Summary: Barbiturates and the volatile anesthetic isoflu rane 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 iso flurane should similarly reduce ischemic injury. To eval uate this, spontaneously hypertensive rats underwent 2 h of reversible middle cerebral artery occlusion (MCAO) while receiving deep methohexital. isoflurane. or halo thane anesthesia. Ninety-six hours postischemia, neuro logic deficits were present but without a difference be tween 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 mm 3 ) than in either the halothane (n = 9; 249 ± 71 mm 3 ; p < 0. 04) or the isoflurane (n = 9; 243 ± 62 mm 3 ; p < 0. 03) groups. One possible explana tion for the lack of protective effect for isoflurane might be related to its vasodilative properties, which could re sult in a cerebral vascular steal. To examine this possi bility, rats anesthetized with methohexital or isofluraneBarbiturates produce a dose-dependent decrease in CMR, having maximal effect at the end-point of EEG burst suppression (Michenfelder, 1974). The same agents have also been demonstrated to pro vide cerebral protection in various animal models of focal ischemia (Smith et ai., 1974; Michenfelder et ai., 1976; Nehls et ai., 1987). The presumed mech anism of this protection is a barbiturate-induced re duction in cerebral metabolic requirements that counterbalances diminished 02/substrate delivery. 794 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 hemi sphere was analyzed for percentage of cross-sectional area where flow was <25 m1l100 g/min, significantly less tissue appeared to be at risk for infarction in the isoflu rane 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 re duction 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 isoflu rane. Key Words: Anesthetics, inhalational and intrave nous-Brain-Cerebral blood flow-Halothane-Iso flurane-Methohexital.
To determine if an acute neurologic injury alters the cerebrovascular response to isoflurane, rabbits were anesthetized with morphine/N2O, mechanically ventilated, surgically instrumented, and assigned to one of three groups. Group 1 animals (n = 8) served as controls and received no injury. In Groups 2 (n = 9) and 3 (n = 8), a 30-s cryogenic injury was produced in the left parietal region using liquid N2 poured into a funnel affixed to the surface of the skull. Regional CBF was measured using microspheres. In Groups 2 and 3, flow was determined before and then 30 and 90 min after injury or at equivalent times in Group 1. After the 90-min data were collected, 1% [approximately 0.5 minimal alveolar concentration (MAC)] and then 2% (approximately 1.0 MAC) isoflurane was administered to uninjured rabbits in Groups 1 and to lesioned rabbits in Group 3. A mean arterial pressure of greater than or equal to 80 mm Hg was maintained during isoflurane administration by an infusion of angiotensin II. In uninjured rabbits (Group 1), 2% isoflurane produced bilaterally symmetrical increases in hemispheric CBF, from 76 +/- 21 (mean +/- SD) to 150 +/- 48 ml 100 g-1 min-1. CBF in the hindbrain increased from 91 +/- 25 to 248 +/- 102 ml 100 g-1 min-1. By contrast, in the lesioned rabbits of Group 3, 2% isoflurane resulted in CBF in the lesioned hemisphere changing from 56 to only 77 ml 100 g-1 min-1 (NS), while in the contralateral hemisphere, CBF rose from 68 to 97 ml 100 g-1 min-1 (also NS). These results indicate that a cryogenic injury attenuates the normal CBF response to a volatile anesthetic, both in the damaged hemisphere as well as in apparently uninjured regions distant from the injury focus. In a separate group of animals, a similar cryogenic injury abolished the CBF response to changing PaCO2 in the injured hemisphere, but not in either the contralateral hemisphere or the cerebellum. It is possible that the CBF effects of isoflurane may be mediated via some intermediary neurogenic and/or biochemical process.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.