The Paradox of Pulmonary Vascular Resistance: Restoration of Pulmonary Capillary Recruitment as a Sine Qua Non for True Therapeutic Success in Pulmonary Arterial Hypertension
David Langleben, Stylianos E. Orfanos, Benjamin D. Fox, Nathan Messas, Michele Giovinazzo, John D. Catravas
Abstract
Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension therapies that have mainly antiproliferative properties are being developed to try and diminish proliferative cellular obstruction in precapillary arterioles. If effective, those agents should restore capillary recruitment and, during exercise testing, pulmonary arterial pressure should remain low despite increasing pulmonary blood flow. The effectiveness of every novel therapy for pulmonary arterial hypertension should be evaluated not only at rest, but with measurement of exercise pulmonary hemodynamics during clinical trials.