RT Journal Article SR Electronic T1 Use of an isolated in situ canine lung perfusion model to evaluate dopamine clearance by the lung. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1271 OP 1276 VO 259 IS 3 A1 P F Cardoso A1 M Spino A1 E Mayer A1 S Q Shi A1 R D Pop A1 J Puskas A1 D Perrier A1 J Tong A1 A D Baines A1 G A Patterson YR 1991 UL http://jpet.aspetjournals.org/content/259/3/1271.abstract AB An isolated in situ lung perfusion model was used to assess dopamine clearance by the lungs in 12 dogs. The preparation consisted of a closed perfusion system in situ, in which systemic arterial blood supply was interrupted. Blood flow to the lungs was maintained at presurgery flow rates. The inflow was restricted to the lungs by the pulmonary arteries and outflow was limited to the pulmonary veins. Pulmonary artery pressure, temperature and pO2 were maintained at physiological levels. After confirmation of a stable base line, one of 3 doses (1, 2, or 5 micrograms/kg/min) of dopamine was infused over 30 min to achieve steady-state blood concentrations, then blood samples were drawn at specified times during and after the infusion. Dopamine plasma concentrations were analyzed by high performance liquid chromatography with electrochemical detection. Dose-dependent disposition of dopamine was observed in both plasma concentration-time profiles and in clearance (20.3 +/- 9.6 ml/min/kg at 5 micrograms/kg/min vs. 41.6 +/- 19.1 ml/min/kg at 1 micrograms/kg/min, P = 0.038). A sham experiment revealed that the blood in this experimental preparation contributed less than 10% to the total clearance of dopamine. This study revealed that our isolated in situ model is an excellent method to evaluate the role of the lungs in drug removal. Furthermore, it confirmed that the lungs contribute to the clearance of dopamine from the body.