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
Cf. Vahl et al., 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, Basic research in cardiology, 92(4), 1997, pp. 261-270
The Frank-Starling-mechanism (FSM) was analyzed in isolated intact and
skinned human left ventricular myocardium obtained from 11 heart tran
splantations (normal donor hearts (NDH), n = 8; dilated cardiomyopathy
(DCM), n = 11). The new technique to utilize muscle strips from norma
l donor hearts which were actually implanted is described in detail. M
ethods: I) In electrically stimulated left ventricular trabeculae (37
degrees C, oxygenated Krebs-Henseleit solution, supramaximal electrica
l stimulation, frequency 1 Hz) force development was analyzed as a fun
ction of muscle length (NDH = 8; DCM = 11). II) In an additional serie
s left ventricular myocardium was demembranized (''skinned'') by Trito
n-X-100. At different sarcomere lengths and calcium concentrations cor
responding to pCa values of 4.3, 5.5, and 8.0 force development was me
asured (DCM = 11; NDH = 9). Results: I) Developed force increased up t
o an optimum as a function of muscle length in intact NDH- and DCM-myo
cardium. However, the relative increment of developed force after any
length step was smaller in DCM than in NDH. Near ''Lmax'' (muscle leng
th associated with maximum developed force) passive resting tension wa
s considerably elevated in DCM, indicating significantly incresed dias
tolic stiffness. II) In skinned left ventricular DCM-and NDH-myocardiu
m developed force depended on sarcomere length with an optimum near 2.
2 mu m. However, a reduction of activator calcium concentration from p
Ca 4.3 to pCa 5.5 produces a smaller percent decline in force at short
sarcomere lengths in DCM than it does in NDH. Conclusion: the present
study shows that except for diastolic stiffness and a smaller relativ
e force increment after any length step in DCM the Frank Starling mech
anism is still present in isolated human left ventricular DCM-as in ND
H-myocardium. The current study does not allow to decide whether in sk
inned myocardium the smaller percent decline in force after reduction
of activator calcium concentrations in DCM is caused by an increased c
alcium sensitivity at short sarcomere lengths or decreased sensitivity
at long sarcomere lengths.