HIBERNATION TRIGGERS AND MYOCARDIAL PROTECTION

Background-Hypothermic cardioplegia provides myocellular protection, y et postischemic dysfunction remains a significant problem. Interesting ly, the subcellular changes in hibernation parallel the altered biolog y of induced cardiac ischemia but are well tolerated by hibernated mam malian myocardium. An uncharacterized factor derived from hibernating animals, hibernation induction trigger (HIT), has been shown to induce hibernation in active animals and afford myocardial protection after ischemia-reperfusion injury. Therefore, it was of interest to further characterize the cardioprotective effects of HIT in the setting of isc hemia-reperfusion injury. Methods and Results-To determine whether HIT could improve myocardial recovery after global ischemia, isolated rab bit hearts received either standard cardioplegia or HIT in the cardiop legia or underwent preperfusion with HIT before cardioplegia. Alternat ively, to determine whether HIT requires metabolic alteration, additio nal rabbits had in vivo pretreatment with HIT from 15 minutes to 5 day s before ischemia. All hearts underwent 2 hours of global ischemia at 34 degrees C. Recovery of postischemic isovolumic developed pressure, coronary flows, and Mvo(2) Were compared. Compared with vehicle pretre atment, HIT pretreatment (1 hour) significantly enhanced indexes of fu nctional recovery, including developed pressure (38+/-3 versus 69+/-7 mmHg) and coronary flow (46+/-3 versus 82+/-11 mL/min). In addition, u ltrastructural morphology was preserved but only with in vivo pretreat ment. Liver protein content was not increased in rabbits treated from 12 hours to 5 days with HIT versus controls, belying a protein neosynt hesis mechanism. However, the temporal sequences suggested conversion of an inactive HIT prefactor to an active form. Conclusions-Administra tion of serum derived from hibernating black bears to rabbits affords protection against ischemia-reperfusion injury compared with vehicle ( saline)-treated animals in a rabbit isolated heart preparation. It is apparent that HIT deserves further identification and mechanistic stud y in the setting of ischemia-reperfusion injury.