When does the heart fail during shock?

Abstract

Early reports have attributed cardiac failure during acute and chronic models of shock to peripheral vascular dysfunction and decreased venous return. More recently interest has focused on the heart as a primary target responsible for cardiovascular changes associated with acute endotoxin or hemorrhagic shock. At present, it remains controversial whether the heart fails early following the induction of experimental hypodynamic shock. Data from our laboratory have shown that myocardial contractility was increased early following acute endotoxin and splanchnic artery occlusion shock, and it was not until the agonal or terminal phase that contractility was depressed. We have used the slope of the left ventricular pressure-dimension relationship (Ees) as our index of contractile function. This technique is preferential since it is not affected by changes in the loading conditions on the heart. Unlike most reports that have used LV dP/dt as an index of contractility in the intact animal, we have shown that Ees and LV dP/dt do not uniformly reflect changes in contractility. LV dP/dt and related measures do, however, reflect the overall global changes in myocardial performance, which are affected by changes in preload, afterload, heart rate, and contractility. The reductions in LV dP/dt therefore mainly reflect the changes in arterial blood pressure associated with acute hypodynamic shock. The increase in contractility reported during endotoxin shock were shown to be induced by stimulation of beta-adrenergic receptors--when the beta-blocking drug, propranolol, was given to animals during shock, contractility decreased. The mechanism(s) responsible for the failure of the heart during the late or agonal periods of shock is (are) unknown. We have shown in dogs who die as a result of endotoxin shock that the hearts exhibit a progressive energy deficit, whereas animals surviving the experimental protocol maintained levels of ATP and creatine phosphate. It is unclear if the changes in high-energy phosphates during endotoxin shock cause irreversibility. Other potential mediators of cardiac failure have included ischemia/hypoxia, toxic myocardial depressant factors, deterioration of sympathetic influences on the heart, electrophysiologic and ionic disturbances, etc. The relationship between these factors and failure of the heart in vivo during various shock paradigms remains to be elucidated.