I propose to study the developmental changes in myocardial contractility and inotropic reserve from the newborn period through the first month after birth in the chronically-instrumented lamb. Many studies have demonstrated high resting indices of ventricular performance in the newborn, but specific assessment of contractility has not been investigated. It will continue with the work that I have begun on the normal newborn, and will expand this work to include models of several forms of congenital heart disease: 1) chronic hypoxemia secondary to a right-to-left atrial shunt and right ventricular outflow tract obstruction; 2) left ventricular hypertrophy (produced in utero) secondary to LV outflow tract obstruction both with low and normal/high coronary artery perfusion pressure; and 3) LV volume overload secondary to a left-to-right shunt at the ductus arteriosus. To assess contractility, lambs will be operated upon within 3 days of birth. Via a left thoracotomy, catheters are placed in the ascending aorta, superior venna cava, pulmonary artery, and left atrium; a pressure-tip catheter in the apex of the LV; an echo transducer sutured to the LV epicardium to record LV wall thickness and minor axis dimension; and a flow transducer placed around the pulmonary artery. Following a greater than and equal 3 day recovery period, studies will be performed twice weekly to assess contractility at rest, and weekly under maximal Beta-adrenergic stimulation with isoproterenol and Beta-adrenergic blockade with propranolol. Each study consists of measuring LV pressure, dimension and wall thickness at 20 different levels of afterload during a graded phenylephrine infusion with vagal blockade using atropine to maintain a constant heart rate. At each afterload, """"""""end-systolic"""""""" wall stress (WSt) and the cube of LV diameter (LVVI) are calculated. The slope of the WSt-LVVI relationship is the index of contractility used. With this information, I will be able to define myocardial contractility, its development and reserve, over the first month of life in normal lambs and those with simulated congenital heart disease. Since inotropic agents are a mainstay in the treatment of heart disease in the newborn, it is important to have this information in order to outline a more rational approach to their use in neonatal heart disease.
| Teitel, D F; Sidi, D; Chin, T et al. (1985) Developmental changes in myocardial contractile reserve in the lamb. Pediatr Res 19:948-55 |
| Teitel, D; Sidi, D; Bernstein, D et al. (1985) Chronic hypoxemia in the newborn lamb: cardiovascular, hematopoietic, and growth adaptations. Pediatr Res 19:1004-10 |
