A COMPARISON OF THE CEREBRAL PROTECTIVE EFFECTS OF ISOFLURANE AND MILD HYPOTHERMIA IN A MODEL OF INCOMPLETE FOREBRAIN ISCHEMIA IN THE RAT

The present study was undertaken to examine the cerebral protective properties attributed to isoflurane and at the same time to compare its protective effects with those of mild hypothermia (temperature reduction by 3-degrees-C). Twenty-one fasted Wistar-Kyoto rats were assigned to one of three groups (n = 7): 1.3 MAC (end-tidal) isoflurane-normothermia (pericranial temperature 38.0-degrees-C), 1.3 MAC halothane-normothermia, and 1.3 MAC halothane-hypothermia (pericranial temperature 35.0-degrees-C during ischemia). In each animal the trachea was intubated and the lungs were mechanically ventilated. Each animal was subjected to temporary incomplete forebrain ischemia induced by 10 min of bilateral carotid artery occlusion with simultaneous hypotension (mean arterial pressure 35 mmHg) induced by trimetaphan and blood withdrawal. After a 3-day survival period, perfusion-fixation was performed, and two blinded observers assessed histopathologic injury according to a four-point scale (0 = no damage; 1 = < 10% of neurons damaged; 2 = 10-50% damaged; and 3 = > 50% damaged). The assessment was performed at two points in the rostrocaudal axis chosen to permit evaluation of regions with varying levels of ischemic damage. In the rostral sections, in the isoflurane- and halothane-normothermia groups, moderate to severe injury was observed in striatum, cerebral cortex, hippocampus (CA1 and CA3 areas), and reticular nucleus of the thalamus (e.g., the median scores for the CA1 area were 3 in both the halothane-normothermia and the isoflurane-normothermia groups), and there were no differences between the two groups. By contrast, the halothane-hypothermia group showed significantly less damage (e.g., the median score for the CA1 area was 1) in all but the hippocampal CA3 area. In the caudal section, the injury was significantly less severe in portions of the cortex and hippocampal CA1. As in the rostral sections, the degree of damage did not differ between the two normothermia groups, but was significantly less severe in the halothane-hypothermia group. The data indicate that in the circumstances of the present study, isoflurane did not confer protection relative to control animals anesthetized with an equipotent concentration of halothane, but that mild intraischemic hypothermia (by 3-degrees-C) was markedly protective.