Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery: Proposal for Pilot Investigation

Neonates and infants undergoing heart surgery with cardioplegic arrest experience both inflammation and myocardial ischemia-reperfusion \[IR\] injury. These processes provoke myocardial apoptosis and oxygen free radical formation which result in cardiac injury and dysfunction. Dexrazoxane is a derivative of EDTA that is approved for prevention of anthracycline-related cardiotoxicity. It provides cardioprotection through reduction of toxic reactive oxygen species \[ROS\], and suppression of apoptosis. The deleterious effects of cardiopulmonary bypass \[CPB\] with cardioplegic arrest of the heart during congenital heart operations greatly influence postoperative morbidity and mortality. Neonates and infants undergoing cardiac surgery experience both a systemic inflammatory response, and myocardial IR injury as cardioplegic arrest is reversed. These processes provoke elaboration of cytokines and activation of the complement cascade, as well as oxygen free radical formation and induction of myocardial apoptosis (1, 2, 3). Frequently, myocardial injury and cardiac dysfunction ensue, leading to low cardiac output syndrome and multi-system organ failure. The irreversible component of these injuries, in addition to the abnormal workloads imposed on the myocardium from the anatomic defects themselves, may have consequences for long-term cardiac function, and may in part explain contractile dysfunction observed late after congenital heart The investigators propose a pilot pharmacokinetic/safety trial of dexrazoxane in children 0-6 months of age, followed by a randomized, double-blind, clinical trial of dexrazoxane vs placebo during congenital heart surgery. The investigators will evaluate postoperative time to resolution of organ failure, development of low cardiac output syndrome, length of cardiac ICU and hospital stays, and echocardiographic indices of cardiac dysfunction. Results could establish the safety and clinical utility of dexrazoxane in ameliorating ischemia-reperfusion injury during congenital heart surgery.