A comparison of cerebral ischemic flow thresholds during halothane/N₂O and isoflurane/N₂O anesthesia in rats

Isoflurane/N₂O anesthesia has been reported to reduce the cerebral blood flow (CBF) threshold at which electroencephalographic changes occur in humans during carotid occlusion (when compared to halothane/N₂O). To further evaluate this observation, normocapnic, normothermic rats were anesthetized with 0.75 MAC isoflurane or halothane in combination with 60% N₂O. The electrocorticogram (ECoG) and the cortical DC potential were recorded using glass microelectrodes. Both carotid arteries were occluded, and mean arterial pressure (MAP) was reduced over 3-5 min (by phlebotomy) to predetermined values between 30 and 75 mmHg. This MAP was maintained for 10 min, and CBF was then measured in cortical gray matter using [³H]-nicotine. Flows were then correlated with ECoG changes and with the presence or absence of cortical depolarization (which reflects the loss of transmembrane ion homeostasis). In other rats, the cortical cerebral metabolic rate for glucose (CMR(glu)) was determined autoradiographically using [¹⁴C]-deoxyglucose. Finally, the time to depolarization was determined in rats killed with KCl and in rats subjected to hypotension (MAP = 30-35 mmHg) followed by abrupt bilateral carotid occlusion. The distributions of CBF values in the anesthetic groups were essentially identical. The incidence of either major ECoG changes or isoelectricity did not differ between anesthetics. The CBF associated with major ECoG changes (excluding isoelectricity) were 35 ± 12 and 39 ± 18 ml·100 g^-1·min^-1 in the halothane/N₂O and isoflurane/N₂O groups respectively (mean ± SD, difference not significant [NS]). Isoelectricity was seen at 7 ± 4 ml·100 g^-1·min^-1 (median = 6.5) with halothane/N₂O and 17 ± 19 ml·100 g^-1·min^-1 (median = 11) with isoflurane/N₂O (again, NS). The incidence of sustained depolarization did not differ between anesthetics (9 of 25 for halothane/N₂O, 8 of 24 with isoflurane/N₂O). CBF associated with sustained depolarization was 13 ± 12 ml·100 g^-1·min^-1 (median = 10) with halothane/N₂O, compared with 9 ± 6 ml·100 g^-1·min^-1 (median = 9) for isoflurane/N₂O (NS). In rats subjected to cardiac arrest, the time to depolarization was longer with isoflurane/N₂O (102 ± 19 s vs. 77 ± 7 s). In rats subjected to carotid occlusion at a MAP = 30-35 mmHg, the time to depolarization was again longer with isoflurane/N₂O (210 ± 78 s vs. 122 ± 44 s). Cortical CMR(glu) was lower with isoflurane/N₂O (25 ± 5 μmol·100 g^-1·min^-1) than with halothane (43 ± 13 μmol·100 g^-1·min^-1, P = 0.03). The results indicate that isoflurane/N₂O anesthesia delays the onset of ischemic cell depolarization. However, when ischemia was prolonged for 10 min, we found no differences in either the incidence of sustained depolarization or the CBF values associated with depolarization.