Circulation Research, Vol 74, 952-958, Copyright © 1994 by American Heart Association

ARTICLES

Intracellular calcium transient of working human myocardium of seven patients transplanted for congestive heart failure

CF Vahl, A Bonz, T Timek and S Hagl
Department of Cardiac Surgery, University of Heidelberg, Germany.

The afterload dependence of the intracellular calcium transient in isolated working human myocardium was analyzed in both donor and recipient hearts of seven patients undergoing transplantation because of dilated cardiomyopathy. The intracellular calcium transient (recorded by the fura 2 ratio method), force development, and muscle shortening were simultaneously recorded in small (0.6 x 4.0-mm) electrically driven (60 beats per minute) trabeculas contracting at constant preload against varying afterloads. When the fibers contracted under isometric conditions, the intracellular calcium transients of normal and failing myocardium were similar. However, in dilated cardiomyopathy, stepwise afterload reduction and the concomitant increase in shortening amplitudes were associated with extraordinary alterations in the shape of the calcium transients; the amplitude rose, the time to peak was delayed, and at minimal afterloads, a long-lasting plateau was observed, and the diastolic decay was retarded. The calcium- time integral during shortening against passive resting force was 124 +/- 5% of the isometric control in normal myocardium and 172 +/- 12% in end-stage heart failure (P < .0001). We conclude that adequate interpretation of intracellular calcium transients requires simultaneous recordings of force and shortening. The extraordinary afterload dependence of the calcium transient in end-stage heart failure may be attributed to increased dissociation of calcium from the contractile proteins, a reduced calcium reuptake rate of the sarcoplasmic reticulum, or an increased calcium inflow due to altered permeabilities of the calcium channels during shortening. A potential role of mechanosensitive calcium channels has to be considered.

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