Nitroglycerin therapy in the management of pulmonary hypertensive disorders

Abstract

Vasodilator therapy has not been effective in patients with pulmonary hypertension because most of the drugs that have been utilized in treating this disorder do not exert selective effects on the pulmonary circulation. Nonselective agents may cause predominant systemic vasodilation and lead to severe hypotension; they may elicit reflex activation of the sympathetic nervous system and further elevate pulmonary artery pressures; or they may exert depressant effects on right ventricular function and aggravate right-sided heart failure. Nitroglycerin has theoretic appeal as a vasodilator drug in patients with pulmonary hypertension because it exerts a direct effect on the pulmonary circulation in doses that do not affect systemic resistance vessels or the myocardium and do not activate neurohumoral reflexes. Furthermore, the drug uniquely reduces pulmonary artery pressures in addition to pulmonary vascular resistance due to its ability to dilate venous capacitance vessels. Preliminary studies with sublingual and intravenous nitroglycerin in patients with pulmonary hypertension have shown that the drug produces marked hemodynamic improvement and that clinical benefits follow long-term therapy with transcutaneous or oral nitrates. However, treatment may provoke hypotensive events in some patients and systemic hypoxemia in others; still others may fail to benefit because the pulmonary vasculature is unresponsive to any vasodilator stimulus. Further work is needed to define the benefits and risks of nitroglycerin therapy in patients with pulmonary hypertension.