Propranolol uptake by dog lung: effect of pulmonary artery occlusion and shock lung

First-pass lung uptake of propranolol in catheterized ambulant dogs was measured by comparison the difference between the ratios of [14C]propranolol to indocyanine green (ICG) before and after a single passage through the pulmonary circulation. Uptake was 56 +/- 5, 53 +/- 8, and 61 +/- 10% (mean +/- SD) when 0.02, 0.2, and 2.0 mg of propranolol were injected, respectively. There was a negative though unimportant correlation between percent uptake and cardiac output. Analysis of paired propranolol and ICG outflow curves confirmed the lack of saturation with increasing dose and suggested the involvement of simple diffusion. In four dogs uptake fell from 4.76 +/- 6.8 to 40.4 +/- 8.2% (0.05 greater than P greater than 0.025) during partial occlusion of the pulmonary circulation by a Swan-Ganz catheter balloon and rose again to 51.2 +/- 6.4% after relief of the occlusion. Propranolol uptake, measured serially in five dogs with indwelling catheters, was initially 55% but fell linearly to 30% over 2 wk (r = -0.59, P less than 0.001), and necropsy showed pathological features of shock lung. A similar study performed on three dogs within 4 days of catheterization showed no change in uptake of the drug. Propranolol uptake appears to reflect both quantitative and qualitative changes in the pulmonary endothelium. This method may therefore be valuable in studying the pulmonary endothelium in health and disease.