Dexrazoxane prevents myocardial ischemia/reperfusion-induced oxidative stress in the rat heart.
BACKGROUND
Dexrazoxane (Dex), used clinically to protect against anthracycline-induced cardiotoxicity, possesses iron-chelating properties. The present study was designed to examine whether Dex could inhibit the ischemia/reperfusion (I/R) induced damage to the rat heart.


METHODS
Isolated perfused rat hearts were exposed to global ischemia (37 degrees C) and 60 min reperfusion. Dex was perfused for 10 min prior to the ischemia, or administered intraperitoneally (150 mg) 30 min prior to anesthesia of the rats. I/R caused a significant hemodynamic function decline in control hearts during the reperfusion (e.g., the work index LVDP X HR declined to 42.7+/-10%). Dex (200 microM) applied during the preischemia significantly increased the hemodynamic recovery following reperfusion (LVDP X HR recovered to 55.7+/-8.8%, p<0.05 vs. control). Intraperitoneal Dex, too, significantly increased the hemodynamic recovery of the reperfused hearts. I/R caused an increase in oxidation of cytosolic proteins, while Dex decreased this oxidation.


CONCLUSIONS
The decrease in proteins carbonylation and correlative hemodynamic improvement suggests that Dex decreases I/R free radical formation and reperfusion injury.
Ramu
Eyal
E
The Joseph Lunenfeld Cardiac Surgery Research Center, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem, Israel.
Korach
Amit
A
Houminer
Esther
E
Schneider
Aviva
A
Elami
Amir
A
Schwalb
Herzl
H
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011929:Razoxane / Q000494:pharmacology*
D002316:Cardiotonic Agents; D002614:Chelating Agents; D011929:Razoxane