CIRCULATORY MODEL IN METABOLIC STUDIES OF RAPIDLY RENEWED HORMONES - APPLICATION TO ANP KINETICS

In an attempt to identify and quantify the sites of atrial natriuretic peptide (ANP) degradation, a new tracer experiment has been developed . I-125-ANP was injected as a bolus just upstream from the right atriu m, and blood was sampled from two different sites (pulmonary artery an d aorta) in eight cardiac patients. Data were analyzed using a physiol ogically based circulatory model consisting of three blocks in series (right heart, lungs and left heart, and periphery) supplied by the sam e flow (cardiac output, measured by thermodilution); the extraction co efficients of the three blocks and of the whole body could be determin ed from the areas under tracer concentration curves in plasma (AUCs). The values for AUCs (means +/- SD) were 64.8 +/- 9.4 and 65.5 +/- 10.7 % dose.l(-1).min(-1) for pulmonary artery and aorta curves, respective ly; the area under the pulmonary artery curve could be subdivided into the area under the first-pass curve (30.6 +/- 4.7% dose l(-1).min(-1) ) and the area under the recirculating curve (34.0 +/- 7.7% dose.l(-1) .min(-1)). The metabolic clearance rate of I-125-ANP, computed as dose divided by the area under the recirculating curve, was 3.1 +/- 0.7 l/ min, and the whole body extraction was 47.6 +/- 6.6% In our patients w ith myocardial dysfunction, neither right heart block nor lungs and le ft heart block significantly extracted ANP, and periphery block accoun ted for almost all removal of the hormone from the blood.