To clarify the role of charge in protein movement across the pulmonary endothelial barrier, we simultaneously measured the permeability-surface area product (PS) for native [isoelectric point (pI) 4.4-5.1] and cationic (pI 7.2-8.0) albumin in isolated rabbit lungs perfused with and without protamine sulfate. We focused our measurement on the initial (endothelial) barrier by using a technique that is based on the very rapid (3 min) uptake of tracer. This allowed us to distinguish the charge properties of the endothelium separate from other barriers. In control studies, PS was greater for cationic than for native albumin (8.67 ± 0.93 vs. 2.55 ± 0.20 x 10-2 ml · min-1 · g dry lung-1). In the presence of 1 mg/ml protamine sulfate, cationic albumin permeability was not different from control (7.34 ± 0.49 x 10-2 ml · min-1 · g dry lung-1), whereas PS for anionic albumin increased to 8.82 ± 1.32 x 10-2 ml · min-1 · g dry lung-1. Thus the protamine sulfate eliminated the difference between native and cationic albumin PS. This selective increase in anionic albumin permeability is presumably due to the cation, protamine sulfate, binding to the anionic charges on the endothelium and reducing the anionic charge-charge repulsion. If protamine sulfate had produced a general endothelial injury, the PS for both albumins would have increased. Our results suggest that the normal pulmonary endothelium is an anionic charge barrier restricting the transcapillary movement of negatively charged molecules.

The effect of papaverine on the albumin permeability-surface area product (PS), reflection coefficient (σ), and capillary filtration coefficient (K(f)) was examined in isolated rabbit lungs. Because PS and K(f) are functions of vascular surface area and permeability, we also compared papaverine with two other means of maximizing lung surface area: isoproterenol (1 x 10-7 M) and a mild increase in vascular pressure. Only lungs perfused with 0.1 mg/ml papaverine were significantly different from control. PS increased from control (2.80 ± 0.16 to 5.53 ± 0.20 ml · min-1 · g dry lung-1 x 10-2), whereas σ decreased from control (0.92 ± 0.01 to 0.78 ± 0.03). K(f) after papaverine was significantly lower than baseline predrug K(f) (5.60 ± 0.78 to 4.56 ± 0.53 ml · s-1 · cmH2O-1 · g dry lung-1 x 10-3). However, this group's predrug K(f) was higher than that of any other group. Our results indicate that papaverine increases albumin permeability and decreases endothelial selectivity. The isolated perfused lung appears fully recruited, because K(f) and PS did not increase with isoproterenol or increased vascular pressure. Papaverine should be used with caution in the Ringer-perfused lung.