The long range objective is to define maturational changes in the pulmonary microcirculation. The specific areas to be studied in this proposal are: maturational changes in (a) the longitudinal distribution of pulmonary vascular pressures; (b) vasomotor control of the pulmonary microcirculation; and (c) the influence of mechanical factors on the pulmonary microcirculation. Another area of study will be to define the effect of chronic hypoxia on the maturation of the mechanical properties and vasomotor control of the pulmonary microcirculation. The rationale is that the first group of studies will explain why the tendency towards fluid accumulation is greater in newborn than in mature lungs and why newborns are more susceptible than adults to develop pulmonary edema under specific circumstances (hypoxia, lung inflation, increased pulmonary blood flow). The other studies will show how the regulation of lung fluid balance is disrupted in neonatal cardiopulmonary disorders that are characterized by chronic hypoxia. To define maturational changes in the pulmonary microcirculation, the direct micropuncture technique will be used to measure microvascular pressures in isolated, perfused lungs of newborn and adult animals. The pressure drops across each vascular segment will be measured under control and the following experimental conditions: after alteration of blood flow, removal of vasomotor tone, exposure to hypoxia, infusion of 5 hydroxytryptamine, and at different levels of lung inflation and left atrial pressure. In a separate series of studies, microvascular pressures will be measured in isolated lungs of newborn pigs that have been exposed to an hypoxic environment for 2-7 days. For these studies, microvascular pressures will be measured under control conditions and then after alteration of blood flow or during exposure to hypoxia. Finally, to ensure that microvascular pressures are the same in isolated lungs as they are in lungs of living newborns, microvascular pressures will also be measured in lungs of anesthetized newborn lambs. The results of these studies should help define the changes that take place during postnatal lung development, improve our under- standing of the pathophysiology of newborn cardiopulmonary disorders, and lead to improvements in the care of critically ill newborns.
