Analysis of airway effects of a PGH ₂ analog in the aesthetized dog

The effects of PGH ₂ analog, (15S)-hydroxyl-11α,9α-(epoxymethano)prosta-5Z, 13E-dienoic acid, on pulmonary mechanics were studied in the anesthetized and paralyzed closed-chest dog under conditions of controlled ventilation. Injection of the analog into the right side of the heart produced a dose- related increase in lung resistance (RL) and decrease in dynamic lung compliance (Cdyn). Lung volume at end-passive expiration decreased during the peak of the response, as did specific conductance and specific compliance. Static compliance was reduced to the same extent as Cdyn. The decrease in compliance was temporally associated with a sharp rise in pulmonary arterial pressure (Ppa). Arterial oxygen tensions were unchanged. Left ventricular administration produced qualitatively similar effects on lung mechanics, which were attenuated and delayed. Changes in RL, Cdyn, and Ppa were not affected by vagotomy. Experiments in which the effects of the analog and passive increases in pulmonary venous pressure were compared suggest that not more than 25% of the compliance decrease could be due to pulmonary vascular congestion. These data suggest that the analog is highly active in both airways and pulmonary vascular bed. Effects on lung mechanics appear to be due to direct constriction by the analog of smooth muscle in the most peripheral and central conducting airways.