Pulmonary hemodynamic effects of lung inflation and graded hypoxia in conscious sheep

To determine the separate pulmonary hemodynamic effects of lung inflation and graded hypoxia, we measured pulmonary arterial pressure (Ppa), pulmonary arterial wedge pressure, pulmonary blood flow, pleural pressure (Ppl), and alveolar oxygen tension (PAO₂) in unsedated, spontaneously breathing sheep. These measurements were obtained during room air breathing, and sequentially while the sheep breathed mixtures of oxygen balance nitrogen with oxygen concentrations of 16.7%, 13.4%, 9.3%, 13.4%, and 16.7% for 15 min each, followed by room air breathing. There was an inverse relationship between mean Ppa and PAO₂. Pulmonary vascular resistance (PVR) showed an early maximal increase with progressive hypoxia and remained above base line at the lowest PAO₂. Mean PVR for a given inspired oxygen concentration tended to be greater during progressive hypoxia than during gradual return to normoxia. On a subsequent day, the animals breathed room air, 16.7% and 9.3% oxygen balance nitrogen at functional residual capacity (mean transpulmonary pressure 4.7 cmH₂O) and at an increased lung volume (mean transpulmonary pressure 9.0 cmH₂O) produced by constant positive airway pressure. Lung inflation resulted in upward displacement of the curves of Ppa - Ppl versus PAO₂. We conclude that 1) during brief exposures to progressive hypoxia and gradual return to normoxia, the pulmonary vascular response tends to show hysteresis and 2) the combined effects of lung inflation and hypoxia on Ppa - Ppl and PVR are additive for moderate increases in Ptp.