title: Cerebral blood flow in primates is increased by isoflurane over time and is decreased by nitric oxide synthase inhibition.
abstract: 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 omega-nitro-L-arginine 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 min) on CBF 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-arginine, 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-arginine.
  
  
  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-arginine after L-NAME supports the hypothesis that L-NAME decreases CBF via a mechanism requiring NO synthesis.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: R W
authors.initials: RW
authors.lastname: McPherson
authors.forename: J R
authors.initials: JR
authors.lastname: Kirsch
authors.forename: J R
authors.initials: JR
authors.lastname: Tobin
authors.forename: R F
authors.initials: RF
authors.lastname: Ghaly
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D011659:Pulmonary Gas Exchange; D013874:Thiopental; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D013874:Thiopental; D019331:NG-Nitroarginine Methyl Ester