THE USE OF HIBERNATION INDUCTION TRIGGERS FOR CARDIAC TRANSPLANT PRESERVATION

Cardiac transplant is hindered by donor shortage and preservation time , Extended extracorporeal preservation could increase the number and d istribution of hearts for transplantation. Interestingly, mammalian hi bernation biology closely parallels the altered cardiac cellular physi ology noted with hypothermic organ storage. The present study undertoo k to test whether treatment with hibernation induction triggers could improve myocardial functional recovery following prolonged ischemic st orage in a nonhibernating mammalian model. To study this hypothesis, i solated rabbit hearts had baseline functional and metabolic parameters recorded and then received either hypothermic storage only or standar d cardioplegia, or cardioplegia containing 1 mg/kg D-Ala2-Leu5-enkapha lin (DADLE), which mimics natural hibernation, or preperfusion with DA DLE, administered for 15 min at 2 mmol, 25 min prior to cardioplegic i schemia. Hearts were then subjected to 18 hr of global ischemic storag e at 4 degrees C. Isovolumic developed pressure, coronary flows, and m yocardial oxygen consumption were significantly improved with DADLE pr etreatment vs. all groups after storage and reflow. Furthermore, DADLE hearts demonstrated better histological ultrastructure preservation f ollowing prolonged storage ischemia. This study demonstrates that hibe rnation protection with DADLE is beneficial for prolonged cardiac stor age. The use of hibernation induction triggers is promising for organ preservation and deserve further mechanistic study.