Effects of H2-receptor blockers on response of cerebral blood flow to normocapnic hypoxia.
Cimetidine blunts the increase in cerebral blood flow (CBF) normally observed during hypoxia. It is important, therefore, to know whether other H2-blockers also affect the cerebral circulation adaptation to hypoxia. Cerebral blood flow was measured in 24 awake dogs after an intravenous injection of either saline (control) or one of three H2-blockers: 1 mg/kg ranitidine, 0.4 mg/kg famotidine, or 1 mg/kg roxatidine. These doses are equipotent blockers of H2-gastric receptors. Each dog was studied during normoxia and after 2 and 4 h of normocapnic hypoxia (FIO2, 0.10; FICO2, 0.035). During each set of experimental conditions, a bolus of either saline or one of the anti-H2 drugs was administered, and, 15 min later, radiolabeled microspheres (ruthenium 103, scandium 46, and cerium 141) were injected into the left atrium for measurement of regional CBF. After death by an overdose of thiopental, each dog's brain was excised and fixed in 10% formaldehyde; it was then weighed and dissected by region, with the radioactivity measured in each region using a gamma counter. During hypoxia, PaO2 ranged from 45 to 50 mm Hg, and pH, PaCO2, and hematocrit were within the normal limits. In the control group CBF increased 34% above normoxic baseline levels after 2 h and 31% after 4 h of hypoxia. Ranitidine (1 mg/kg) did not prevent the increase in CBF during hypoxia, but famotidine and roxatidine prevented it. When the dose of ranitidine was doubled (2 mg/kg), it too abolished the increase of CBF induced by hypoxia. In conclusion, H2-receptor blockers could interfere with the adaptation of CBF during hypoxia.
Audibert
G
G
INSERM U14, Vandoeuvre-les-Nancy, France.
Saunier
C
C
Hartemann
D
D
Bigard
O
O
Haberer
J P
JP
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004285:Dogs; D015738:Famotidine / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D007275:Injections, Intravenous; D008863:Microspheres; D010880:Piperidines / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011899:Ranitidine / Q000494:pharmacology*; D012119:Respiration
D006635:Histamine H2 Antagonists; D010880:Piperidines; D015738:Famotidine; D011899:Ranitidine; C053742:roxatidine acetate