Length Dependence of Calcium- and Force-Transients in Normal and Failing Human Myocardium

Two questions were analysed: (1) Is the Frank–Starling mechanism operative in failing human myocardium? (2) Are length-dependent changes in force accompanied by length-dependent changes in intracellular calcium transients in human myocardium? Methods: (I) in electrically stimulated left-ventricular trabeculae [normal donor heart (NDH),n=8; end stage dilated cardiomyopathy (DCM),n=11], isometric force development was analysed as a function of muscle length (37°C, oxygenated Krebs–Henseleit solution, supramaximal electrical stimulation, frequency: 1 Hz). (II) Myocardium from the same patients were loaded with the fluorescent dye FURA-2/AM for simultaneous measurements of intracellular calcium transient (ICT) and force development at different muscle lengths. Muscle length, resting force, developed force and intracellular Calcium (“ratio method”) were monitored continuously. Results: (I) developed force increased up to an optimum as a function of muscle length in NDH- and DCM-myocardium. The slope of this increase was flatter in DCM-myocardium (P<0.01). (II) In NDH- and DCM-myocardium, diastolic and systolic calcium increased significantly with muscle length. With decreasing muscle lengths the ICT became broader, the diastolic decay was retarded and the peak of the ICT was flatter. At Lmaxthe calcium amplitude was 23% smaller in DCM than in NDH (P<0.04). Conclusion: there is a clear length dependence of active force in DCM-myocardium. The length dependence of force development is associated with length-dependent modulations of the ICT. The flatter slope of the length–force curve in DCM may be partly explained by altered intracellular calcium handling in failing myocardium.