Inhaled nitric oxide versus aerosolized iloprost for the treatment of pulmonary hypertension with left heart disease

Abstract

OBJECTIVE:: To determine the effects of inhaled nitric oxide (NO) and aerosolized iloprost on pulmonary hemodynamics and lung edema formation in a rat model of pulmonary hypertension due to congestive heart failure (CHF). DESIGN:: Prospective, randomized, controlled study. SETTING:: Research laboratory. SUBJECTS:: One hundred sixty male Sprague-Dawley rats. INTERVENTIONS:: CHF was induced by supracoronary aortic banding whereas sham-operated rats served as controls. CHF rats or controls inhaled NO, aerosolized iloprost, or 0.9% NaCl for 3 minutes each. Additional CHF groups received intravenous infusions of iloprost, sodium nitroprusside, or 0.9% NaCl. For prolonged drug administration over 150 minutes, NO was inhaled continuously whereas aerosolized iloprost was administered for 3 minutes each at 45-minute intervals. MEASUREMENTS AND MAIN RESULTS:: Dose-response relations in rats with CHF showed a maximal pulmonary-selective reduction in blood pressure at 20 ppm NO and 2.5 μg/mL aerosolized iloprost, with iloprost therapy resulting in a greater decrease in pulmonary arterial pressure (PAP). At these doses, both vasodilators decreased pulmonary vascular resistance and increased venous oxygen saturation (Svo2) in the absence of systemic hemodynamic effects. No pulmonary or systemic effects were detected in rats with CHF inhaling 0.9% NaCl or in control rats inhaling NO or iloprost. Intravenous infusion of iloprost or sodium nitroprusside not only reduced pulmonary but also systemic vascular resistance. During prolonged inhalation, NO caused a stable reduction in PAP, whereas PAP decreased even further during repetitive iloprost inhalations. After 150 minutes, iloprost-treated rats had a higher Svo2 and lesser edema as compared with animals with CHF inhaling NO or untreated rats with CHF, although differences in wet/dry weight ratio did not reach statistical significance (p < 0.06). CONCLUSIONS:: Inhaled vasodilators may offer an effective, safe, and pulmonary-selective strategy for the treatment of pulmonary hypertension in left heart disease, and inhaled iloprost may be superior to NO in this condition. © 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.