LENGTH DEPENDENCE OF CALCIUM-TRANSIENTS AND FORCE-TRANSIENTS IN NORMAL AND FAILING HUMAN MYOCARDIUM

Two questions were analysed: (1) Is the Frank-Starling mechanism opera tive 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 stimulat ed left-ventricular trabeculae [normal donor heart (NDH), n=8; end sta ge dilated cardiomyopathy (DCM), n=11], isometric force development wa s analysed as a function of muscle length (37 degrees C, oxygenated Kr ebs-Henseleit solution, supramaximal electrical stimulation, frequency : 1 Hz). (II) Myocardium from the same patients were loaded with the f luorescent dye FURA-2/AM for simultaneous measurements of intracellula r calcium transient (ICT) and force development at different muscle le ngths. 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 len gth in NDH- and DCM-myocardium. The slope of this increase was flatter in DCM-myocardium (P<0.01). (II) In NDH- and DCM-myocardium, diastoli c and systolic calcium increased significantly with muscle length. Wit h decreasing muscle lengths the ICT became broader, the diastolic deca y was retarded and the peak of the ICT was natter. At L-max the calciu m amplitude was 23% smaller in DCM than in NDH (P<0.04). Conclusion: t here is a clear length dependence of active force in DCM-myocardium. T he length dependence of farce development is associated with length-de pendent modulations of the ICT. The natter slope of the length-force c urve in DCM may be partly explained by altered intracellular calcium h andling in failing myocardium. (C) 1998 Academic Press Limited.