CEREBRAL BLOOD-FLOW IN PRIMATES IS INCREASED BY ISOFLURANE OVER TIME AND IS DECREASED BY NITRIC-OXIDE SYNTHASE INHIBITION

Background: Cerebral blood now (CBF) decreases over time in dogs and g oats during volatile anesthesia. In the current study, we determined C BF during administration of isoflurane for 4 h in cynomolgus monkeys. In addition, we determined if nitric oxide (NO) contributes to cerebro vascular tone during isoflurane anesthesia by determining the CBF (mic rosphere) response to inhibition of NO synthase with N-omega-nitro-L-a rginine methyl ester (L-NAME). Methods: CBF was measured in five monke ys anesthetized with isoflurane (1.0% end-tidal). After 4 h of isoflur ane (1.0% = 1 MAC), the effects of intravenous L-NAME (60 mg/kg over 1 0 min) followed by intravenous L-arginine (600 mg/kg over 10 min) on C BF were measured at constant cerebral perfusion pressure and arterial carbon dioxide tension. Results: CBF was unchanged over time (4 h) in cerebellum but increased by 50 +/- 18% in both forebrain and hindbrain (P < 0.05). CBF decreased by 41-48% (P < 0.05) 20 min after L-NAME in forebrain, cerebellum, and hindbrain, at which time brain NO synthase activity was less than 10% of baseline. Twenty minutes after L-argini ne, CBF was increased in cerebellum by 32 +/- 8% and in forebrain by 4 1 +/- 3% (P < 0.05). The cerebral metabolic rate of oxygen consumption was unaffected by time or by L-NAME or L-arginine. Conclusions These data demonstrate that CBF increases over time during isoflurane anesth esia in primates. Tonic production of NO contributes to control of CBF in primates during isoflurane anesthesia. Increased CBF by L-arginine after L-NAME supports the hypothesis that L-NAME decreases CBF via a mechanism requiring NO synthesis.