Lung inflation and alveolar permeability to non-electrolytes in the adult sheep in vivo.

1. Experiments were performed on adult sheep to determine the effect of lung distension on the passive permeability of alveoli to water soluble non-electrolytes. With the animal breathing oxygen spontaneously, a segment of one lung was isolated by passing a balloon-tipped catheter through a tracheostomy into a distal bronchus. This isolated atelectatic segment was filled with an isosomotic saline solution containing radio-labelled solutes of known molecular size: [125I]albumin, [14C]inulin, [14C]-sucrose, [3H]mannitol, and [14C]urea. The segment was inflated with oxygen either to a preselected pressure, or to a predetermined fraction of its capacity. Inflation was then maintained for several 10-15 min periods between which the oxygen supply was disconnected and the saline sampled, allowing the tracer concentrations to be measured. 2. At low inflating pressures (20-32 cmH2O) and at low volumes (24-54% of capacity), alveolar permeability to water soluble solutes was slight and could be characterized in terms of a membrane penetrated by cylindrical water filled pores of 0-5-1-6 nm radius. In all experiments showing restricted diffusion, absorption of saline occurred. 3. There was a positive correlation between the degree of lung inflation and pore radius in both the pressure controlled and volume controlled experiments. At high inflating pressures and at inflation volumes which were close to the total capacity of the isolated segment, restriction of solute diffusion was lost; in five out of six such experiments there was a net movement of liquid into the alveoli. 4. These results can be explained by postulating that as the lung epithelium is progressively stretched there is an opening up of water filled channels between alveolar cells. At peak inflation, restriction of diffusion of water soluble solutes is lost, and the alveolar epithelium ceases to function as a barrier between the circulation and air spaces.