Na+/H+ exchange inhibition and antioxidants lack additive protective effects after reperfusion injury in the working heterotopic rat heart isograft.
BACKGROUND
The utility of combining strategies of myocardial protection was studied in intact rat hearts subjected to 1 hour of ischemia and 40 minutes blood reperfusion.


METHODS
Lewis rats (n = 48) were divided into 4 transplant groups. Twenty-four hearts were arrested by coronary perfusion with hypothermic Celsior solution at 60 mm Hg. The aortic valve was punctured to introduce volume into the left ventricle (LV), and the hearts were abdominally isografted. Animals were either given both the antioxidant probucol (300 mg/kg) and the sodium-hydrogen exchange inhibitor cariporide (5 mg/kg) (CP; n = 6), just cariporide (CAR; n = 6), just probucol (PROB; n = 6), or neither drug (CON; n = 6). After 40 minutes of blood reperfusion, transplanted hearts were rearrested. The control recipients' native hearts (native; n = 6) were also arrested. Postmortem LV compliance relations and myocardial water content (MWC) were measured.


RESULTS
Grafts protected by probucol were significantly more compliant than controls and significantly less compliant than grafts protected by cariporide alone and with both cariporide and probucol (p = 0.0001, analysis of variance). Compliance relations for CP overlapped those for CAR. All grafts were less compliant than natives. MWC was significantly greater in controls and PROB than in natives.


CONCLUSIONS
Pretreatment with cariporide in the setting of ischemia-reperfusion injury provides greater protection against the development of diastolic abnormalities than probucol when Celsior solution is used for both arrest and preservation. In this model, there is no advantage to combining the drugs, supporting the hypothesis that there is an overlapping mechanism of protection.
Rabkin
David G
DG
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Curtis
Lauren J
LJ
Weinberg
Alan D
AD
Spotnitz
Henry M
HM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002306:Cardiac Volume / Q000187:drug effects; D003187:Compliance / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006146:Guanidines / Q000494:pharmacology*; D016027:Heart Transplantation / Q000502:physiology*; D009929:Organ Size; D011341:Probucol / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology*; D016042:Transplantation, Heterotopic / Q000502:physiology; D014185:Transplantation, Isogeneic / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D011341:Probucol