Role of Endothelin-1 Receptor Antagonist in Reducing Perioperative Pulmonary Arterial Hypertension after Surgical Correction of Ventricular Septal Defect

Abstract

Introduction:In patients with systemic-to-pulmonary shunts, the type and size of the defect as well as the magnitude of the shunt are risk factors for the development of pulmonary artery hypertension (PAH). 1 Shear stress due to increased pulmonary blood flow and/ or increased pulmonary artery pressure appears to play a major role in the development of pulmonary vascular disease (PVR) related to congenital heart disease (CHD). 2 Elevated pulmonary artery pressure in ventricular septal defect (VSD) is caused by pulmonary over circulation, pulmonary vasoconstriction and pulmonary vascular disease either alone or in combination. 3 PAH in pediatric patients with VSD remains one of the most important determinant of perioperative morbidity and mortality. 4 Outcomes are significantly worse in patients with perioperative PAH and right ventricular (RV) failure prompting interest in the utility of newer therapies for this situation, including PAH-specific therapies. 5,6 While early surgical correction can prevent development of PAH in CHD, PAH has become one of the leading but unresolved medical conditions that, like primary myocardial failure, significantly increases mortality and morbidity due to perioperative pulmonary hypertensive crisis. 7,8 Endothelin-1, one of the most potent vasoconstrictors identified to date has been implicated in the pathophysiology of PAH. Endothelin-1 expression, production, and concentration in plasma and lung tissue are elevated in PAH patients and inversely correlated with prognosis. 7 Endothelin contribute to PAH pathophysiology by promoting pulmonary smooth muscle cell hypertrophy, proliferation, and vasoconstriction through their interaction with endothelin receptor ( ETRs). 9 Ambrisentan is a propanoic Acid-based endothelin receptor 1A-selective antagonist approved to once daily