Effect of the H1 blocker d-chlorpheniramine on cerebral blood flow in the conscious dog during normocapnic hypoxia.
The mechanism causing cerebral vasodilatation during hypoxia remains unclear. A role for histamine is suspected because H2 receptor-blocking drugs blunt the hypoxia-induced increase in cerebral blood flow (CBF). Moreover, in vitro blockade of H1 receptors by chlorpheniramine decreases the vasodilatation of cerebral arteries that is induced by histamine. The present study tested the hypothesis that an H1 receptor blocker (d-chlorpheniramine) would have a similar effect in vivo during hypoxia. Isocapnic hypoxia (inspired oxygen fraction, FIO2 = 0.10; inspired carbon dioxide fraction, FICO2 = 0.035) was induced in 16 conscious dogs randomly divided into two groups: eight dogs received saline intravenously (controls) at time 0 (normoxia) and after 2 h and 4 h hypoxia, and the other eight dogs received d-chlorpheniramine intravenously (0.5 mg kg-1) to block the H1 receptors. Regional CBF was measured by the radioactive microspheres technique 15 min after each injection of d-chlorpheniramine or saline. In the control group, CBF increased during hypoxia in all regions of the brain. In the d-chlorpheniramine group, total CBF increased similarly after 2 h of hypoxia. After 4 h of hypoxia, the increase was limited, especially in the pons, cerebral peduncles, hippocampus, hypothalamus, thalamus, and occipital lobes (six out of 12 studied regions). It is concluded that the H1 blocker d-chlorpheniramine did not strongly inhibit the increase in CBF during hypoxia. After cumulative doses, however, as in the fourth hour of hypoxia, the increase in total CBF was limited.
Audibert
G
G
Departement d'Anesthésiologie, Hôpital Central, Nancy, France.
Siat
J
J
Müller
C
C
Hartemann
D
D
Naja
G
G
Saunier
C G
CG
Laxenaire
M C
MC
D000818:Animals; D001784:Blood Gas Analysis; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002744:Chlorpheniramine / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000503:physiopathology*; D008297:Male; D008863:Microspheres
D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine