Opiate Drugs and δ-Receptor-Mediated Myocardial Protection

Benedict, Patrick E. MD
Benedict, Mary B. MD
Su, Tsung-Ping PhD
Bolling, Steven F. MD

From the University of Michigan Health System (P.E.B., S.F.B.) and St. Joseph Mercy Hospital (M.B.B.), Ann Arbor, Mich; and the National Institutes of Health, Bethesda, Md (T.-P.S.).

Circulation 100(19):p II-360, November 9, 1999.

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 δ-opiate peptides. Furthermore, hibernation-induction triggers extend organ preservation in many models. This study examined whether opiate drugs with an affinity for the δ-opiate receptor confer similar protection.

Methods and Results

Isolated hearts harvested from New Zealand White rabbits were treated with either cardioplegia alone or δ-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 δ-opiate activity confer myocardial protection, which is additive to cardioplegia. Use of δ-opiate drugs in this context may have important clinical implications.