Prostaglandin E1 antagonizes hypoxic pulmonary vasoconstriction but reduces systemic blood pressure in dogs.

OBJECTIVE

To investigate whether prostaglandin E1 (PGE1) directly inhibits hypoxic pulmonary vasoconstriction in dogs.

DESIGN

Prospective, longitudinal study.

SETTING

University research laboratory.

SUBJECTS

Six mongrel dogs in vivo.

INTERVENTIONS

The left thorax of anesthetized and ventilated dogs was opened and the left lower lobe was separately ventilated. The tip of the thermodilution pulmonary artery catheter was introduced into the left lower lobe pulmonary artery. The left lower lobe was ventilated with hyperoxic (95% oxygen and 5% CO2) or hypoxic (95% nitrogen and 5% CO2) gas. By manipulating the occluders placed on both pulmonary arteries, blood flow in the left lower lobe was regulated. Continuous pressure-flow plots for the left lower lobe were then obtained.

MEASUREMENTS AND MAIN RESULTS

Measurements included continuous pressure-flow plot generation, thermodilution cardiac output and blood flow in the left lower lobe, and blood gas analysis. Alveolar hypoxia of the left lower lobe caused blood flow in the left lower lobe to decrease from 371.8 +/- 63.4 to 95.0 +/- 23.4 mL/min and shifted the pressure-flow plot to the right, with a decreased slope and with an increase in the pressure-axis intercept. Subsequently, systemic venous infusion of PGE1 at a rate of 0.3 microg/kg/min had no effect on the pressure-flow plot configuration, blood flow in the left lower lobe, pulmonary vascular resistance, systemic vascular resistance, and PaO2. However, there was a decrease in the pressure-axis intercept of the pressure-flow plot. Infusion of PGE1 at a rate of 3.0 microg/kg/min (high-dose) during hypoxia reduced pulmonary vascular resistance and systemic vascular resistance by 19% and 25%, respectively, and returned the pressure-flow plot toward normal while blood flow in the left lower lobe increased to 122.6 +/- 21.0 mL/min. Consequently, PaO2 decreased from 270 +/- 31 to 144 +/- 32 torr (36.0 +/- 4.1 to 19.2 +/- 4.3 kPa).

CONCLUSION

High-dose PGE1 essentially inhibits hypoxic pulmonary vasoconstriction, at the expense of a deterioration in pulmonary gas exchange and systemic blood pressure in dogs.