The Vascular Site of Action of Hypoxia in the Neonatal Pig Lung

Abstract

ABSTRAm. To determine the vascular site(s) of action of hypoxia in the neonatal pig, isolated lungs were perfused at a constant flow rate and left atrial pressure; arterial, venous, and double occlusions were performed. The distribution of the total pulmonary vascular resistance and the total dynamic vascular compliance were calculated using a model of the pulmonary circulation consisting of upstream, central, and downstream compliances and resistances upstream and downstream of central compliance. In addition, the static vascular compliance was measured by venous followed by arterial occlusion, and the total vascular volume was measured by dyedilution. In this preparation during control conditions alveolar Po2 = 12 + 2 kPa), total pulmonary vascular resistance was nearly evenly divided between resistance upstream and downstream of double occlusion pressure and total dynamic vascular compliance was concentrated mainly in the central compliance (7% upstream compliance, 8290 central compliance, and 11 % downstream compliance). Hypoxia (alveolar Po2 = 4 + 1 kPa) increased both resistance upstream of double occlusion pressure ( p < 0.005) and resistance downstream of double occlusion pressure ( p < 0.02) and decreased central compliance (p < 0.005). Hypoxia also decreased total pulmonary blood volume ( p < 0.02). These results suggest that in the pulmonary vasculature of the neonatal pig, hypoxia results mainly in I) arterial constriction as evidenced by a large increase in upstream resistance and a decrease in total pulmonary blood volume and 2) a smaller but significant venous constriction. This venous constriction may have implications in the pathogenesis and therapy of pulmonary vascular diseases associated with hypoxia such as postasphyxial lung disease and bronchopulmonary dysplasia. (Pediarr Res 35: 25-29, 1994 The neonate is at a high risk for pulmonary vascular diseases that manifest increased pulmonary vascular resistance such as persistent pulmonary hypertension of the newborn, bronchopulmonary dysplasia, and certain forms of congenital heart disease (1). The neonatal pig has been used extensively as a model for pulmonary vascular development and disease (2-14) because the postnatal morphometric pulmonary development closely parallels the human but on a more compact time scale (14). Typically, pulmonary arterial pressure and flow have been measured during conditions that mimic certain aspects of pulmonary vascular disease (3-14), such as alveolar hypoxia. The pressure and flow data alone provide an incomplete picture of the pulmonary vascular response. For example, the arterial and/or venous site of action may be important in determining the impact on cardiopulmonary function. In the adult, it has been shown that hypoxia causes arterial constriction (1 5-2 1 ), which implies a risk for right ventricular failure, but not necessarily for pulmonary edema because capillary pressure would not be affected. On the other hand, in the neonatal pig (2) and lamb (22) there is some evidence that the pulmonary veins m...

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

“…This is consistent with our previous studies in isolated perfused neonatal pig lungs (18,37). Furthermore, in isolated perfused lamb lungs, NOS inhibition increased basal perfusion pressure (21).…”

Hypoxic Pulmonary Vasoconstriction

“…In isolated ferret lungs perfused at different flows and constant P LA , hypoxia increased P PA -P do markedly and P do -P LA slightly, and did not alter vascular compliance, indicating that HPV occurred mainly in the arterial region (225). Similar results were obtained in lungs of neonatal pigs (1369). These results are not necessarily inconsistent with inflow/outflow occlusion data discussed above, which suggested that HPV occurred predominantly in the middle compliant region (637,712,714,1648,1914).…”

Meconium aspiration induces a concentration-dependent pulmonary hypertensive response in newborn piglets

“…In fact, similar to our results, hypoxia is known to increase both the precapillary and postcapillary resistances in the lungs of newborn pigs. 21 On the other hand, it has been proposed that the developing pulmonary hypertension is caused by vascular structural changes from prenatal chronic stress rather than by the aspirated meconium.…”