Pretreatment of the Donor with AICAR Significantly Protects Rat Heart Graft from Prolonged Cold Ischemia/Reperfusion Injury in an Isolated Model.

Abstract

Purpose: To investigate whether pretreat donor rat with AMP-activated protein kinase (AMPK) activator AICAR can reduce heart graft injury after static, prolonged cold preservation and reperfusion in an isolated model. Methods: Eighteen Sprague-Dawley(SD) heart donor rats were equally divided into two groups: AICAR pretreatment group(AICAR group, n=9) and normal saline pretreatment group(Vehicle group, n=9). After the hearts were arrested with Histidine-Tryptophan-Ketoglutarate(HTK) solution, they were excised and preserved in HTK solution for 8 hours at 4 <sup style=“font-family: Arial, sans-serif;”>o[/sup]C. After cold preservation, hearts were reperfused for 1hr in an Langendorff model, concerned parameters were examined during and after reperfusion. Result: AICAR pretreated heart showed significantly higher left ventricular developing pressure(LVDP), heart rate(HR), coronary flow(CF) than vehicle pretreated group. Caspase 3 activity and percentage of TUNEL-positive cells were significantly reduced in AICAR pretreated group. Oxidative parameter 8-hydroxy-2′-deoxyguanosine(8-OHdG) and malondialdehyde (MDA) were also significantly decreased in AICAR pretreated group. Moreover, AICAR pretreatment significantly diminished cystolic cytochrome C release. Conclusion: Pretreatment of the donor with AICAR significantly protects heart grafts from prolonged cold ischemia/reperfusion injury. This protocol may be useful and feasible in clinical heart transplantation.