Hypoxia has been shown to cause an increased number of pulmonary capillaries to be perfused. Changes in cardiac output and left atrial pressure have been previously ruled out as causes of this capillary recruitment. Increased pulmonary vein pressure and increased pulmonary artery pressure remain as two potential mechanisms. To differentiate between these two possible causes, we measured pulmonary artery and vein pressures with directly placed catheters and capillary recruitment with in vivo microscopy. During isocapnic hypoxia pulmonary artery pressure doubled, observed capillary recruitment increased fivefold, and pulmonary vein pressure remained constant. When the vasodilator prostaglandin E1 was infused during hypoxia, pulmonary artery pressure and capillary recruitment fell to control values and pulmonary vein pressure remained constant. Since capillary recruitment correlated with pulmonary artery pressure in each dog, but not with pulmonary vein pressure, we conclude that arterial, not venous, constriction is the probable cause of this recruitment.

To study the effect of hypoxia on the pulmonary capillaries, windows were inserted in the chest wall of 9 pentobarbital-anesthetized dogs. A microscope with an image-superimposing device was used to make drawings of the perfused capillaries. Summed lengths of individual perfused capillaries in the drawing were determined with a map-measuring tool. Total capillary length was constant between PaO2 of 160 and 70 Torr. As PaO2 fell below 70 Torr, recruitment of previously unperfused capillaries occurred in every case; at PaO2 of 40 Torr, the total length of perfused capillaries was about 4 times greater than during normoxia. There was no correlation between the recruitment of capillaries and alterations in left atrial pressure, only a weak correlation with cardiac output changes, but a very strong correlation with increased pulmonary artery pressure. This implies that recruitment was probably caused by vasoconstriction within the lung.

A fast-response O2 analyzer that samples air at low flow rates allows the quasi-instantaneous measurement of O2 concentration change in the airways of isolated blood-perfused rat lungs. This instrument and an oximeter were used to measure the stimulus-response delay time of hypoxic pulmonary vasoconstriction when the lungs were challenged with 10, 5, or 3% O2. The estimate for the shortest delay time between accomplished fall in airway O2 concentration and the onset of hypoxia-induced vasoconstriction was approximately 7 s. We found that the slope of pressure rise, but not the stimulus-response delay time, correlated with the magnitude of hypoxic vasoconstriction. Oscillations in pulmonary arterial pressure were observed when the lungs were challenged with 10% O2 but not when the challenge was 12, 5, or 3%, indicating perhaps that these oscillations were a threshold phenomenon. Established hypoxic vasoconstriction was sensitive to brief changes in airway O2 concentration. Vasodilation occurred when the gas mixture was switched from 3 to 21% O2 for two to five breaths, and vasoconstriction occurred when the gas was changed during a single breath from 5 to 3% O2.

Species with collateral ventilation have an auxiliary respiratory mechanism that could protect them, under certain circumstances, from regional alveolar hypoxia. Species without collateral ventilation may have a greater potential for routinely experiencing regional hypoxia; to maintain ventilation-perfusion balance they would have to rely on pulmonary vasoconstriction. We tested these ideas by ventilating a sublobar region of pig lung (no collateral ventilation) with 13% O2 while the rest of the lung was ventilated with 30% O2. Blood flow, as measured by radioactive microsphere distribution to the sublobar region, was reduced 50% during hypoxia. The hypoxia-induced vasoconstriction effectively defended arterial PO2. When a vasodilator was infused, regional blood flow increased to control levels; shunt fraction rose, and arterial PO2 fell. In dogs (collateral ventilation present) the same experimental maneuvers had no significant effect on regional end-tidal gases or on microsphere distribution, indicating that collateral ventilation was able to maintain ventilation-perfusion balance. When regional hypoxia was created in dogs by overcoming collateral ventilation with slightly positive airway pressure in the sublobar region, the dog acted like the pig and used hypoxic vasoconstriction to shift approximately 30% of the blood flow away from the hypoxic alveoli.

Increasing the total surface area of the pulmonary blood-gas interface by capillary recruitment is an important factor in maintaining adequate oxygenation when metabolic demands increase. Capillaries are known to be recruited during conditions that raise pulmonary blood flow and pressure. To determine whether pulmonary arterioles and venules are part of the recruitment process, we made in vivo microscopic observations of the subpleural microcirculation (all vessels less than 100 microns) in the upper lung where blood flow is low (zone 2). To evoke recruitment, pulmonary arterial pressure was elevated either by an intravascular fluid load or by airway hypoxia. Of 209 arteriolar segments compared during low and high pulmonary arterial pressures, none recruited or derecruited. Elevated arterial pressure, however, did increase the number of perfused capillary segments by 96% with hypoxia and 165% with fluid load. Recruitment was essentially absent in venules (4 cases of recruitment in 289 segments as pressure was raised). These data support the concept that recruitment in the pulmonary circulation is exclusively a capillary event.