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The effects of volatile anesthetics on red blood cell flow in the cerebral microcirculation have not been compared. We used laser-Doppler flowmetry, which measures red blood cell flow in the microcirculation to compare the effects of differing concentrations of isoflurane and halothane on cerebrocortical microcirculation. Sprague-Dawley rats were anesthetized with pentobarbital (65 mg/kg intraperitoneally). The animals were tracheotomized, paralyzed, and artificially ventilated. In the first protocol laser-Doppler flow (LDF) was recorded at 0.5,1,1.5, and 2 minimum alveolar anesthetic concentration (MAC) halothane or isoflurane, with blood pressure controlled by intravenous phenylephrine infusion (0.5–5 μg·kg-1·min-1). In the second protocol the effects of 0.5 and 1.5 MAC halothane and isoflurane on LDF changes in response to changes in mean arterial blood pressure (MABP) were compared. MABP was increased by phenylephrine infusion and decreased by hemorrhage. LDF increased with each 0.5 MAC increase in halothane and isoflurane concentration (P < 0.05). LDF was greater at 1.5 and 2 MAC isoflurane than at equi-MAC halothane (P < 0.01). Autoregulation of LDF was present but attenuated at MABP of 60–140 mm Hg at low halothane and isoflurane concentrations. LDF was increased at 1.5 MAC vs 0.5 MAC for both drugs (P < 0.01). The autoregulation coefficients (percent LDF change/mm Hg MABP change) were 0.41 ± 0.10, 0.42 ± 0.07, 0.27 ± 0.04, and 0.20 ± 0.05 at 0.5 MAC halothane, 0.5 MAC isoflurane, 1.5 MAC halothane, and 1.5 MAC isoflurane, respectively. The results of this study suggest that 1) both halothane and isoflurane cause dose-related increases in cerebrocortical LDF with isoflurane having a greater effect at higher concentrations; and 2) autoregulation of LDF is present but attenuated at low concentrations of both anesthetics.