Pathophysiology of Acute Respiratory Distress Syndrome and COVID-19 Lung Injury.

The pathophysiology of acute respiratory distress syndrome (ARDS) is marked by inflammation-mediated disruptions in alveolar-capillary permeability, edema formation, reduced alveolar clearance and collapse/derecruitment, reduced compliance, increased pulmonary vascular resistance, and resulting gas exchange abnormalities due to shunting and ventilation-perfusion mismatch. Mechanical ventilation, especially in the setting of regional disease heterogeneity, can propagate ventilator-associated injury patterns including barotrauma/volutrauma and atelectrauma. Lung injury due to the novel coronavirus SARS-CoV-2 resembles other causes of ARDS, though its initial clinical characteristics may include more profound hypoxemia and loss of dyspnea perception with less radiologically-evident lung injury, a pattern not described previously in ARDS.

Rapid Ascent to 4559 m Is Associated with Increased Plasma Components of the Vascular Endothelial Glycocalyx and May Be Associated with Acute Mountain Sickness.

Background: The stress of high altitude alters vascular permeability, which may be related to structural changes in the endothelial glycocalyx. We aimed to study these changes by measuring plasma concentrations of several glycocalyx components upon exposure to high altitude. Methods: Plasma collected from 17 subjects at low altitude (423 m) and at three time points (7, 20, and 44 hours) after rapid ascent to high altitude (4559 m) were evaluated for concentrations of three glycocalyx components: syndecan-1, intercellular adhesion molecule-1 (ICAM-1), and heparan sulfate. Vital signs and echocardiographic measurement of systolic pulmonary artery pressure (sPAP) and cardiac output were also obtained at low and high altitudes. Results: Mean age of the study population was 35.5 ± 11.2 years with a body mass index of 22.7 ± 2.5 kg/m2. Concentrations of ICAM-1 and heparan sulfate increased from baseline to 7 hours after arrival at high altitude; the ICAM-1 rise persisted at 20 hours. Syndecan-1 concentrations were increased only at 44 hours. Increased ICAM-1 concentrations correlated with sPAP and peripheral edema. Elevations in heparan sulfate appeared to correlate with acute mountain sickness (AMS). Conclusions: Levels of circulating glycocalyx components increase after exposure to high altitude and may correlate with AMS. Measuring plasma concentrations of various glycocalyx components could serve as a useful tool for further evaluation of vascular endothelial injury and repair in illness at high altitude.