Presentasi Gangguan Jantung

Pada Sepsis
Wira Winardi
 The New Definition of Sepsis
Sepsis has been defined by consensus as a
systemic inflammatory response syndrome (SIRS)
to infection
Annane D, Bellissant E, Cavaillon JM. Septic
shock. Lancet. 2005;365:6378

Ganoderma lucidum
life-threatening organ dysfunction caused
by a dysregulated host response to infection

2016 Third International Consensus

2 Definitions for
Sepsis and Septic Shock (Sepsis-3)
European Society of Intensive Care Medicine
(ESICM) and Society of Critical Care Medicine 2
(SCCM) 2017
 Schematic Diagram of New Sepsis
Definition Comparison to Prior Definitions

Rhee C, Klompas M. New Sepsis and Septic Shock Definitions Clinical Implications
and Controversies. Infect Dis Clin N Am.2017
Sepsis Patophysiology
Features of Sepsis-Related Cardiac
Dysfunction

Impaired contractility

Diastolic dysfunction

Reduced cardiac index and

ejection fraction
 Sepsis-Related Cardiac Dysfunction:

Inflammation Energy Mismanagement

complement activation, reduction of cardiac fatty acid
Coagulation oxidation

macrophagic mitochondrial dysfunction.

endothelial
thrombocytic
cellular immunity)

Cardiac -Adrenergic Signaling impairment

PAMPs Induced cytokines production

Wibke Schulte, Jrgen Bernhagen, and Richard Bucala, Cytokines in Sepsis: Potent
Immunoregulators and Potential Therapeutic TargetsAn Updated View, Mediators of
Inflammation, vol. 2013, Article ID 165974, 16 pages, 2013. doi:10.1155/2013/165974
Li Y, et all. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis Burns & Trauma
December 2013 Vol 1 Issue 3
Potential mechanisms and mediators by which cytokines may contribute to cardiac myocyte
contractile dysfunction.

Ralph A. Kelly, and Thomas W. Smith Circulation.

1997;95:778-781
 Secretion of Proinflamatory Citokine:
TNF
Genetic ablation of TNF receptor 1 (TNFr1/)
prolonged survival in mice that underwent
polymicrobial sepsis with CLP
Treatment of BALB/C mice with anti-TNF
antibodies prior to administration of LPS
improved survival rate
Ebach DR, Riehl TE, Stenson WF. Opposing effects of tumor necrosis factor receptor 1 and 2 in sepsis due to cecal
ligation and puncture. Shock. 2005; 23:3118. [PubMed: 15803053]

Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice
from lethal effect of endotoxin. Science. 1985; 229:86971. [PubMed: 3895437]

ISSUE: a large number of clinical trials investigating anti-inflammatory agents failed to

treat sepsis
Secretion of Proinflamatory Citokine:
TNF
Enhances production of macrophages from
progenitor cells

Promotes the activation and differentiation of

macrophages

Prolongs the survival of macrophage

TNF Enhances the expression of adhesion molecules,

such as intercellular adhesion molecule (ICAM)-1
and vascular cell adhesion molecule (VCAM)-1, and
chemokines

Increases integrin adhesiveness in neutrophils and

promotes their extravasation into tissues

Activating macrophages to secrete other

proinflammatory cytokines (IL-6, IL-8, and MIF),
lipid mediators, and reactive oxygen and nitrogen
species
Secretion of Proinflamatory Citokine:
IL-1

produced by macrophages, monocytes, and

neutrophils in response to TNF
Ignites iNOS production, suppresses cardiac
contractility
IL-1
IL-1 signaling , mortality of sepsis

Inhibition of IL-1 with improved response in

sepsis.
Hedayat M, Mahmoudi MJ, R.Rose N, Rezaei N. Proinflammatory cytokines in heart failure :
double-edged swords. Heart Failure Rev. 2010;15:543-62.
 TNF
IL 1

Spingosine

Alterations in Ca2+ homeostasis

Endothelial activation in Sepsis
Inflammation As a Driving Force of
Septic Cardiac Dysfunction
Terima Kasih
Complications of Cardiac -Adrenergic
Signaling in Sepsis
excessive stimulation of cardiac ARs and
particularly of the pro-apoptotic 1AR cause
myocardial damage due to intracellular
calcium overload and induction of cell death