Halothane and xanthine oxidase increase hepatocellular enzyme release and circulating lactate after ischemia - Reperfusion in rabbits

Background: Multiple-organ injury often occurs after aortic occlusion- reperfusion. Oxidants derived from xanthine oxidase have been implicated as a source of injury after aortic occlusion-reperfusion. Halogenated anesthetics modify oxidant-mediated injury. The current study determined if halothane modifies hepatocellular enzyme release (e.g., alanine aminotransferase) and circulating lactate after aortic occlusion-reperfusion. Methods: Rabbits were randomly assigned to one of four groups that underwent 40 min of thoracic aortic occlusion and 2 h of reperfusion: Two groups were given either halothane or fentanyl plus droperidol anesthesia and two groups were given either anesthetic and sodium tungstate (xanthine oxidase inactivator). Each of the four groups was then matched with a similarly treated group that did not undergo aortic occlusion. Results: Halothane anesthesia was associated with significantly (P < 0.05) increased release of alanine aminotransferase (34 ± 9 U/l at baseline and 539 ± 370 U/l at 120 min of reperfusion; mean ± SD) and increased plasma lactate concentrations (2.8 ± 2.0 mM at baseline and 12.1 ± 9.7 mM at 120 min of reperfusion) after aortic occlusion- reperfusion compared with fentanyl plus droperidol anesthesia (alanine aminotransferase, 33 ± 12 U/l and 148 ± 109 U/l; lactate, 3.4 ± 2.0 mM and 3.8 ± mM at baseline and 120 min of reperfusion, respectively). Inactivation of xanthine oxidase significantly decreased the release of hepatocellular enzymes (p < 0.05) and decreased circulating lactate in animals anesthetized with halothane after aortic occlusion-reperfusion. Conclusions: Halothane increased hepatocellular enzyme release and circulating lactate after aortic occlusion-reperfusion compared with fentanyl plus droperidol anesthesia. Xanthine oxidase activity inactivation also decreased hepatocellular enzyme activity release during reperfusion. These findings justify further investigations to determine if halogenated anesthetics modify tissue injury in clinical settings involving oxidant stress.