Animal models of pulmonary arterial hypertension

Introduction Pulmonary arterial hypertension (PAH) is a rare syndrome of fatigue and dyspnoea, caused by increased pulmonary vascular resistance and right heart failure without an identifiable pulmonary or cardiac cause. Despite important recent advances in treatment the condition remains incurable. Background Experimental animal models of PAH rely on hypoxic or monocrotaline injected rodents, the creation of left to right shunts in lambs or piglets, ligation of the ductus arteriosus in newborn lambs, genetically manipulated rodents and tissue culture. Hypoxic pulmonary hypertension is usually only moderate and limited to medial hypertrophy with varying degrees of adventitial change, but may progress to extensive remodelling in some species. Monocrotaline induced pulmonary hypertension is severe with prominent medial hypertrophy, inflammatory adventitial remodelling and, initially, pulmonary oedema and endothelial apoptosis. Pulmonary hypertension induced by shunting remains the most realistic model of PAH but causes only moderate increase in vascular resistance due to medial hypertrophy. Pulmonary hypertension of the newborn is severe but largely vasospastic, with predominant medial hypertrophy. An increasing number of genetically manipulated rodents are becoming available for the investigation of specific signalling pathways. Viewpoint While none of the models has yet reproduced PAH each allows investigation of a specific hypothesis. Recent progress has resulted from genetic manipulation and molecular and cellular approaches. Conclusions Animal models of PAH share basic biological abnormalities which, together with the study of lung tissue from patients with severe disease should lead to better understanding of the pathology and therapeutic innovation.