Isolation of “Myocardial Depressant Factor(s)” From the Ultrafiltrate of Heart Failure Patients With Acute Renal Failure

Abstract

Cardiac function improvement seen with hemofiltration may be attributable to "cardiac depressant factor(s)" removal. The authors have attempted "factor" isolation. Initial 12 hr hemofiltrate was obtained from: 4 patients with acute congestive heart failure (cardiac index: 2.02 +/- 0.48) and acute renal failure (blood urea nitrogen [BUN] 97.7 +/- 32.7; serum creatinine [SCr] 6.2 +/- 3.4 mg%) (Group I); 8 patients with chronic congestive heart failure (CI: 2.69 +/- 1.3) and mild renal failure (BUN 48.8 +/- 31.4; SCr 3.5 +/- 2.4 mg%) (Group II); and 8 patients with end-stage renal disease and no congestive heart failure (Group III). Crude samples were passed through C18Sep-Pak, and eluted with methanol/water mixtures, and 50% methanol samples were fractionated by high pressure liquid chromatography. Inotropic response was studied by injecting samples (in Krebs-Hensleit buffer) into a Langendorff rat heart preparation. The effect of pH, acetate, salts, and adding propranolol on the inotropic response also was tested. Myocardial depression followed all vehicle and preparatory elements: 0.1 M HCl (-47%); 0.08 M acetic acid (-75%); Na acetate (-25%); 0.1 M NaHCO3 (-11%); Na citrate (-84%); and Na glutarate (-14%). Group I had biphasic responses, the positive inotropism accorded to catecholamines, whereas negative inotropism was equal in each patient (-40.3%). Group II had a biphasic response with negative (-15%) inotropism noted. Group III was weakly biphasic. The data indicate there was myocardial depressive activity, most pronounced in Groups I and II, after method interference was corrected.