Cardiac Active Principles in Blood Plasma

Abstract

A study of isolated frog hearts suggests that the amphibian heart is provided normally with a substance that maintains contractility and that disappears slowly from the heart during perfusion with saline solution. A search for substances that might fulfill this role in the frog heart has led to the isolation of many materials that have some degree of cardiotonic activity, but no conclusion can yet be reached about which, if any, of these substances is present in. the intact frog heart. The search has led, however, to the discovery of 2 substances of mammalian origin that are as potent as the cardiac glycosides with respect to their inotropic action on frog heart. One of these is a phospholipid called lysolecithin, the other is a system of 3 plasma globulins called "cardioglobulin A, B, and C." The concentration of cardioglobulin C in man is increased in essential hypertension and aortic stenosis, 2 unrelated conditions that have in common the development of increased left ventricular isometric tension in systole. Conversely, cardioglobulin C is decreased in a group of patients with idiopathic congestive heart failure. The discovery of these substances is relevant to the question whether isolated mammalian cardiac tissue becomes hypodynamic in physiologic saline because of the loss of a system that helps maintain normal myocardial contractility. We have noted that most of the studies on isolated strips of mammalian cardiac tissue fail to answer this question, since the strips were probably hypodynamic because of impaired oxygenation or nonphysiologie saline media. Studies from our laboratory indicate that a slow decline in contractility on prolonged washing does occur in isolated mammalian heart tissue, despite good oxygenation and a normal environment with respect to inorganic ions. This can be prevented or reversed by perfusion with mammalian plasma. Along similar lines, it is of interest that, although the decline of performance characteristics of in situ mammalian hearts may be due to many factors, the decline can be prevented by perfusing the coronary system of the in situ heart with blood from a healthy donor animal. The problem, then, has 2 aspects. On the one hand, we must discover the physiologic significance of the potent glycoside-like substances already isolated from mammalian tissue; on the other, we must investigate the beneficial effects of plasma on heart strips or of donor dog blood on in situ hearts. Do these actions occur because of an effect on myocardial metabolism or do they come about because of a plasma substance that enhances myocardial contractility directly?