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

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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.