Combination of inhaled nitric oxide with iv nitroglycerin or with a prostacyclin analogue in the treatment of experimental pulmonary hypertension

We have studied the effect of combining inhaled nitric oxide (NO) with an i.v. vasodilator agent, nitroglycerin, or ciloprost, a prostacyclin analogue, during acute pulmonary hypertension in pigs, induced by continuous infusion of a thromboxane analogue (U46619), adjusted to maintain mean pulmonary artery pressure (MPAP) at 40 mm Hg. The effects of the different treatments on MPAP and pulmonary resistances were determined. In the first part of the study, we determined the dose-response to increased NO concentrations from 5 to 40 ppm. This showed a maximum pulmonary effect with NO 5 ppm, but with no systemic effects. The effect of NO 10 ppm was then compared with two i.v. drugs. Nitroglycerin was less effective than NO on pulmonary vessels but induced significant arterial hypotension. Pulmonary vasodilatation induced by ciloprost was greater than that by NO but with the same side effects as nitroglycerin on systemic variables. We also found that the combination of NO and nitroglycerin had the same pulmonary effects as NO 10 ppm but that adding ciloprost to NO decreased pulmonary pressures significantly more than either drug used alone. We conclude that inhaled NO may be usefully combined with i.v. ciloprost but not with i.v. nitroglycerin.