Models of congenital heart disease in fetal lambs.
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 less than 0.01). Within seven days, the LV/right ventricular (RV) weight ratio decreased to 70% of control (P less than 0.01), and the mean LV/RV chamber volume decreased to less than one-half of control (P less than 0.001), simulating an early form of the hypoplastic left heart syndrome. With LV outflow obstruction, mean LVO decreased to 64% of control (P less than 0.05). Mean LV/RV wall thickness doubled (P less than 0.0001) and mean LF/RV chamber volume decreased to less than one-half of control (P less than 0.0001). Within four to ten 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.
D000818:Animals; D002302:Cardiac Output; D003326:Coronary Circulation; D004195:Disease Models, Animal; D005260:Female; D005318:Fetal Heart / Q000503:physiopathology; D005323:Fetal Monitoring; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006965:Hyperplasia; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D011247:Pregnancy; D012756:Sheep