Differential Effects of Anesthetic Agents on Outcome from Near-complete but Not Incomplete Global Ischemia in the Rat

Abstract

Background It has been postulated that anesthetic agents that reduce cerebral metabolic rate will protect the brain against ischemia when electroencephalographic (EEG) activity is persistent, but will provide no protection when ischemia is severe enough to cause EEG isoelectricity. No outcome studies have addressed this issue. The authors studied anesthetic agents to determine if they provide differential effects on outcome from global cerebral ischemic insults that cause either an attenuated or isoelectric EEG. Methods Fasted rats were subjected to either (1) incomplete ischemia (attenuated EEG; 20 min of mean arterial pressure [MAP] = 50 mmHg and bilateral carotid occlusion) or (2) near-complete ischemia (isoelectric EEG; 10 min of MAP = 30 mmHg and bilateral carotid occlusion) while anesthetized with 1.4% isoflurane, 1 mg x kg(-1) x min(-1) ketamine, or 25 microg x kg(-1) x h(-1) 70% nitrous oxide and fentanyl. The brain was maintained at normothermia during ischemia and for 22 h after ischemia. Five days later, hippocampal CA1 and cortical injury were measured. Results There was no difference among anesthetic agents during incomplete ischemia for mean +/- SD percentage dead CA1 neurons (fentanyl, 38%+/-20%; isoflurane, 31%+/-10%; ketamine, 40%+/-19%; P = 0.38). During near-complete ischemia, there was a difference among anesthetic agents (fentanyl, 88%+/-9%; isoflurane, 37%+/-20%; ketamine, 70%+/-28%; P = 0.00008). Isoflurane was protective compared with fentanyl (P = 0.00007) and ketamine (P = 0.0061). There was no difference between fentanyl and ketamine (P = 0.143). Similar observations were made in the cortex. Neurologic function correlated with histologic damage. Conclusions Outcome from near-complete but not incomplete cerebral ischemia depended on the anesthetic agent administered during the ischemic insult.