HALOTHANE PREVENTS POSTISCHEMIC PRODUCTION OF HYDROXYL RADICALS IN THE CANINE HEART

Background: Recent studies indicate that during regional myocardial is chemia and subsequent reperfusion, volatile anesthetics may provide pr otection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the can ine heart, was investigated. The level of hydroxyl radical ((OH)-O-.)- mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored. Methods: Under general anesthe sia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterio r descending artery occlusion. Six dogs were studied using inhaled hal othane (1.6%) 10 min before and during the 10-min ischemic period, fol lowed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3- DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored. Results: An acute increase in the normalized concentrations of 2,3-DH BA and 2,5-DHBA was observed in the control animals during reperfusion . In contrast, halothane inhalation completely inhibited the productio n of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the h alothane-treated group were even less than the basal level (P < 0.05). The increase in lactate concentrations in the experimental animals wa s significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane si gnificantly decreased (P < 0.0001) the difference in oxygen content be tween coronary sinus and aortic root blood, suggesting decreased oxyge n utilization during reperfusion. Conclusions: Halothane completely in hibited the production of (OH)-O-., and its administration may protect the heart from the deleterious effect of oxygen-derived reactive spec ies, with attenuation of the metabolic response to ischemia.