Abstract
Hypercapnic acidosis (HCA) has beneficial effects in experimental models of lung injury by attenuating inflammation and decreasing pulmonary edema. However, HCA increases pulmonary vascular pressure that will increase fluid filtration and worsen edema development. To reconcile these disparate effects, we tested the hypothesis that HCA inhibits endothelial mechanotransduction and protects against pressure-dependent increases in the whole lung filtration coefficient (K(f)). Isolated perfused rat lung preparation was used to measure whole lung filtration coefficient (K(f)) at two levels of left atrial pressure (P(LA) = 7.5 versus 15 cm H(2)O) and at low tidal volume (LV(t)) versus standard tidal volume (STV(t)) ventilation. The ratio of K(f2)/K(f1) was used as the index of whole lung permeability. Double occlusion pressure, pulmonary artery pressure, pulmonary capillary pressures, and zonal characteristics (ZC) were measured to assess effects of HCA on hemodynamics and their relationship to K(f2)/K(f1). An increase in P(LA2) from 7.5 to 15 cm H(2)O resulted in a 4.9-fold increase in K(f2)/K(f1) during LV(t) and a 4.8-fold increase during STV(t). During LV(t), HCA reduced K(f2)/K(f1) by 2.7-fold and reduced STV(t) K(f2)/K(f1) by 5.2-fold. Analysis of pulmonary hemodynamics revealed no significant differences in filtration forces in response to HCA. HCA interferes with lung vascular mechanotransduction and prevents pressure-dependent increases in whole lung filtration coefficient. These results contribute to a further understanding of the lung protective effects of HCA.