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Cerebral Blood Flow in Primates Is Increased by Isoflurane over Time and Is Decreased by Nitric Oxide Synthase Inhibition.

McPherson, Robert W. M.D.; Kirsch, Jeffrey R. M.D.; Tobin, Joseph R. M.D.; Ghaly, Ramsis F. M.D.; Traystman, Richard J. Ph.D.

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Background: Cerebral blood flow (CBF) decreases over time in dogs and goats during volatile anesthesia. In the current study, we determined CBF during administration of isoflurane for 4 h in cynomolgus monkeys. In addition, we determined if nitric oxide (NO) contributes to cerebrovascular tone during isoflurane anesthesia by determining the CBF (microsphere) response to inhibition of NO synthase with N(R)-nitro-L-arginlne methyl ester (L-NAME).
Methods: CBF was measured in five monkeys anesthetized with isoflurane (1.0% end-tidal). After 4 h of isoflurane (1.0% = 1 MAC), the effects of intravenous L-NAME (60 mg/kg over 10 min) followed by intravenous L-arginine (600 mg/kg over 10 mln) on CBF were measured at constant cerebral perfuslon 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 hlndbrain (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-arglnine, CBF was increased in cerebellum by 32 +/- 8% and in forebrain by 41 +/- 9% (P < 0.05). The cerebral metabolic rate of oxygen consumption was unaffected by time or by L-NAME or L-arglnine.
Conclusions: These data demonstrate that CBF increases over time during isoflurane anesthesia in primates. Tonic production of NO contributes to control of CBF in primates during isoflurane anesthesia. Increased CBF by L-arglnine after L-NAME supports the hypothesis that L-NAME decreases CBF via a mechanism requiring NO synthesis.
(C) 1994 American Society of Anesthesiologists, Inc.
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