Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling.

The natural history of pulmonary vascular disease associated with congenital heart disease (CHD) depends on associated hemodynamics. Patients exposed to increased pulmonary blood flow (PBF) and pulmonary arterial pressure (PAP) develop pulmonary vascular disease more commonly than patients exposed to increased PBF alone. To investigate the effects of these differing mechanical forces on physiologic and molecular responses, we developed two models of CHD using fetal surgical techniques: ) left pulmonary artery (LPA) ligation primarily resulting in increased PBF and ) aortopulmonary shunt placement resulting in increased PBF and PAP.

Analysis of the microRNA signature driving adaptive right ventricular hypertrophy in an ovine model of congenital heart disease.

The right ventricular (RV) response to pulmonary arterial hypertension (PAH) is heterogeneous. Most patients have maladaptive changes with RV dilation and RV failure, whereas some, especially patients with PAH secondary to congenital heart disease, have an adaptive response with hypertrophy and preserved systolic function. Mechanisms for RV adaptation to PAH are unknown, despite RV function being a primary determinant of mortality.

Pushing the envelope: a treat and repair strategy for patients with advanced pulmonary hypertension associated with congenital heart disease.

Pulmonary arterial hypertension (PAH) is a frequent complication of congenital heart disease as a consequence of altered pulmonary hemodynamics with increased pulmonary blood flow and pressure. The development of pulmonary vascular disease (PVD) in this patient population is an important concern in determining operative strategy. Early, definitive surgical repair, when possible, is the best therapy to prevent and treat PVD.

Pulmonary artery smooth muscle cell hyperproliferation and metabolic shift triggered by pulmonary overcirculation.

Vascular cell hyperproliferation and metabolic reprogramming contribute to the pathophysiology of pulmonary arterial hypertension (PAH). An important cause of PAH in children with congenital heart disease (CHD) is increased pulmonary blood flow (PBF). To better characterize this disease course we studied early changes in pulmonary artery smooth muscle cell (PASMC) proliferation and metabolism using a unique ovine model of pulmonary overcirculation.

Right ventricular nitric oxide signaling in an ovine model of congenital heart disease: a preserved fetal phenotype.

We recently reported superior right ventricle (RV) performance in response to acute afterload challenge in lambs with a model of congenital heart disease with chronic left-to-right cardiac shunts. Compared with control animals, shunt lambs demonstrated increased contractility because of an enhanced Anrep effect (the slow increase in contractility following myocyte stretch). This advantageous physiological response may reflect preservation of a fetal phenotype, since the RV of shunt lambs remains exposed to increased pressure postnatally.