The effect of
almitrine bismesylate on the hypoxic pulmonary
vasoconstrictor (HPV) response was studied in seven closed-chest dogs anesthetized with
pentobarbital and paralyzed with
pancuronium. The right lung was ventilated continuously with 100% O2, while the left lung was ventilated with either 100% O2 ("
hyperoxia") or with an
hypoxic gas mixture ("
hypoxia": end-tidal PO2 = 50.1 +/- 0.1 mmHg). Cardiac output (CO) was altered from a "normal" value of 3.10 +/- 0.18 l . min-1 to a "high" value of 3.92 +/- 0.16 l . min-1 by opening arteriovenous fistulae which allowed measurements of two points along a pressure-flow line. These four phases of left lung
hypoxia or
hyperoxia with normal and
high cardiac output were repeated in the presence and absence of
almitrine.
Almitrine bismesylate was administered as a constant infusion of 14.3 micrograms . kg-1 . min-1 for a mean plasma concentration of 219.5 +/- 26.4 ng . ml-1. Relative blood flow to each lung was measured with a differential CO2 excretion (VCO2) method corrected for the Haldane effect. With both lungs hyperoxic, the percent left lung blood flow (%QL-VCO2) was 44 +/- 1%. When the left lung was exposed to
hypoxia, the %QL-VCO2 decreased significantly to 22 +/- 1%. However, with the administration of
almitrine, the %QL-VCO2 during left lung
hypoxia increased significantly to 36 +/- 2%. The arterial
oxygen tension decreased significantly between
hyperoxia (PaO2 = 633 +/- 6 mmHg) and
hypoxia (271 +/- 31 mmHg). With the addition of
almitrine, there was no change during
hyperoxia; however, during
hypoxia, the PaO2 decreased significantly to 124 +/- 15 mmHg. Cardiac output did not influence these findings. The pulmonary vascular conductance (G) is the slope of the pressure-flow line.(ABSTRACT TRUNCATED AT 250 WORDS)