POSTREST CONTRACTION AMPLITUDE IN MYOCYTES FROM FAILING HUMAN VENTRICLE

It has been reported that the balance between the two main Ca2+ remova l systems in the cardiac cells, the sarcoplasmic reticulum (SR) and Na +/Ca2+ exchanger, is altered in failing human heart. We have studied p ostrest contraction behaviour as a noninvasive probe of the amount of Ca2+ stored in the SR in myocytes from failing and non-failing human v entricle. The first beat following a rest interval, as a percentage of the preceding steady state (B1/SS), was larger and more variable in c ells from failing heart, indicating some accumulation of Ca2+ in the S R during rest. This could be mimicked by treatment of myocytes with di goxigenin, a compound which increases intracellular Na+, suggesting th at alterations in the Na+ balance of the cell might contribute to the effect. Isoprenaline, which stimulates Ca2+ uptake by the SR while the myocyte is beating, prevented SR Ca2+ accumulation during rest in sus ceptible myocytes. We hypothesize that loss of SR function in the fail ing heart is partially compensated for by increased Ca2+ extrusion via the Na+/Ca2+ exchange in the contracting myocyte, leading to increase d intracellular Na+ during activity. This Na+ is lost at rest, predisp osing the cells to accumulate Ca2+ in the SR. Experiments to test this hypothesis are proposed.