Reversible Focal Ischemia in the Rat: Effects of Halothane, Isoflurane, and Methohexital Anesthesia

Abstract

Barbiturates and the volatile anesthetic isoflurane reduce CMR to similar values. If the mechanism of barbiturate protection against focal ischemic injury is due to a reduction in cellular energy requirements, then isoflurane should similarly reduce ischemic injury. To evaluate this, spontaneously hypertensive rats underwent 2 h of reversible middle cerebral artery occlusion (MCAO) while receiving deep methohexital, isoflurane, or halothane anesthesia. Ninety-six hours postischemia, neurologic deficits were present but without a difference between groups. Mean ± SD infarct volume, as assessed by triphenyl tetrazolium chloride staining and computerized planimetry, was significantly less in the methohexital group (n = 8; 166 ± 74 mm3) than in either the halothane (n = 9; 249 ± 71 mm3; p < 0.04) or the isoflurane (n = 9; 243 ± 62 mm3; p < 0.03) groups. One possible explanation for the lack of protective effect for isoflurane might be related to its vasodilative properties, which could result in a cerebral vascular steal. To examine this possibility, rats anesthetized with methohexital or isoflurane underwent autoradiographic determination of CBF with or without MCAO. In isoflurane-anesthetized sham rats (n = 5; no ischemia), CBF was approximately three times greater than in methohexital-treated (n = 5) sham rats. During ischemia, although a regional reduction in flow was noted in both anesthetic groups, mean flow remained greater in the isoflurane group. When the ischemic hemisphere was analyzed for percentage of cross-sectional area where flow was <25 ml/100 g/min, significantly less tissue appeared to be at risk for infarction in the isoflurane group (n = 7; 32.9 ± 19.4%) versus the methohexital group (n = 8; 49.1 ± 12.6%; p < 0.05). These results are consistent with the following conclusions: (a) CMR reduction is not a sufficient criterion for anesthetic-mediated brain protection; (b) isoflurane does not cause cerebrovascular steal; and (c) ischemic flow thresholds for infarction are different for methohexital and isoflurane.