PULMONARY MICROVASCULAR PERMEABILITY - RESPONSES TO HIGH VASCULAR PRESSURE AFTER INDUCTION OF PACING-INDUCED HEART-FAILURE IN DOGS

The pressure threshold for injury of pulmonary capillaries is approximate to 50 to 55 cm H2O in the canine lung, as measured by changes in the filtration coefficient (K-f,K-c). Since the pulmonary endothelial basement membrane has been observed to thicken in patients with heart failure and pulmonary venous hypertension, we hypothesized that both baseline permeability and the threshold for high-vascular-pressure injury would be altered as a result. Dogs (n=12) were chronically paced at 245 beats per minute for approximate to 4 weeks, then were paced at 225 beats per minute for an additional 3 weeks. Lung lobes from anesthetized paced dogs and additional control dogs (n=14) were then isolated, ventilated, and perfused with blood. Although vascular resistance was increased nearly threefold and vascular compliance reduced by 50% in the paced group, K-f,K-c referenced to 1 g blood-free dry weight was no different from control. Despite this lack of difference at normal pulmonary vascular pressures, several significant results were obtained. First, in the paced group there was a significant increase in the threshold for high-vascular-pressure injury: K-f,K-c measured at pulmonary vascular pressures commonly seen in heart failure (20 to 50 cm H2O) were significantly less in this group compared with control. Model predictions showed that in vivo, this difference in K-f,K-c would result in a 50% reduction in the amount of water and protein cleared across the pulmonary capillary endothelial barrier in the paced group. Next, challenge with high vascular pressure resulted in less accumulation of residual blood in this group compared with control. Finally, in separate groups of animals, morphometric analysis of the alveolocapillary barrier showed that after either 4 or 7 to 8 weeks of pacing, endothelial, interstitial, and epithelial thicknesses were increased compared with control. Together, these results suggest that vascular remodeling confers a modest but important increase in the resistance of these lungs to high-vascular-pressure injury and the development of alveolar edema.