Intermittent nitric oxide combined with intravenous dipyridamole in a piglet model of acute pulmonary hypertension.

Abstract

Continuous administration of inhaled nitric oxide is now widely used as a potent and selective pulmonary vasodilator. We have evaluated the effects of IV dipyridamole, a cyclic guanosine monophosphate (cGMP) phosphodiesterase inhibitor, on the magnitude and duration of action of inhaled nitric oxide (NO)-mediated pulmonary vasodilation. We hypothesized that inhibition of cGMP degradation could augment and prolong the pulmonary vasodilating effects of NO and allow for intermittent NO inhalation. In eight anesthetized and mechanically ventilated piglets, IV U-46619, a thromboxane A(2) analog, was used to induce pulmonary hypertension. The effects of 2, 5, and 10 ppm of NO, delivered during 4 min for each concentration and followed by a 10-min NO-free interval after each NO concentration, were evaluated without and with dipyridamole. Pulmonary vascular resistance decreased from 825 +/- 49 dynes. s. cm(-5) (U-46619) to 533 +/- 48 dynes. s. cm(-5) (10 ppm NO) (P < 0.05 versus U-46619) and 396 +/- 42 dynes. s. cm(-5) (dipyridamole 10 microg kg-1x min-1 and 10 ppm NO) (P <0.05 versus NO), and cardiac output increased from 1.93 +/- 0.09 L/min to 2.03 +/- 0.13 L/min and 2.60 +/- 0.30 L/min (P < 0.05 versus NO). Mean arterial blood pressure decreased from 90 +/- 5 mm Hg (10 ppm NO) to 75 +/- 3 mm Hg (dipyridamole plus 10 ppm NO) (P < 0.01). The pulmonary vasodilation obtained with NO alone could be prolonged from 12 to 42 min when inhaled NO was combined with IV dipyridamole, accounting for a time-weighted reduction in NO exposure by 72%. We conclude that dipyridamole augments the effects of NO on right ventricular afterload, allows for intermittent NO inhalation, and can significantly reduce exposure to NO. IV dipyridamole prolongs the action of inhaled nitric oxide (NO) in a piglet model of acute pulmonary hypertension. Intermittent NO inhalation combined with IV dipyridamole decreases pulmonary artery pressure for a prolonged period of time and reduces exposure to NO.