Interindividual Differences in the Adaptive Response of the Lung to Hypoxia

The adaptive response of the lung to hypoxia is dominated by the risk of potential development of lung edema on one side, and, on the other, by the need to develop an adaptive response allowing to preserve the oxygen diffusion-transport function. The edemagenic condition relates to the increased cardiac output and microvascular permeability. The rigidity of the extravascular interstitial matrix represents the main mechanism to resist edema formation: due to this peculiar feature, the increase in microvascular filtration leads to a corresponding remarkable increase in interstitial pressure that strongly buffers filtration. A further antiedemagenic mechanism is based on blood flow restriction to the septal microcirculation. This occurs by active vasoconstriction in the regions where edema tends to develop. A further cause of blood flow limitation in the septal capillary bed is due to the increase in the interstitial pressure that decreases the patency of the capillaries. The blood flow limitation in the septal capillary bed leads to increased perfusion of the corner vessels running at the edge of the alveoli; the overall increase in blood flow vascular resistance is matched by an increase in pulmonary artery pressure. A surprising finding is that in about 55% of subjects, DL _CO increased in hypoxia (exposure to 3500 m), reflecting an increase in conductance of the air blood barrier Dm that largely overruled the decrease in in capillary blood volume (Vc). In about 25% subjects DL _CO remained unchanged in hypoxia while it decreased in 15%. We will explore how individual oxygen diffusion-transport features influence this response.