IJCS | Volume 31, Nº6, November / December 2018

644 Jorge et al. Myocardial dysfunction and mortality in sepsis Int J Cardiovasc Sci. 2018;31(6)643-651 Review Article reduced glutathione, oxidative stress, and mitochondrial dysfunction. 8,9 Although its exact role in the pathogenesis of myocardial dysfunction in sepsis is unknown, endothelin-1 has been demonstrated in animal models to directly affect the myocardial performance as well. 10 - Alterations of calcium channels: the involvement of these channels with myocardial dysfunction can be explained by the relationship between intracellular calcium concentrations and cardiac contractility, but experimental models have shown that despite the reduction in L-type calcium channels observed in sepsis leading to a reduction in cardiac repolarization, there is no clear association between the resulting shortening of the duration of action potential and a possible reduction in myocardial contractility. 11 - Toll-like receptors: toll-like receptors (TLRs) recognize specific pathogenic molecular patterns and play an important role in innate immunity. Experimental models have demonstrated that the activation of nuclear factor κ B mediated by TLR4 plays an important role in the development of myocardial depression 12 and that TLR3 knockout mice maintain a normal cardiac function even during sepsis. 13 - Adrenergic hyperstimulation: in the early stage of sepsis, there is a massive release of catecholamines from the autonomous nervous system, intestine, leukocytes, and macrophages, resulting in hyperstimulation of alpha and beta-adrenergic receptors, which finally leads to their downregulation and resistance to circulating catecholamines. 14,15 - Mitochondrial dysfunction: an adequate supply of adenosine triphosphate (ATP) is fundamental to the maintenance of myocardial contractility, and several mechanisms of mitochondrial lesion can play an important role in the development of myocardial dysfunction during sepsis, such as edema of the mitochondrial matrix, oxidative stress, alteration of membrane permeability, imbalance between biogenesis processes (growth and division), and mitophagy (removal of dysfunctional mitochondria by autophagy). 16 Figure 1 - Main mechanisms of cardiac dysfunction, along with its consequences and impact. Adapted from Vieillard-Baron A, Cecconi M. Understanding cardiac failure in sepsis. Intensive Care Med 2014;40:1561. Depressed intrinsic myocardial performance (100%) - May induce cardiac dysfunction very early - May be unmasked according to preload and afterload conditions - May lead to cardiac failure - Is reversible LV diastolic dysfunction (50%) - LV compliance impairment with slight LV dilatation - LV relaxation impairment - May modify the tolerance to fluids LV systolic dysfunction (up to 60%) - Is afterload sensitive - Does not increase LV filling pressure - Is usually corrected by small dose of dobutamine RV systolic dysfunction (30-50%) - Can be isolated or associated with acute lung injury or acute respiratory distress syndrome - Is dependent on respiratory settings - Decreases venous return