Aerosolized Vasodilators in Pulmonary Hypertension

Abstract

Pulmonary hypertension is a life-threatening disease characterized by an increase in artery pressure and vascular resistance in the pulmonary circulation. A primary form of pulmonary hypertension with unknown causes is to be distinguished from the far more frequent secondary forms based on known pulmonary and extrapulmonary disorders. An imbalance in the synthesis of vasoconstrictive and vasodilative agents seems to play an important role in the etiology of pulmonary hypertension. This pathophysiological background offers the possibility to develop treatment strategies, including application of vasodilative drugs. The intravenous administration of vasodilative agents, however, lacks pulmonary selectivity leading to systemic side effects. Therefore, the application of aerosol techniques for alveolar deposition of vasodilatory drugs was proposed and several studies with inhaled iloprost, a stable prostacyclin analogue, demonstrated preferential vasorelaxation in the pulmonary circulation, with the maximum pulmonary vasodilatory potency corresponding to that of intravenous prostacyclin. Clinical experiences with long-term inhaled iloprost are available showing sustained effects on exercise capacity and pulmonary hemodynamics in patients with pulmonary hypertension. Due to the necessary frequent inhalations (up to 12 times a day) and the potency of the prostaglandins, the choice of the nebulizer is critical, requiring physical characterization and device comparison studies under the right heart-catheter conditions. The concept of aerosolized vasodilators is meanwhile well established and offers a promising perspective in the treatment of pulmonary hypertension.