Hypoxic Pulmonary Hypertension

Abstract

Chronic exposure to hypoxia, either from residence at altitude or from a host of underlying diseases, can lead to pulmonary vascular remodeling and chronic pulmonary hypertension (PH). Hypoxic pulmonary hypertension is characterized by mild to moderate pulmonary vascular remodeling that is largely reversible as compared with the progressive irreversible disease seen in other forms of PH (i.e., idiopathic disease). The underlying mechanisms of disease involve complex inflammatory processes mediated by the interplay between the effects of pressure and hypoxia on the vascular system. Hypoxic pulmonary hypertension stems from five major causes: chronic obstructive pulmonary disease (COPD), chronic exposure to altitude, interstitial lung disease, sleep-disordered breathing, and chronic hypoventilation. Clinical manifestation of hypoxic PH can generally be categorized into two major phenotypes. Representing the majority of disease, the first phenotype is characterized by mild to moderate PH without right heart failure that is often reversible and likely represents more of an adaptation to chronic hypoxia. The second phenotype is much more rare, characterized by “out-of-proportion” severe PH resulting in right heart failure and death and likely represents more of a pathologic adaptation to hypoxia and the underlying disease. The mechanisms differentiating these two phenotypes have not been elucidated but go beyond those involving pure hypoxia. Aside from treatment of hypoxia and/or hypoventilation, there are no efficacious pharmacotherapeutics for hypoxic PH. Current efforts are aimed in finding drugs that improve hemodynamics and/or improve pulmonary vascular remodeling without detrimental effects on gas exchange.