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 μg·kg·min, 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 (Δ%QL-VA) increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0μg·kg·min) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. The change in arterial oxygen tension (ΔPaO2) also increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 μg·kg·min) 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.