Myocardial length-force relationship in end stage dilated cardiomyopathy and normal human myocardium: analysis of intact and skinned left ventricular trabeculae obtained during 11 heart transplantations.

Abstract

The Frank-Starling-mechanism (FSM) was analyzed in isolated intact and skinned human left ventricular myocardium obtained from 11 heart transplantations (normal donor hearts (NDH), n = 8; dilated cardiomyopathy (DCM), n = 11). The new technique to utilize muscle strips from normal donor hearts which were actually implanted is described in detail. I) In electrically stimulated left ventricular trabeculae (37 degrees C, oxygenated Krebs-Henseleit solution, supramaximal electrical stimulation, frequency 1 Hz) force development was analyzed as a function of muscle length (NDH = 8; DCM = 11). II) In an additional series left ventricular myocardium was demembranized ("skinned") by Triton-X-100. At different sarcomere lengths and calcium concentrations corresponding to pCa values of 4.3, 5.5, and 8.0 force development was measured (DCM = 11; NDH = 9). I) Developed force increased up to an optimum as a function of muscle length in intact NDH- and DCM-myocardium. However, the relative increment of developed force after any length step was smaller in DCM than in NDH. Near "Lmax" (muscle length associated with maximum developed force) passive resting tension was considerably elevated in DCM, indicating significantly increased diastolic stiffness. II) In skinned left ventricular DCM- and NDH-myocardium developed force depended on sarcomere length with an optimum near 2.2 microns. However, a reduction of activator calcium concentration from pCa 4.3 to pCa 5.5 produces a smaller percent decline in force at short sarcomere lengths in DCM than it does in NDH. The present study shows that except for diastolic stiffness and a smaller relative force increment after any length step in DCM the Frank Starling mechanism is still present in isolated human left ventricular DCM- as in NDH-myocardium. The current study does not allow to decide whether in skinned myocardium the smaller percent decline in force after reduction of activator calcium concentrations in DCM is caused by an increased calcium sensitivity at short sarcomere lengths or decreased sensitivity at long sarcomere lengths.