Vasodilator therapy in microembolic porcine pulmonary hypertension

The hemodynamic effects of prostaglandin E₁, sodium nitroprusside (SNP), nitroglycerin, and hydralazine were studied in a porcine model of elevated pulmonary vascular resistance (PVR) due to glass bead microembolization (60-150-μm diameter). Each animal received all four drugs. Each drug was titrated to produce a 30% reduction in mean systemic arterial pressure. Although all four drugs decreased PVR, distinct differences in the hemodynamic profiles of the four drugs were evident. Prostaglandin E₁ produced the largest reduction in mean pulmonary artery pressure (from 41 ± 1 to 32 ± 9 mm Hg, mean ± SEM) and PVR (25 ± 3 to 18 ± 2 mm Hg·L^-1·min^-1), and did not affect the ratio of PVR to systemic vascular resistance (PVR/SVR). Sodium nitroprusside and nitroglycerin produced moderate decreases in PVR (nitroglycerin 21 ± 2 to 18 ± 2 mm Hg·L^-1·min^-1, SNP 22 ± 2 to 19 ± 2 mm Hg·L^-1 min^-1) and in mean pulmonary artery pressure (nitroglycerin 39 ± 1 to 35 ± 1; SNP 40 ± 1 to 36 ± 2 mm Hg). Both drugs significantly increased the PVR/SVR ratio. Hydralazine was the only drug that significantly increased cardiac output (1.6 ± 0.2 to 1.9 ± 0.3 L/min). Hydralazine had no significant effect on mean pulmonary artery pressure, reduced PVR to the smallest extent (11%), and resulted in the largest increase in the PVR/SVR ratio (from 0.52 ± 0.04 to 0.80 ± 0.08). In this model of increased pulmonary vasculature resistance prostaglandin E₁ caused an equivalent amount of pulmonary and systemic vasodilation, as expressed by the PVR/SVR ratio. Hydralize caused the least amount of pulmonary vasodilation for a given amounts of systemic vasodilation. Nitroglycerin and SNP were intermediate in their effects between prostaglandin E₁ and hydralazine.