DIFFERENTIAL-EFFECTS OF ANESTHETIC AGENTS ON OUTCOME FRONT NEAR-COMPLETE BUT NOT INCOMPLETE GLOBAL-ISCHEMIA IN THE RAT

Background: It has been postulated that anesthetic agents that reduce cerebral metabolic rate will protect the brain against ischemia when e lectroencephalographic (EEG) activity is persistent, but will provide no protection when ischemia is severe enough to cause EEG isoelectrici ty. 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 at tenuated or isoelectric EEG. Methods: Fasted rats were subjected to ei ther (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 bilate ral carotid occlusion) while anesthetized with 1.4% isoflurane, 1 mg.k g(-1)min(-1) ketamine, or 25 mu g.kg(-1)h(-1) 70% nitrous oxide and fe ntanyl, The brain was maintained at normothermia during ischemia and f or 22 h after ischemia. Five days later, hippocampal CA1 and cortical injury were measured. Results: There was no difference among anestheti c agents during incomplete ischemia for mean I SD percentage dead CA1 neurons (fentanyl, 38% +/- 20%; isoflurane, 31% +/- 10%; ketamine, 40% +/- 19%; P = 0.38). During near-complete ischemia, there was a differ ence among anesthetic agents (fentanyl, 88% +/- 9%; isoflurane, 37% +/ - 20%; ketamine, 70% ii 28%; P = 0.00008), Isoflurane was protective c ompared with fentanyl (P = 0.00007) and ketamine (P = 0.0061). There w as no difference between fentanyl and ketamine(P = 0.143). Similar obs ervations were made in the cortex, Neurologic function correlated with histologic damage. Conclusions: Outcome from near-complete but not in complete cerebral ischemia depended on the anesthetic agent administer ed during the ischemic insult.