Sodium-hydrogen exchanger inhibition, pharmacologic ischemic preconditioning, or both for extended cardiac allograft preservation.
BACKGROUND
The aim of this study was to determine the efficacy of cariporide (a sodium-hydrogen exchanger inhibitor), BMS180448 (a pharmacologic ischemic preconditioning agent), and the combination thereof, as adjuvant therapies for extended cardiac allograft preservation.


METHODS
A porcine model of donor brain death and orthotopic heart transplantation was used. All hearts were arrested and stored for 14 hr in an extracellular preservation solution. Control hearts (CON; n=3) did not receive any additional treatment. Treated hearts received BMS180448 alone (BMS; n=3), cariporide alone (CAR; n=6), or both BMS180448 and cariporide (B+C; n=6). Donors of BMS180448-treated hearts received 2 mg/kg, 15 min before explantation. Donors and recipients of cariporide-treated hearts received 2 mg/kg, 15 min before explantation and reperfusion, respectively.


RESULTS
The CON and BMS arms of the study were terminated after three transplantations because initial results in these groups were poor. Significantly, none of the control hearts could be weaned successfully from bypass, whereas all of the treated hearts were weaned successfully (CAR vs. CON and B+C vs. CON: P=0.012). The rate of troponin I release during the first 3 hr after reperfusion was significantly lower in CAR (P=0.0180) and B+C (P=0.0154) recipients than in CON recipients. Mean plasma troponin I levels (microg/mL) 3 hr after reperfusion were as follows: CON 633+/-177, BMS 576+/-110, CAR 346+/-93, and B+C 296+/-97.


CONCLUSIONS
In this porcine model of extended cardiac allograft preservation, cariporide was more effective than BMS180448 as an adjuvant to our usual preservation solution. There was no additional benefit from the combination of the two therapies.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006146:Guanidines / Q000494:pharmacology*; D016027:Heart Transplantation; D019194:Ischemic Preconditioning / Q000379:methods*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D014184:Transplantation, Homologous; D019210:Troponin I / Q000097:blood
D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D002316:Cardiotonic Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D019210:Troponin I; C093373:cariporide; C084684:BMS 180448