTAND.~Respiration of reptiles as infiuenced by the composition of the inspired air. wu X33-138, x944* 104. REFSUM, H. E. Relationship between state of consciousness and arterial hypoxaemia and- hype+ capnia in patients with pulmonary insufliciency, breathing air. Clin. Sti. 25: 361-367,1963. 105. REFSUM, H. E, Arterial hypoxaemia, serum activities of GO-T, GP-T and LDH, and centrilobular liver cell- necrosis in pulmonary insufficiency. Clin. Sci. 25 : 369-373, I 963. 106. REFSUM, H. E. Severe arterial hypoxemia and liver cell necrosis in patients with pulmonary insufficiency. Acta Med. &and. I 76 : 473-478, 1964. 107. REITE, O., J. KROG, ND K. JOHANSEN. Development of bradycardia during submersion of the duck, Nattwe 200 : 684-685, I 963. 108. RICHET, C. La rhistance des canards %l%sphyxie. Compt. Rend. Svc. Bid. I : 244-245, 1894. C. Iniiuence de latropine sur la durde de 109. RICHET, lasphyxie chex le canard. Compt. Rend. SOL Biol. I : 789-790s 1894.

RICHET, C. De linfluence de leducation sur la resistance du canard B lasphyxie. COT@% Rend. SOG. Biof. 5: 481-483, 1898. III. RICHET, C. De la r&istance des canards B lasphyxie. Compt. find. Sot. Biof. 5 : 685-686, r8g8. 112. RICHET, C. De la r&stance des canards a lasphyxie. J. Physiol. Pathoi. Gdn. I : 641-650, 1899. 113. ROBIN, E. D., H. V. MURDAUGH, JR., W. PYRON, E. WEISS, AND P. SOTERES. Adaptations to diving in the harbor seal-gas exchange and ventilatory response to CO%. Am. J. Physiol. 205; 1175-1177, I$% 114. ROBINSON, D. The muscle hemoglobin of seals as an oxygen store in diving. S&nce go: 276-277, 1939. 115. SALT, G. W., ANI) E. ZEUTHEN. The respiratory system. In: Biology and cbmfiarativePhysiologyof Birds, edited by A. J. Marshall. New York: Academic Press, 1960, vol. I. 116. SAPIRSTEIN, L. A. Regional blood flow by fractional distribution of indicators. Am. J. Physiol. $93: 161-168, 1958. 117. SCHOLANDER, P. F. Experimental investigations on the respiratory function in diving mammals and birds. HvaZr&fets Sktifftct; Norske VidenskapS-Akud., Oslo 22: I-131,1940. 118. SCHOLANDER, P. F. Physiological adaptations to diving in animals and man. Harvy Lect. 57: 93-I IO, rg6r-62. 119. SCHOLANDER, P. F. The masterswitch of life. Sci. Am. 2og: g2--Io6,Ig63. 120. SCHOLANDER, P. F. Animals in aquatic environ. ments: diving mammals and birds. In,: Handbook of Physi>logy. sect. 4: Adaptation to the Enviionment. Washington, D. C. : Am. Physiol. Sot., 1964, pp. 729-739* 121. SCHOLANDER, P. F., E. BRADSTREET, AND W. F. GAREY. Lactic acid response in the grunion. 1962. Camp. B&&m. Physioi. 6: 201-203, 122 SCHOLANDER, P. F., H. T. HAMMEL, D. H LEMESSURIER, E. HEMMINGSEN, AND w. GAREY. Circulation adjustment in pearl divers. J. A##. Physiol. I 7 : 184-1 go, 1962. 123. SCHOLANDER, P. F., AND L. IRVING. Experimental investigations on the respiration and diving of the Florida manatee. J. CeliadarCome. PhysiX 17: x6g-rgx, 1g41. I 24. SCHOLANDER, P. F., L. IRVING, AND S. w. GRINNELL. Aerobic and anaerobic changes in the seal muscles during diving. J. Bid. Chem. 142: 431 440, 1942. 125. SCHOLANDER, P. F., L. IRVING, AND S. W. GRINNELL. On the temperature and metabolism of the seal during diving. J. Ceflulur Co;nP. Physiol. 19: 67-78,1g42. 126. SHELTON, G,, AND D. R. JONES. Central-. blood pressure and heart output in surfaced andsubmerged frogs. J. Etcptl. Biol. 42 : 33g-357, 1965. 127. SHELTON, G., AND D. J. RANDALL. The relationship between heart beat and respiration in teleost fish. Camp. B&hem. Physiol. 7: 237-250, rg62. 128. SONG, S. H., D. H. KANG, B. S. KANG, AND S. K. HONG. Lung volumes and ventilatory responses @J high COs and low 0s in the ama. J. && Physiol. 28: 466-470, 1963. G. Die, Ama und ihre Arbeit. Afbe*urng. TERUOKA, physior. 5: 239, 1932. H. Kristallinisches Myoglobin. I. 130. THEORELL,

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Mitteilung : Kristallisiercn und Rciningung dcs Myoglobins sowie VorliuQe Mitteilung ucba scin Molekulargcwicht. Bioc~. 2.252: 17, 1932. 131. THEORELL, H. Kristalhnixhcs Myoglobin. V. Mittcihmg : Die Sauerstoffbindungskurve dea Myoglobins. &&em. 2. 268 : 73-82, 1934. 132. VINCENT, S., AND T. CAMERON. A note on an inhibitory respiratory reflex in the frog and some other animals. J. Camp. iVeurot. 31: 28pg2, rgao. 133. WASTL, H., AND G. LEINER. Bcobachtungcn ueba die Blutgase ti Vagcln. I-II-III. Arch. Ga Physid. 227: 367.474# 1931. rg4. WEISBROT, I, W., L. S. JAMES, C. E. PRINCE, D. A. HOLADAY, AND V. APGAR. Acid-base homatasia of thenewborn infant during the firat 24 houra of life, J. Pediat. 52 : 3g5+3, 1958.

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