Abstract
It is well known that myocardial sodium pump plays an important role in the maintenance of the electrochemical activities of the heart, and it is now becoming apparent that an inhibition of its activity by cardiac glycosides is associated with both positive inotropic and arrhythmogenic effects (see 1 and 2). Many types of effector cells are known to undergo compensatory changes in sensitivity to stimuli and in receptor numbers, particularly the beta-adrenergic receptors, when there is a chronic increase or decrease in the contact between an agonist and the cells. The phenomenon of up and down regulation of sodium pumping sites in myocardium with chronic exposure to cardiac glycosides, as well as the subsequent myocardial sensitivity changes, however, are not well understood. Recently, we and a number of other investigators have also reported significant alterations in the steady-state activity of myocardial sodium pump in various pathological states, such as diabetic, hypertensive, hypothyroid and ischemic (3–7), as well as following various hormonal (insulin and thyroid) and chemical (reserpine) treatments (3, 7–8). The pathophysiological significance of these sodium pump activity alterations in relation to myocardial function and their responsiveness to cardiac glycosides, however, are not clear. Since it is becoming apparent that the remaining uninhibited sodium pump activity in the presence of cardiac glycosides ultimately determines the magnitude of increases in intracellular sodium concentration and the positive inotropic effect of cardiac glycosides, changes in the steady-state sodium pumping sites could thus modulate the sensitivity of cardiac glycosides. In this article we will briefly review the results of our studies on 1) the effects of chronic cardiac glycosides treatment as well as various pathological states, such as diabetes mellitus and acute myocardial ischemia, on myocardial sodium pumping sites, and 2) the sensitivity of these pathological hearts to the inotropic actions of cardiac glycosides.
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