The Isolation from Human Blood Plasma of a Substance Having Positive Inotropic Action on the Isolated Toad Heart.

The positive inotropic action of blood plasma on isolated hearts has been known for a long time (Bowditch, 1871; Ringer, 1885; Clark, 1913; Hajdu, 1957; Hajdu, Leonard & Akers, 1957a; Hajdu, Weiss & Titus, 1957 b), and the observations recorded by various authors suggest that a number of different plasma components are responsible for positive inotropic activity. Hajdu et al. (1957b) isolated a substance with digitalis-like activity from mammalian blood and identified it as a-palmitoyllysolecithin. Hajdu et al. (1957a) found that certain plasma protein fractions isolated from hypertensive patients showed a greater inotropic activity on the isolated amphibian heart than those isolated from normotensives. Tanz (1960a, b), Tanz & Kerby (1961) and Sayers & Solomon (1960) have found that aldosterone was responsible in part for the positive inotropic activity of human plasma. Nayler & McCulloch (1960b) found a heat-stable diffusible factor present in human and animal plasma which possessed positive inotropic activity. In preliminary investigations of the pharmacological properties of this heat-stable diffusible plasma factor we have shown that it improves the efficiency of the isolated toad heart and that it exerts a marked effect on the rate at which tension is produced by isolated toad ventricular muscle. Seasonal variation in the activity of toad plasma was observed, suggesting a hormonal control over the activity of this plasma factor in the toad. The present paper describes the isolation of a substance with inotropic activity from heparintreated human plasma.