Characterization of a myocardial depressant factor isolated from dogs with cardiogenic shock

Abstract

Cardiogenic shock was produced in dogs by embolization of the circumflex or anterior descending branches of left coronary artery. The shock plasma was processed through selective ultrafiltration and fractionated by gel-filtration column chromatography into six distinct peaks A, B, C, D, E, and F in the descending order of molecular weights. The fourth peak termed D contained the total MDF (Myocardial Depressant Factor) activity of the row plasma. The control plasma obtained at zero time prior to coronary embolization, yielded none or negligible peak D virtually devoid of myocardial depressant activity. MDF activity of shock peak D samples was determined under the controlled assay condition, and shown to be markedly increased in parallel with progression of shock states. MDF isolated from shock plasma was found to be filtrable, soluble in aqueous media, recovered in the chromatographic fraction of molecular weight range between 800 and 1000, heat stable (i.e. 56 C, 30 min), and to give a positive ninhydrin test. The amino acid analysis of MDF after hydrolysis in 6 N HCl and using an amino acid analyzer, revealed the molecular species composed of alanine, aspartic acid, glutamic acid, glycine, iso-leucine, leucine, serine, threonine, and valine indicating it to be nona- or octapeptide without sulfur-linkage. The observed lysosome abnormalities and ischemic cellular injuries in the pancreas were consistent with the view that the primary site of MDF production is the ischemic viscera, particularly pancreas in which intracellular acidosis causes activation of lysosomal acid proteases to catalyze the degradation of substrate proteins to the peptide. The data presented do suggest MDF may be an important determinant in impairment of myocardial performance during cardiogenic shock, presumably affecting on contractility of the viable non-infarcted portion of the heart muscle.