TY - JOUR
T1 - Use of the cardioprotectants thymosin β4 and dexrazoxane during congenital heart surgery
T2 - Proposal for a randomized, double-blind, clinical trial
AU - Stromberg, Daniel
AU - Raymond, Tia
AU - Samuel, David
AU - Crockford, David
AU - Stigall, William
AU - Leonard, Steven
AU - Mendeloff, Eric
AU - Gormley, Andrew
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Cardiopulmonary bypass
KW - Congenital heart surgery
KW - Dexrazoxane
KW - Thymosin β4
UR - http://www.scopus.com/inward/record.url?scp=84867386677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867386677&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.2012.06710.x
DO - 10.1111/j.1749-6632.2012.06710.x
M3 - Article
C2 - 23050818
AN - SCOPUS:84867386677
SN - 0077-8923
VL - 1270
SP - 59
EP - 65
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
IS - 1
ER -