Pyruvate: A physiologic energy substrate and antioxidant for cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is necessary for many complex cardiac surgeries including valve replacement, correction of congenital cardiac anomalies and difficult coronary artery revascularizations. Contact of blood with foreign surfaces within the extracorporeal circuit, hypothermia, microemboli, ischemia, and surgical trauma elicit a massive systemic inflammatory response. If unchecked, this inflammation inflicts endorgan damage culminating in significant postoperative morbidity and mortality. Reactive oxygen and nitrogen metabolites are generated upon reperfusion and released by activated neutrophils, initiating the inflammatory cascade. Cardioplegic arrest and reperfusion impose significant oxidative stress on cardiac tissue, which inactivates myocardial enzymes and produces cardiac edema. Pyruvate, a naturally occuring metabolic intermediate, energy substrate and powerful antioxidant, blunts intestinal and hepatic inflammation during endotoxic and septic shock. The antioxidant actions of pyruvate are proposed to interrupt systemic and intramyocardial inflammatory cascades, ameliorate injury to the myocardium and, thus, enhance post-surgical recovery of cardiac mechanical function as well as stabilize atrial rhythm. This proposed mechanism has been tested in swine subjected to cardioplegic arrest on CPB. Relative to control cardioplegia, pyruvate-fortified cardioplegia prevented oxidative stress and edema, bolstered endogenous antioxidant defenses, protected oxidant-sensitive enzymes and increased the myocardial energy state. Results of these investigations, as well as encouraging results from human studies, provide crucial empirical support for the use of pyruvate in cardioplegia to mitigate post-surgical inflammation and cardiac dysfunction.