Cariporide (HOE-642) improves cardiac allograft preservation in a porcine model of orthotopic heart transplantation.
BACKGROUND
Acute graft dysfunction caused by ischemia-reperfusion injury is recognized as a major source of morbidity and mortality following adult heart transplantation. The aim of this study was to determine whether treating the donor and recipient with cariporide, an inhibitor of the sodium-hydrogen exchanger, could reduce ischemia-reperfusion injury.


METHODS
A porcine model of donor brain death, hypothermic ischemic preservation, and orthotopic cardiac transplantation was used. Allografts in both the control group (CON, n=6) and treatment group (CAR, n=6) were arrested and stored for 4 hours in the extracellular crystalloid cardioplegia currently used in the clinical transplantation program at our institution. In addition, both the donor and recipient animals in the CAR group received a single intravenous dose of cariporide (2 mg/kg) 15 minutes before harvesting and reperfusion, respectively.


RESULTS
The initial rate of troponin I release was significantly lower in recipients of CAR hearts than in recipients of CON hearts (P =0.020). All hearts were weaned successfully from bypass. More CAR hearts were weaned successfully at the first attempt, at 1 hour post-reperfusion, than CON hearts (6 of 6 vs 3 of 6), but this did not achieve statistical significance. Left ventricular contractility (preload recruitable stroke-work relationship) and left ventricular compliance (end-diastolic pressure-volume relationship) were significantly better preserved in CAR hearts than CON hearts (both P <0.0001).


CONCLUSIONS
Myocardial injury was reduced, and contractile function was better preserved in allografts that received cariporide, compared with allografts that received conventional preservation alone.
Ryan
Jonathon B
JB
Department of Heart and Lung Transplantation, St. Vincent's Hospital, Darlinghurst, Australia.
Hicks
Mark
M
Cropper
Jonathan R
JR
Garlick
Sarah R
SR
Kesteven
Scott H
SH
Wilson
Michael K
MK
Feneley
Michael P
MP
Macdonald
Peter S
PS
D000818:Animals; D001794:Blood Pressure; D001810:Blood Volume; D035061:Control Groups; D015925:Cryopreservation; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D016027:Heart Transplantation; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D013318:Stroke Volume; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D014184:Transplantation, Homologous; D019210:Troponin I / Q000097:blood; D016277:Ventricular Function, Left
D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D019210:Troponin I; C093373:cariporide