PREMEDICATION WITH THE OPIOID ANALGESIC BUTORPHANOL RAISES THE THRESHOLD FOR ISCHEMIC PRECONDITIONING IN DOGS

Elucidation of the subcellular mechanism of myocardial ischemic precon ditioning should be facilitated by precise knowledge of the biology of the cardioprotective response. Any proposed molecular mechanism for p reconditioning must be initiated during the required ischemic stress p eriod. The studies reported in this paper were undertaken to determine whether the infarct-limiting effect of four 5-min episodes of ischemi a interspersed by reperfusion can be achieved by a single 5-min episod e. Adult open chest mongrel dogs, premedicated with the analgesic buto rphanol, and anesthetized with sodium pentobarbital, underwent occlusi on of the circumflex coronary artery for 60 min, followed by reperfusi on for 3 h. Treated dogs were preconditioned with one, two or four cyc les of 5-min occlusion followed by reperfusion. Additional dogs, not p remedicated with butorphanol, were either untreated (not preconditione d) or preconditioned with one cycle of ischemia. Infarcts were identif ied using triphenyl-tetrazolium chloride (TTC) macrochemistry and infa rct size (as % of area-at-risk, AAR) was measured and analyzed (using analysis of covariance [ANCOVA]) with respect to coronary collateral b lood flow (measured using radioactive microspheres). Four 5-min cycles of preconditioning ischemia markedly limited infarct size. Two cycles were as effective as four. In contrast, infarct size was not differen t from control infarct size after a single episode of preconditioning ischemia. However, when pentobarbital anesthesia was used without prem edication with butorphanol, a single 5-min ischemic stress did induce cardioprotection. Thus, the ischemic stress required for myocardial pr econditioning in dogs is dependent on the anesthetic and premedication protocol employed. A single 5-min stimulus is effective in dogs anest hetized with pentobarbital. Premedication with the opioid analgesic, b utorphanol,increases the threshold for induction of cardioprotection.