Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange.

To investigate the relationship between hypoxic pulmonary vasoconstriction and respiratory and metabolic acidosis and respiratory alkalosis, the pulmonary gas exchange and pulmonary hemodynamic responses were measured in anesthetized, paralyzed, and mechanically ventilated dogs in two sets of experiments (series A, n = 6; series B, n = 10). The animals were treated with acute hypoxia, CO2 inhalation, hyperventilation, and dinitrophenol in various combinations. Multiple regression analysis indicated that mean pulmonary arterial pressure (Ppa) was significantly correlated with end-tidal PO2, mixed venous PO2, and the mean pulmonary capillary pH (average of arterial and mixed venous pH) as independent variables [series A: r = +0.999, standard error of estimate (SEE) = 0.4 mmHg; series B: r = +0.98, SEE = 1.4 mmHg]. Similar analyses of mean values published by other authors from an acute study on humans with exercise at sea level and simulated altitudes of 10,000 and 15,000 ft also indicated a good relationship (n = 14, r = +0.98, SEE = 2.1 mmHg). The mean data (n = 19) obtained in Operation Everest II at various exercise loads and simulated altitudes gave a correlation of r = +0.87, SEE = 6.1 mmHg. These empirical analyses suggest that variations in the rise of Ppa with hypoxia can be accounted for in vivo by the superimposed acid-base status. Furthermore, ventilation-perfusion inhomogeneity, as estimated in the dogs from end-tidal and arterial O2 and CO2 differences and assuming no true shunt or diffusion impairment, was highly correlated with Ppa and mean pulmonary capillary pH (r = +0.999 in series A, r = +0.77 in series B). The human data from the above studies also showed significant correlations between Ppa and directly measured ventilation-perfusion (standard deviation of perfusion obtained from inert gas measurements). These observations indicate that the beneficial effects of hyperventilation during hypoxia may be related to the marked alkalosis that serves to reduce Ppa and improve pulmonary gas exchange efficiency.

Effects of pentoxifylline on pulmonary hemodynamics during acute hypoxia in anesthetized dogs.

The effects of pentoxifylline on pulmonary hemodynamics were studied in anesthetized dogs during acute alveolar hypoxia. In Series A, 7 dogs received pentoxifylline orally (18 mg/kg/day) for 11 wk and 7 untreated dogs served as control animals. During anesthesia and controlled ventilation, acute alveolar hypoxia was induced (10 to 13% inspired O2) and pulmonary and systemic hemodynamic and blood rheologic measurements were compared with normoxia. In control dogs, cardiac index did not change during hypoxia, but pulmonary vascular resistance index (PVRI) increased 79%, erythrocyte filterability decreased significantly (p less than 0.05), and relative viscosity of blood corrected for hematocrit did not change. In the pentoxifylline-treated dogs, cardiac index increased 28% and PVRI increased only 20%; in contrast to the control dogs, relative viscosity of blood was decreased by 18% and no significant changes in filterability were observed. The increase in PVRI in relation to the drop in arterial O2 saturation was significantly larger (p less than 0.05) in the control dogs. Pentoxifylline also increased P50 by 2.8 mm Hg (p less than 0.05). In Series B, hemodynamic measurements were made during variations in blood flow (induced by restricting venous return) in 3 treated (26 mg/kg/day for 3 wk) and 3 control dogs. In these experiments, pulmonary artery pressure was significantly lower at comparable flows during both normoxia and hypoxia. In both studies, the hemodynamic effects of the drug on the systemic circulation were less than on the pulmonary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)