Fig. 1

Mechanisms of sepsis-induced cardiomyopathy. Endotoxins cause depressed cardiac contractility, which is mediated by enhanced nitric oxide (NO) production. Tumor necrosis factor and interleukin-1β also contribute to NO overproduction. NO is believed to act in the heart by decreasing myofibril response to calcium, inducing mitochondrial dysfunction, and downregulating β-adrenergic receptors. These reactions lead to sepsis-induced cardiomyopathy. Methylene blue, an inhibitor of the NO pathway, counteracts the myocardial depression. Histones occur inside the nucleus and can be released into circulation because of extensive inflammation and cellular death during sepsis. Since cardiac dysfunction can be ameliorated by anti-histone antibodies in a septic mouse model, histones may be implicated in the pathophysiology of sepsis-induced cardiomyopathy