Low-dose almitrine bismesylate enhances hypoxic pulmonary vasoconstriction in closed-chest dogs.
The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor response was studied in six closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2; the left lung was ventilated either with 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal oxygen tension = 60.3 +/- 0.6 mm Hg). On two consecutive days, each dog received either almitrine (Vectarion, Servier Lab) or malic acid. Consecutive almitrine doses of 0.003, 0.03, 0.3, and 3.0 micrograms.kg-1.min-1, or the equivalent volumes of malic acid without almitrine, were administered intravenously as a constant peripheral infusion for 15 min. Percent blood flow to each lung was calculated based on a variation of the traditional shunt equation. The change in percent left lung blood flow (delta %QL-VA) increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. The change in arterial oxygen tension (delta PaO2) also increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. It is concluded that in dogs low-dose almitrine enhances hypoxic pulmonary vasoconstriction and that this enhancement is dose-related.
Chen
L
L
Center for Research in Anesthesia, University of Pennsylvania School of Medicine, Philadelphia 19104.
Miller
F L
FL
Clarke
W R
WR
Clergue
F X
FX
Marshall
C
C
Marshall
B E
BE
D015765:Almitrine / Q000008:administration & dosage*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D007262:Infusions, Intravenous; D008168:Lung / Q000098:blood supply*; D008293:Malates / Q000008:administration & dosage; D013268:Stimulation, Chemical; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D008293:Malates; C030298:malic acid; D015765:Almitrine