Analysis of the pathologic impact of site specific accumulations of extravascular pulmonary fluid

The acute respiratory distress syndrome is characterized by acute onset, bilateral infiltrates on chest x-ray and a decreased ratio of arterial oxygen content to inspired oxygen content, all in the absence of left atrial hypertension. ARDS is associated with a mortality rate of approximately 40% and occurs due to increased permeability of the pulmonary endothelium which leads to interstitial fluid accumulation. Accepted models suggest that symptoms occur as fluid which transverses the capillary endothelium collects in the alveolar air spaces thereby increasing the diffusion barrier and inactivating surfactant. This perspective does not consider findings of segment specific permeability changes along the arterial-capillary-venous axis. Despite the fact that at baseline and in many models of acute lung injury the conduit vessels are responsible for the greatest share of trans-endothelial fluid movement the potential role of increased permeability of extra-capillary vessels and resulting perivascular fluid accumulations in the pathophysiology of ARDS has not been addressed. In the current work we show that segment specific increases in endothelial permeability occur based on phenotypic differences in endothelial cell populations that lead to site-specific fluid accumulations. We show that when permeability is moderately, equally increased in capillaries and extra-capillary vessels, that compliance is decreased only in those lungs with perivascular cuffs resulting from increased large vessel permeability. We show that perivascular cuffs decrease dynamic compliance, static compliance and hysteresis due to increases in tissue damping and tissue elastance. Thus, segment specific increases in vascular permeability lead to pathophysiologic consequences. Specifically, an increase in large vessels permeability impairs pulmonary mechanics.