Spatial distribution of hypoxic pulmonary vasoconstriction in the supine pig

Abstract

Hypoxic pulmonary vasoconstriction (HPV) serves to maintain optimal gas exchange by decreasing perfusion to hypoxic regions. However, global hypoxia and nonuniform HPV may result in overperfusion of poorly constricted regions leading to local edema seen in high-altitude pulmonary edema. To quantify the spatial distribution of HPV and its response to regional Po2 (Pr(O2)) among small lung regions, five pigs were anesthetized and mechanically ventilated in the supine posture. The animals were ventilated with an inspired O2 fraction (Fi(O2)) of 0.50 and 0.21 and then (in random order) 0.15, 0.12, and 0.09. Regional blood flow (Q) and alveolar ventilation (Va) were measured by using intravenous infusion of 15 microm and inhalation of 1-microm fluorescent microspheres, respectively. Pr(O2) was calculated for each piece at each Fi(O2). Lung pieces differed in their Q response to hypoxia in a manner related to their initial Va/Q with Fi(O2) = 0.21. Reducing Fi(O2) < 0.15 decreased Q to the initially high Va/Q (higher Pr(O2)) regions and forced Q into the low Va/Q (dorsal-caudal) regions. Resistance increased in most lung pieces as Pr(O2) decreased, reaching a maximum resistance when Pr(O2) is between 40 and 50 Torr. Local resistance decreased at PrO2 < 40 Torr. Pieces were statistically clustered with respect to their relative Q response pattern to each Fi(O2). Some clusters were shown to be spatially organized. We conclude that HPV is spatially heterogeneous. The heterogeneity of Q response may be related, in part, to the heterogeneity of baseline Va/Q.

Advances in magnetic resonance imaging of lung physiology

“…It has been hypothesized that hypoxic pulmonary vasoconstriction may be nonuniform in HAPE, an idea supported by the work of Hlastala et al in mammalian lungs (40). The ASL data suggest this process may be fundamentally different in HAPE-susceptible individuals, at least after they have developed HAPE on one occasion, providing insight into the inciting mechanism of the disease.…”

Effect of Altitude on the Heart and the Lungs

“…48 Magnetic resonance imaging in humans who have a normal PAP response to hypoxia has demonstrated that lung perfusion is inhomogeneous during hypoxia, 49 suggesting that HPV is normally inhomogeneous. Findings in HAPEsusceptible individuals 50 and in pigs 48 suggest that this inhomogeneity increases with the magnitude of HPV.…”

“…48 Magnetic resonance imaging in humans who have a normal PAP response to hypoxia has demonstrated that lung perfusion is inhomogeneous during hypoxia, 49 suggesting that HPV is normally inhomogeneous. Findings in HAPEsusceptible individuals 50 and in pigs 48 suggest that this inhomogeneity increases with the magnitude of HPV. Possible mechanisms that could account for inhomogeneity of HPV are baseline ventilation-perfusion ratio (V/Q) inhomogeneity with greater HPV in areas with low ventilation in relation to perfusion, 48 regional differences in endothelial release of NO, 51 and uneven distribution of smooth muscle cells in pulmonary arterioles.…”

Microsphere maps of regional blood flow and regional ventilation

“…Melsom et al (41) first demonstrated consistent region-dependent changes in blood flow in response to hypoxia in awake sheep. Hlastala et al (32,39,53) investigated the regional blood flow response to different levels of hypoxia in both anesthetized dogs and pigs. Applying the cluster analysis approach previously utilized in the temporal change study cited above, Hlastala et al were able to demonstrate relatively stereotypical regional changes in flow distribution among all animals, with specified regions receiving more blood flow during hypoxia and other regions receiving less flow.…”