Does the heart fail in endotoxin shock?

Evidence for a major participatory role of the myocardium in the hemodynamic response to endotoxemia and sepsis has been controversial. Early interpretations about in situ changes in cardiac performance during shock were confounded by the concomitant influence of uncontrolled pathophysiologic adjustments in cardioactive variables such as preload, afterload, sympathoadrenal discharge, left ventricular diastolic compliance (stiffness), and in some studies myocardial hypoperfusion/ischemia. Despite such complexities, many recent studies with intact subjects and isolated preparations consistently point toward a relatively early involvement of myocardial dysfunction in circulatory shock syndromes associated with gram-negative bacteria and sepsis. The cardiac dysfunction cannot be accounted for by a direct toxic effect of the endotoxin molecule itself on cardiac myocytes. Rather, evidence is compelling that endotoxin interacts first with other types of cellular or tissue elements. The latter evoke biologic reactions through some unknown pathway culminating in deleterious effects in the heart. Discovery of the casual mechanism(s) responsible for myocardial sequelae of endotoxemia and sepsis remains a key objective in experimental and clinical research in circulatory shock pathogenesis.