Alveolar Epithelial Clearance Research Articles

Inhibition of beta-adrenergic-dependent alveolar epithelial clearance by oxidant mechanisms after hemorrhagic shock.

Endogenous release of catecholamines is an important mechanism that can prevent alveolar flooding after brief but severe hemorrhagic shock. The objective of this study was to determine whether this catecholamine-dependent mechanism upregulates alveolar liquid clearance after prolonged hemorrhagic shock. Rats were hemorrhaged to a mean arterial pressure of 30-35 mmHg for 60 min and then resuscitated with a 4% albumin solution. Alveolar liquid clearance was measured 5 h later as the concentration of protein in the distal air spaces over 1 h after instillation of a 5% albumin solution into one lung. There was no upregulation of alveolar liquid clearance after prolonged hemorrhagic shock and fluid resuscitation despite a significant increase in plasma epinephrine levels. The intravenous or intra-alveolar administration of exogenous catecholamines did not upregulate alveolar liquid clearance. In contrast, catecholamine-mediated upregulation of alveolar liquid clearance was restored either by depletion of neutrophils with vinblastine, by the normalization of the concentration of reduced glutathione in the alveolar epithelial lining fluid by N-acetylcysteine, or by the inhibition of the conversion from xanthine dehydrogenase to xanthine oxidase. These experiments provide the first in vivo evidence that a neutrophil-dependent oxidant injury to the alveolar epithelium prevents the upregulation of alveolar fluid clearance by catecholamines in the absence of a major alteration in paracellular permeability to protein after prolonged hemorrhagic shock.

Physiology and morphology of pulmonary microvascular injury with shock and reinfusion.

The effect of hemorrhagic shock and reinfusion of the shed blood on lung microvasculature was studied in 10 anesthetized dogs during a control, a shock (40-50 mmHg aortic pressure), and a reinfusion period. Pulmonary capillary hydrostatic and oncotic pressures decreased, whereas lung lymph flow and lymph-to-plasma albumin and globulin ratios increased with shock and with reinfusion, indicating an increased microvascular permeability. Calculated pore radius increased with reinfusion (p less than 0.05), whereas pore number increased both with shock and with reinfusion in eight dogs. Comparison of the autopsy results of these experiments with those of previous control and shock animals showed that with reinfusion there was a rise in lung wet-to-dry weight ratios and increased granulocytes by light microscopy. By electron microscopy, the granulocytes were intravascular, and there was alveolar wall edema without endothelial or epithelial damage. We conclude that the morphological changes in the lung with reinfusion are minimal and that our data are consistent with the hypothesis that granulocytes may cause the observed microvascular injury and interstitial edema.