IJCS | Volume 31, Nº6, November / December 2018

645 Jorge et al. Myocardial dysfunction and mortality in sepsis Int J Cardiovasc Sci. 2018;31(6)643-651 Review Article Joseph et al. 17 demonstrated that the activation of the NADPH oxidase 2 – an enzyme complex found in the plasma membrane and involved in the maintenance of immune function, cell growth, and apoptosis – is one of the responsible factors for the oxidative stress induced by sepsis, and that its inhibition decreases not only the production of oxygen-derived reactive species, but also preserves the mitochondrial function and homeostasis of intracellular calcium, relieving the systolic dysfunction induced by sepsis in vivo. 17 - Necrosis and apoptosis of cardiomyocytes: focal myocardial necrosis and subendocardial necrosis have been identified in experimental models of sepsis, while necrosis of the contractile bands was identified by Schmittinger et al. 18 in a prospective study involving the histological analysis of 20 biopsied human hearts. - Myocardial infiltration: myocardial infiltration by neutrophils, monocytes, and macrophages is the main histological finding in septic cardiomyopathy. This inflammatory process is associatedwith interstitial edema, fibrosis, and formationof thrombi in themicrocirculation. 18,19 Left ventricular systolic dysfunction and mortality LV systolic dysfunction has been the most studied and reported dysfunction in the literature, and despite Figure 2 - Molecular factors involved in myocardial depression. Adapted from Antonucci E, Fiaccadori E, Donadello K, Taccone FS, Franchi F, Scolletta S. Myocardial depression in sepsis: From pathogenesis to clinical manifestations and treatment. Vol. 29, Journal of Critical Care. 2014. p. 500-11. Nitric oxide Oxygen water L-arginine L-citrulline Extracellular Intracellular Calcium channels Glutathione depletion Reduced dihydropyridine receptors Depressive effect Endothelin-1 Immune response inflammation Apoptosis or necrosis Depressive effect Toll-like receptor Cytokines Mitochondrial dysfunction