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Pulmonary extraction of 14 C-5-hydroxytryptamine and 3 H-norepinephrine was estimated in patients undergoing aortocoronary saphenous vein grafting. Identical mixtures of both amines were administered intravenously before cardiopulmonary bypass and again just after bypass. Immediately after each injection, 6 ml of blood was withdrawn into tubing, at a constant rate, simultaneously from both the pulmonary artery and the left atrium. Each set of tubing was then divided into six segments, and the 3 H and 14 C content of each segment was measured. In this manner, total isotope collected and blood isotope concentration as a function of time at the two sampling sites were compared directly. Before bypass in every patient studied, less 5-hydroxytryptamine and norepinephrine were withdrawn on the left than on the right of the lungs, implying pulmonary extraction of both amines. In nine patients, the mean percent extraction was 65 ± 4% for 5-hydroxytryptamine and 23 ± 5% for norepinephrine ( P < 0.005). After bypass, the percent extraction of both norepinephrine and 5-hydroxytryptamine was increased in all but one patient; values for norepinephrine were increased to a realtively greater extent. These data represent a direct demonstration of 5-hydroxytryptamine and norepinephrine extraction by human lungs and also suggest that total cardiopulmonary bypass may alter the process.KEY WORDS lung aortocoronary bypass pulmonary vascular space amine extraction• Both 5-hydroxytryptamine (5-HT) and norepinephrine (NE) are removed, to varying degrees, from the pulmonary vascular space of dog (1-4), cat (5), rat (6, 7), guinea pig (8), and rabbit (9). Pulmonary venous and, thus, systemic arterial blood concentrations of these amines are significantly decreased by passage through the lung. The mechanisms and possible physiological significance of the process are unknown, though it has been suggested (10) that pulmonary clearance prevents vasoactive substances (including both NE and 5-HT) which are present inFrom the

A double indicator dilution method to measure 5-hydroxytryptamine (5-HT) clearance by lungs of anesthetized patients is described. Immediately after a bolus injection of [3H]dextran and [14C]5-HT into the right atrial port of a Swan-Ganz catheter, blood from the radial artery is fractionated and the tritium and carbon-14 of each fraction is measured. The difference between the normalized curves of dextran and 5-HT vs. time reflect the extent to which 5-HT is extracted by the lung. This method gave a mean value of 61 +/- 3% (n = 10) for extraction of 5-HT, compared to 59 +/- 4% measured simultaneously by means of the pulmonary artery-left atrial gradient of 5-HT. Variations among three successive determinations in each patient made postoperatively were not statistically significant. This technique is applicable whenever Swan-Ganz and radial or brachial artery catheters are placed for routine clinical management and, therefore, may have wide application for measurement of pulmonary amine (or kinin) extraction in conscious human subjects or experimental animals. Because pulmonay clearance may be compromised by endothelial damage, 5-HT extraction measured in this manner could reflect early damage to human pulmonary endothelium--perhaps before clinical evidence of damage, such as interstitial edema and respiratory distress, is evident.