ATRIAL-NATRIURETIC-PEPTIDE IS NOT DEGRADED BY THE LUNGS IN HUMANS

In an attempt to identify and quantify the sites of atrial natriuretic peptide (ANP) degradation, particularly the lungs, a new tracer metho d to study ANP metabolism in, vivo in humans was developed and applied to patients with left ventricular dysfunction. Thirteen male, normote nsive, cardiac patients with different degrees of left ventricular myo cardial involvement were enrolled in the study. The study protocol req uired constant infusion (3 patients) or bolus injection (10 patients) of I-125-labeled ANP just upstream of the right atrium and blood sampl ing from different sites (pulmonary artery, aorta, inferior vena cava, and femoral vein) during the hemodynamic study. Data analysis was bas ed on a kinetic model consisting of three blocks in series (right hear t, lungs and left heart, and periphery) supplied by the same plasma no w (plasma cardiac output). Plasma levels of native ANP were measured w ith a sensitive and specific immunoradiometric assay method. ANP value s measured in the aorta (163.9 +/- 144.8 pg/mL, n = 80) were superimpo sable on those measured in the pulmonary artery (161.8 +/- 136.5 pg/mL , n = 80). Negligible extraction of I-125-labeled ANP was found in the lungs and left heart block (on average 0.08 +/-: 3.92%), whereas the peripheral block extraction (46.2 +/- 7.8%) accounted for almost total hormone removal from the blood (whole body extraction was 46.4 +/-: 6 .6%). ANP metabolic clearance rate (3.11 +/- 1.48, range 1.4-6.8 L/min ) declined with the progression of left ventricular dysfunction (plasm a cardiac output 3.46 +/- 1.08, range 1.2-5.7 L/min), and a close corr elation between metabolic clearance rate and cardiac output was eviden t. Our data suggest that lungs do not extract, or extract only very sm all amounts, of labeled ANP administered iv to patients with different degrees of left ventricular myocardial involvement, and whole body ex traction of labeled ANP remains relatively stable with the progression of disease, and the large reductions in clearance values observed in our patients can be ascribed mainly to the reductions in cardiac outpu t.