Pulmonary vascular resistance (PVR) normally decreases during the month after birth and increases abruptly when hypoxia occurs. These physiological changes help to match ventilation and perfusion in the lungs and thereby facilitate respiratory gas exchange. Chronic lung injury after premature birth, sometimes called bronchopulmonary dysplasia (BPD), may be associated with abnormal development of the pulmonary circulation, with persistent elevation of PVR and a diminished vasoconstrictor response to hypoxia. To test this hypothesis, we determined PVR from measurements of pulmonary arterial and left atrial pressures and pulmonary blood flow before and during steady-state hypoxia (baseline FiO2 0.44 ± 0.04; PaO2 81 ± 3 mmHg; hypoxia FiO2 0.19 ± 0.01; PaO2 36 ± 1 mmHg) in 10 chronically catheterized lambs that were delivered operatively at 124± 1 d gestation (term = 147d) and mechanically ventilated for 3-4 wks postnatally. All lambs received surfactant (Infasurf, 350 mg) at birth and had surgery for ductus arteriosus ligation and catheter placement to allow weekly determinations of PVR. During development of chronic lung injury, documented by serial chest radiographs, pulmonary function abnormalities, and postmortem evidence of lung edema, non-uniform inflation, abnormal alveolarization and disordered elastin deposition, baseline PVR did not change significantly from the first to the last week of study. In 5 studies that were done at the end of wk 1, PVR increased by 67 ± 20% during hypoxia, whereas PVR did not change significantly with hypoxia in 8 studies that were done at the end of wk 2 and 10 studies that were done at the end of wk 3. Thus, chronic lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in PVR and results in a diminished vasoconstrictor response to hypoxia. These abnormalities of pulmonary vascular tone and reactivity may contribute to the abnormal respiratory gas exchange that often exists in infants with BPD.
