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Regional (frontal, parietal, occipital, cortical, and basal ganglia) cerebral blood flow (rCBF) was examined at 1.5 and 3.5 MAC inspired isoflurane/O2 anesthesia in the rat using the radioactive microsphere technique to determine the effects of controlled hypotension with deep isoflurane anesthesia on rCBF and the response of rCBF to changes in Paco2 when mean blood pressure (BP) was decreased to levels below the lower limit of the autoregulatory threshold. Four groups of six rats were studied with rCBF 1 determined at 1.5 MAC (mean BP 80–90 mm Hg) followed by two rCBF determinations at 3.5 MAC (mean BP 46–48 mm Hg). For CBF 1 the regional CO2 response was a 3.1–3.9% increase in rCBF/mm Hg increase in CO2- Regional cerebral blood flow (ml/g/min) ranged from 0.64 ± 0.05–0.83 ± 0.15 at Paco2 of 19 mm Hg to 1.34 ± 0.11–1.80 ± 0.33 at Paco2 of 41 mm Hg to 2.61 ± 0.26–3.72 ± 0.37 at Paco2 of 59 mm Hg (mean ± SEM). With controlled hypotension (CBF 2) rCBF was unchanged during normo-carbia, increased 100% during hypocarbia, P < 0.01 vs CBF 1 and decreased 30% during hypercarbia, P < 0.01 vs CBF 1. For rCBF 3 measurements, the BP and inspired concentration of isoflurane were kept constant, while Paco2 was increased in two and decreased in two of the four groups. Within-group comparisons between rCBF 2 and rCBF 3 results demonstrated loss of CO, responsiveness of the rat cerebrovasculature in every region during controlled hypotension to below the autoregulatory threshold at3.5 MAC isoflurane/O2 anesthesia. These results show that rCBF is well maintained in normal cerebral tissue when mean BP is decreased to below the autoregulatory threshold during controlled hypotension with deep isoflurane anesthesia.