Opiate Drugs and d-Receptor–Mediated Myocardial Protection

Background—Hypothermic myocardial arrest is necessary to complete most cardiac surgery, which limits the success of such operations. Similarly, cold, inhospitable environments limit the survival of warm-blooded animals. Animals have successfully adapted to this challenge through hibernation. Hibernation is an energy-conserving state, now known to be governed by cyclical variation in endogenous opiate compounds. It may also be induced in nonhibernators via hibernating animal serum factors or d-opiate peptides. Furthermore, hibernation-induction triggers extend organ preservation in many models. This study examined whether opiate drugs with an affinity for the d-opiate receptor confer similar protection. Methods and Results—Isolated hearts harvested from New Zealand White rabbits were treated with either cardioplegia alone or d-opiate drugs (fentanyl, morphine, buprenorphine, pentazocine) followed by 2 hours of 34°C ischemia. Hearts were then reperfused, and functional and metabolic indices of treated groups were compared with untreated controls. Isovolumic developed pressure, coronary flow, and oxygen consumption were compared as a percent of preischemia versus 45 minutes after reflow. Developed pressure and oxygen consumption were better preserved in the morphine, buprenorphine, and pentazocine groups when compared with cardioplegia alone. Conclusions—Drugs with d-opiate activity confer myocardial protection, which is additive to cardioplegia. Use of d-opiate drugs in this context may have important clinical implications. (Circulation. 1999;100[suppl II]:II-357–II-360.)