Hypoxemia is a major problem with significant adverse effects on both the fetus and the newborn infant. The accepted experimental model for the investigation of fetal hypoxemia has been to reduce the inspired oxygen concentration in the maternal ewe. Using this model, fetal hypoxemia is frequently associated with reduced cardiac output due to reduced stroke volume and arterial hypertension. Previous investigations have demonstrated that myocardial oxygen delivery increases during fetal hypoxemia primarily by increased coronary blood flow accomplished by coronary vasodilation. A proposed mechanism for the reduction in combined ventricular output in the fetus with hypoxemia is that stroke volume drops due to an associated increase in arterial pressure. Previous investigations from this laboratory have demonstrated that the two fetal ventricles have distinctly different sensitivities to arterial pressure--that is, increases in arterial pressure result in significant reductions in right ventricular stroke volume, while left ventricular stroke volume remains constant. Hypoxemia, when associated with fetal arterial hypertension would, by itself, be expected to produce a substantial reduction in right ventricular output. The purpose of this investigation is to determine the mechanism(s) for the reduction in fetal cardiac output with hypoxemia. The plan is to test the hypotheses that: 1) stroke volume sensitivity to increased arterial pressure, or 2) inadequate coronary blood flow with hypoxemia and increased arterial pressure, reduces cardiac output. To accomplish these goals, we plan the following specific aims in the chronically Instrumented near term fetal lamb: a) generate biventricular function curves before and during fetal hypoxemia, and during hypoxemia after normalization of arterial pressure, b) generate biventricular stroke volume-arterial pressure relationship curves during hypoxemia, c) determine the arterial pressure at which myocardial blood flow limits biventricular performance during normoxemia and during hypoxemia.
These specific aims i ntegrate the principal investigator's long-term interest and commitment to the understanding of the pathophysiology of fetal and neonatal hypoxemia with a laboratory possessing expertise in fetal hemodynamics and ventricular function.
| Lohr, J L; Reller, M D; Morton, M J et al. (1994) Atrial myocardial blood flow during acute right ventricular pressure load and adenosine infusion in late gestation fetal sheep. Pediatr Res 35:325-8 |
| Reller, M D; Morton, M J; Giraud, G D et al. (1992) Maximal myocardial blood flow is enhanced by chronic hypoxemia in late gestation fetal sheep. Am J Physiol 263:H1327-9 |
| Reller, M D; Morton, M J; Giraud, G D et al. (1992) Severe right ventricular pressure loading in fetal sheep augments global myocardial blood flow to submaximal levels. Circulation 86:581-8 |
