INTRACELLULAR CALCIUM TRANSIENT OF WORKING HUMAN MYOCARDIUM OF 7 PATIENTS TRANSPLANTED FOR CONGESTIVE-HEART-FAILURE

The afterload dependence of the intracellular calcium transient in iso lated working human myocardium was analyzed in both donor and recipien t hearts of seven patients undergoing transplantation because of dilat ed cardiomyopathy. The intracellular calcium transient (recorded by th e fura 2 ratio method), force development, and muscle shortening were simultaneously recorded in small (0.6x4.0-mm) electrically driven (60 beats per minute) trabeculas contracting at constant preload against v arying afterloads. When the fibers contracted under isometric conditio ns, the intracellular calcium transients of normal and failing myocard ium were similar. However, in dilated cardiomyopathy, stepwise afterlo ad reduction and the concomitant increase in shortening amplitudes wer e associated with extraordinary alterations in the shape of the calciu m transients: the amplitude rose, the time to peak was delayed, and at minimal afterloads, a long-lasting plateau was observed, and the dias tolic 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 tra nsients requires simultaneous recordings of force and shortening. The extraordinary afterload dependence of the calcium transient in end-sta ge heart failure may be attributed to increased dissociation of calciu m from the contractile proteins, a reduced calcium reuptake rate of th e sarcoplasmic reticulum, or an increased calcium inflow due to altere d permeabilities of the calcium channels during shortening. A potentia l role of mechanosensitive calcium channels has to be considered.