Sepsis: Going to the Heart of the Matter

Abstract

Although myocardial depression is the predominant cause of death in severe sepsis/septic shock, it remains disputed whether the functional changes are a consequence of structural alterations. If we look at myocardial dysfunction from the perspective of a critically ill patient, there are a few questions to be asked: What causes myocardial dysfunction? What is the pathophysiology of cardiac dysfunction and death? Is there something that could be done to prevent the outcome? Each of these questions is interrelated and the answers will be more easily addressed if we continue to understand the basic mechanisms that are implicated. The principal mechanisms proposed for the pathogenesis of myocardial dysfunction support a prominent role for functional rather than anatomical abnormalities. However, attempts to reduce the high mortality in septic patients by manipulating the functional alterations have provided limited success. In recent years, the concept of septic cardiomyopathy has evolved, which implies alterations in the myocardial phenotype. This review includes an overview on the activation of the immune system and therapeutic approaches in sepsis, myocardial structural changes in the human septic heart, experimental models of sepsis, and cellular, molecular and functional myocardial changes seen in a variety of experimental sepsis models. The abnormal parameters discussed may emerge as therapeutic targets, for which modulation might provide beneficial effects on cardiovascular outcome and mortality in sepsis in the future.

Pathophysiology of the Cardiorenal Syndromes: Executive Summary from the Eleventh Consensus Conference of the Acute Dialysis Quality Initiative (ADQI)

“…Toxicity from markedly elevated neurohormones, particularly catecholamines, has been suggested in cases of overwhelming injury to the heart and kidneys, particularly in those with susceptible adrenergic receptor polymorphisms [66,67]. When sepsis is complicated by shock, it is possible that ischemia/reperfusion injury occurs in both organs resulting in even further endothelial injury and impairment of microcirculatory perfusion [68,69]. At the cellular and tissue level, abnormal cell signaling, cell cycle arrest, loss of control over oxidative reactions due to the liberation of catalytic iron from structural proteins (myoglobin) and mitochondria, acute cell death, apoptosis, and tissue necrosis can all be in the final common pathway in CRS type 5 [70].…”

Post-mortem diagnostics in cases of sepsis. Part 2. Biochemical and morphological examinations

“…Myocardial failure is the main cause of death in the course of severe sepsis and septic shock. Studies conducted to date demonstrate that cardiac damage is mainly related to functional changes [15]. Although significant apoptotic lesions in muscle fibres have been shown in the animal model, clinical practice demonstrates that identified cardiac function disorders are not consistent with lesions of this type [13,16,17].…”

“…Niewydolność mięśnia sercowego jest główną przyczyną śmierci w przebiegu ciężkiej sepsy i wstrząsu septycznego. Przeprowadzone dotychczas badania wskazują, że uszkodzenie serca wiąże się głównie ze zmianami czynnościowymi [15]. Mimo że stwierdzono na modelu zwierzęcym istotne zmiany apoptyczne włókien mięśniowych, praktyka kliniczna pokazuje, że występujące zaburzenia funkcji serca nie są adekwatne do tego typu zmian [13,16,17].…”

Septic cardiomyopathy : pathophysiology and prognosis

“…(6) Myocardial depressant factor includes a variety of molecules all with depressant effects on the myocardium not only bacterial derived toxins such as endotoxin / lipopolysaccharide but also TNF-α and IL-1ß. (7,8) Sepsis leads to the expression of inducible NO synthase (iNOS) in the myocardium which results in high levels of nitric oxide locally. This disrupts intracellular calcium metabolism, reducing cytosolic calcium levels and impairing contractility.…”