title: Intra-arterial 133Xe measurements suggest a dose-dependent increase in cerebral blood flow during intracarotid infusion of adenosine in nonhuman primates.
abstract: Intra-arterial vasodilators, such as papaverine, have been used to treat cerebrovascular insufficiency. The short biologic half-life, and the vasodilating and neuroprotective properties of adenosine could be useful during the treatment of cerebral ischemia. However, in human subjects a proposed intracarotid dose of 1 mg/min adenosine was ineffective in augmenting cerebral blood flow (CBF). The object of this experiment was to determine the dose-CBF response characteristics of intracarotid adenosine in nonhuman primates. Studies were conducted on five male baboons under isoflurane anesthesia. After transfemoral internal carotid artery cannulation, changes in CBF (intra-arterial 133Xe technique) were determined after intracarotid infusion of saline and three increasing doses of adenosine (0.5, 1.0, and 1.5 mg/min). Each infusion lasted 5 minutes. Data (mean +/- standard deviation) were analyzed by repeated-measure analysis of variance and the post hoc Tukey test. Intracarotid adenosine (0.5, 1.0, and 1.5 mg/min) resulted in a dose-dependent increase in CBF from 22.6 +/- 4 mL/100 g/min at baseline to 50 +/- 15, 65 +/- 22, and 83 +/- 31 mL/100 g/min respectively (n = 5, P < .05 each). No adverse hemodynamic side effects were noted, and animals recovered promptly from anesthesia. The authors conclude that intracarotid adenosine in the range of 0.5 to 1.5 mg/min results in a robust increase in CBF. Based on body weight, intracarotid adenosine in a dose range of 2.5 to 7.5 mg/min may be required to augment CBF in human subjects.
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
authors.forename: Sundeep
authors.initials: S
authors.lastname: Mangla
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Robert R
authors.initials: RR
authors.lastname: Sciacca
authors.forename: William L
authors.initials: WL
authors.lastname: Young
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002339:Carotid Arteries / Q000502:physiology*; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D010215:Papio; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014978:Xenon; D014980:Xenon Radioisotopes
chemical_list: D014665:Vasodilator Agents; D014980:Xenon Radioisotopes; D014978:Xenon; D000241:Adenosine