Use of the cardioprotectants thymosin ?4 and dexrazoxane during congenital heart surgery: proposal for a randomized, double-blind, clinical trial
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 that result in cardiac injury and dysfunction. Thymosin ?4 (T?4) is a naturally occurring peptide that has cardioprotective and antiapoptotic effects. Similarly, dexrazoxane provides cardioprotection by reduction of toxic reactive oxygen species (ROS) and suppression of apoptosis. We propose a pilot pharmacokinetic/safety trial of T?4 and dexrazoxane in children less than one year of age, followed by a randomized, double-blind, clinical trial of T?4 or dexrazoxane versus placebo during congenital heart surgery. We 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 clinical utility of T?4 and/or dexrazoxane in ameliorating ischemia-reperfusion injury during congenital heart surgery.
thymosin ?4 dexrazoxane congenital heart surgery cardiopulmonary bypass