Indicator dilution measurement of 5-hydroxytryptamine clearance by human lung

Abstract

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.

Indicator Dilution Estimation of Capillary Endothelial Transport

“…In the early applications of this technique (10,21,22) the concentrations of the nontracer mother substrate were not measured, so the accuracy of the estimates of K m and V max were questioned because the actual degree of dilution between inflow and outflow was unknown. Malcorps et al (24) measured the chemical and tracer concentrations, and found almost a twofold difference in K m between the bolus sweep and the steady state technique described above.…”

Drug-Specificity in the Perturbation of Pulmonary Disposition of Serotonin in Rabbit in vivo

“…were determined in each fraction, as previously described [17], Likewise, pulmonary clearance of l4C-5-HT was calculated and expressed as % extraction [ 17], Blood flow, mean pulmonary' transit time and vol ume of distribution (Vd) were calculated from the dye dilution curves by the method of Meier and Zierler [19] and « ///s e t al. [12], In order to quantitate the metabolite of 5-HT, plasma samples were pooled from fractions 6 through 20 and 1 ml of the pooled sample was analyzed for 5-HIAA as previously described [17].…”

Extended Theory of the Early Diffusion of Multiple Indicators: Bounds on Permeability Ratios, With Applications to Intestinal Capillaries

“…The first problem is to calculate the magnitude of PS of the capillary walls of the organ for each diffusible indicator. This quantity may be of clinical interest (Gillis et al 1979). The second problem is to interpret the ratios of the magnitudes of PS pertaining to the several diffusible indicators in the bolus, especially in relation to molecular size (restricted diffusion) or facilitated transport (Crone 1965).…”