Molecular events in the cardiomyopathy of sepsis

Abstract

Septic cardiomyopathy is a well-described complication of severe sepsis and septic shock. However, the interplay of its underlying mechanisms remains enigmatic. Consequently, we constantly add to our pathophysiological understanding of septic cardiomyopathy. Various cardiosuppressive mediators have been discovered, as have multiple molecular mechanisms (alterations of myocardial calcium homeostasis, mitochondrial dysfunction, and myocardial apoptosis) that may be involved in myocardial dysfunction during sepsis. Finally, the detrimental roles of nitric oxide and peroxynitrite have been unraveled. Here, we describe our present understanding of systemic, supracellular, and cellular molecular mechanisms involved in sepsis-induced myocardial suppression.

Figure 1

Flowchart of the presumed intracellular signaling in cardiomyocytes leading to myocardial production of cardiodepressant mediators.

Figure 2

Myocardial contractile dysfunction sepsis might, in part, be triggered by C5a. Question marks illustrate open, to date unanswered, questions.

Figure 3

Physiologic regulation of calcium flux in cardiomyocytes.

Figure 4

A depiction of supracellular, systemic, and molecular events involved in the cardiomyopathy of sepsis. See text for details.