Use of the cardioprotectants thymosin β4 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 β4 (Tβ4) 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 Tβ4 and dexrazoxane in children less than one year of age, followed by a randomized, double-blind, clinical trial of Tβ4 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 Tβ4 and/or dexrazoxane in ameliorating ischemia-reperfusion injury during congenital heart surgery.
Congenital Heart Surgery Unit, Medical City Children's Hospital, Dallas, Texas 75230, USA. dstrom115@yahoo.com
Daniel
D
Stromberg
Tia
T
Raymond
David
D
Samuel
David
D
Crockford
William
W
Stigall
Steven
S
Leonard
Eric
E
Mendeloff
Andrew
A
Gormley
D017209:Apoptosis / Q000187:drug effects; D006348:Cardiac Surgical Procedures / Q000379:methods*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D011929:Razoxane / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013947:Thymosin / Q000627:therapeutic use*; D000099201:Thymosin beta(4)
D011929:Razoxane; D017382:Reactive Oxygen Species; D013947:Thymosin; D000099201:Thymosin beta(4)