Development of a Pre-Clinical Rodent Model of Pulmonary Arterial Hypertension

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Abstract

Pulmonary arterial hypertension (PAH) encompasses a group of rare but lethal diseases characterized by progressive narrowing and occlusion of the small pulmonary arteries, stress on the right-side of the heart and eventually death from right-heart failure. New treatments are urgently needed since current therapy does not reverse this progressive disease and 50% of patients die within 7 years of their diagnosis. In order to investigate new therapeutic targets, we have implemented a pre-clinical rodent model of PAH and incorporated serial cardiac magnetic resonance imaging in addition to traditional assessments of hemodynamics, right ventricular hypertrophy, and histopathological pulmonary vascular remodeling. PAH is induced in rats by a single subcutaneous injection of SU-5416, a vascular endothelial growth factor receptor 2 inhibitor, followed by 3 weeks of exposure to hypoxia (10% FiO2). The rats are then returned to normoxia (21% FiO2) for periods ranging between 2-11 weeks. CCM 19-03 was approved by the ACUC in June 2019 and initial experiments began in August 2019.