title: Intracarotid nitroprusside does not augment cerebral blood flow in human subjects.
abstract: BACKGROUND
  The recent resurgence of interest in the cerebrovascular effects of nitroprusside can be attributed to the possibility of using nitric oxide donors in treating cerebrovascular insufficiency. However, limited human data suggest that intracarotid nitroprusside does not directly affect cerebrovascular resistance. In previous studies, physiologic or pharmacologic reactivity of the preparation was not tested at the time of nitroprusside challenge. The authors hypothesized that if nitric oxide is a potent modulator of human cerebral blood flow (CBF), then intracarotid infusion of nitroprusside will augment CBF.
  
  
  METHODS
  Cerebral blood flow was measured (intraarterial (133)Xe technique) in sedated human subjects undergoing cerebral angiography during sequential infusions of (1) intracarotid saline, (2) intravenous phenylephrine to induce systemic hypertension, (3) intravenous phenylephrine with intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and (4) intracarotid verapamil (0.013 mg x kg(-1) x min(-1)). Data (mean +/- SD) were analyzed by repeated-measures analysis of variance and post hoc Bonferroni-Dunn test.
  
  
  RESULTS
  Intravenous phenylephrine increased systemic mean arterial pressure (from 83 +/- 12 to 98 +/- 6 mmHg; n = 8; P < 0.001), and concurrent infusion of intravenous phenylephrine and intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with intravenous phenylephrine or with concurrent infusions of intravenous phenylephrine and intracarotid nitroprusside. Intracarotid verapamil increased CBF (43 +/- 9 to 65 +/- 11 ml x 100 g(-1) x min(-1); P < 0.05).
  
  
  CONCLUSIONS
  The authors conclude that, in humans, intracarotid nitroprusside sufficient to decrease mean arterial pressure during recirculation, does not augment CBF. Failure of intracarotid nitroprusside to augment CBF despite demonstrable autoregulatory vasoconstriction and pharmacologic vasodilation questions the significance of nitric oxide-mediated vasodilation in human cerebral circulation.
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. sj121@columbia.edu
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
authors.forename: William L
authors.initials: WL
authors.lastname: Young
authors.forename: Huang
authors.initials: H
authors.lastname: Duong
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Aagaard
authors.forename: Noeleen D
authors.initials: ND
authors.lastname: Ostapkovich
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.forename: John
authors.initials: J
authors.lastname: Pile-Spellman
mesh_terms: D000328:Adult; D000368:Aged; D002339:Carotid Arteries / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D014700:Verapamil