Sympathetic ganglionic blockade masks beneficial effect of isoflurane on histologic outcome from near-complete forebrain ischemia in the rat

Background Isoflurane-anesthetized rats have better outcome from global cer ebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentration s depend on the anesthetic agent and whether sympathetic gandionic blockade affecrs anesthetic-mediated differences in outcome from near-complete fore brain Ischemia. Methods: For two different experiments, normothermic Sprague-Dawley rats th at had fasted were assigned to one of four groups and subjected to 10 min o f 30 mmHg mean arterial pressure and bilateral carotid occlusion, Rats were anesthetized with 1.4% isoflurane or fentanyl (25 mu g kg(-1) h(-1)) and 7 0% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given in travenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days aft er ischemia, Results: In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P< 0.01), Trimethaphan blocked a ll changes in plasma catecholamine concentrations (P < 0.02), In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 n eurons compared with fentanyl-nitrous oxide (43 +/- 22% vs. 87 +/- 10%; P < 0.001). Trimethaphan abolished the beneficial effects of isoflurane (91 +/ - 6%:; P< 0.001). similar observations were made in the cortex. Conclusions: Isoflurane attenuated the peripheral sympathetic response to i schemia and improved histologic outcome compared with fentanyl and nitrous oxide. This outcome benefit was reversed by sympathetic ganglionic blockade . The beneficial effects of isoflurane may result from a neuroprotective in fluence of an intermediate sympathetic response that is abolished by trimet haphan.