Models of congenital heart disease in fetal lambs

Abstract

Intracardiac flow patterns were chronically altered by partially obstructing left ventricular (LV) inflow or outflow in midgestational fetal lambs. Physiological measurements of the fetal circulation were made serially through indwelling catheters and the use of radioactive microspheres. With LV inflow obstruction, mean LV output (LVO) decreased to 30% of control (P < 0.01). Within 7 days, the LV/right ventricular (RV) weight ratio decreased to 70% of control (P < 0.01), and the mean LV/RV chamber volume decreased to less than one-half of control (P < 0.001), simulating an early form of the hypoplastic left heart syndrome. With LV outflow obstruction, mean LVO decreased to 64% of control (P < 0.05). Mean LV/RV wall thickness doubled (P < 0.0001) and mean LV/RV chamber volume decreased to less than one-half of control (P < 0.0001). Within 4 to 10 days after increasing LV afterload, a large increase in LV mass occurred, which was demonstrated by morphometric analysis to be due to hyperplasia of ventricular myocytes. LV chamber volume decreased somewhat, simulating moderately severe congenital aortic stenosis. Over the long term (30-36 days), the mean LV/RV weight ratio decreased and the LV chamber was nearly obliterated, simulating very severe congenital aortic stenosis. The results suggest that by varying preload and afterload in both ventricles of the fetus, various forms of congenital heart disease may be simulated.