Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation

Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation. J Appl Physiol 102: 794-802, 2007. First published September 21, 2006; doi:10.1152/japplphysiol.00742.2006. Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing Tc-99m-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs. Microvascular permeability was simultaneously estimated measuring the accumulation of In-111-transferrin in lungs. Four levels of lung distension (corresponding to 15, 20, 25, and 30 cmH(2)O end-inspiratory airway pressure) were studied during mechanical ventilation. Computed tomography scans showed that the zone of alveolar flooding underwent the same distension as the contralateral lung during inflation with gas. Increasing lung tissue stretch by ventilation at high airway pressure immediately increased microvascular, but also alveolar epithelial, permeability to proteins. The same end-inspiratory pressure threshold (between 20 and 25 cmH2O) was observed for epithelial and endothelial permeability changes, which corresponded to a tidal volume between 13.7 +/- 4.69 and 22.2 +/- 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar space (In-111-transferrin lung-to-heart ratio slope) was constant over 120 min, the rate at which Tc-99m-albumin left air spaces decreased with time. This pattern can be explained by changes in alveolar permeability with time or by a compartment model including an intermediate interstitial space.