Cross-bridge dynamics in human ventricular myocardium: Regulation of contractility in the failing heart

R. J. Hajjar, J. K. Gwathmey

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72 Scopus citations

Abstract

Background. To investigate whether altered cross-bridge kinetics contribute to the contractile abnormalities observed in heart failure, we determined the mechanical properties of cardiac muscles from control and myopathic hearts. Methods and Results. Muscle fibers from normal (n=5) and dilated cardiomyopathy (n=6) hearts were obtained and chemically skinned with saponin. The muscles were then maximally activated at saturating calcium concentrations. Unloaded shortening velocities (V0) were determined in both groups. V0 in control was 0.72±0.09 L(max)/sec, whereas in myopathic muscles, V0 was 0.41±0.06 L(max)/sec at 22°C. The muscles were also sinusoidally oscillated at frequencies ranging between 0.01 and 100 Hz. The dynamic stiffness of the muscles was calculated from the ratio of force response amplitude to length oscillation amplitude. At low frequencies (<0.2 Hz) the stiffness was constant but was larger in myopathic muscles. In the range of 0.2-1 Hz, there was a drop in the magnitude of dynamic stiffness to approximately one quarter of the low-frequency baseline. This range reflects cross-bridge turnover kinetics. In control muscles, the frequency of minimum stiffness was 0.78±0.06 Hz, whereas it was 0.42±0.07 Hz in myopathic muscles. At higher frequencies, the dynamic stiffness increased and reached a plateau at 30 Hz. There were no differences in the plateau reached between control and myopathic muscles. Conclusions. Because myopathic hearts have a markedly diminished energy reserve, the slowing of the cross-bridge cycling rate plays an important adaptational role in the observed contractility changes in human heart failure. Although the potential to generate maximal Ca2+-activated force is similar in normal and myopathic hearts, alterations in contractile protein composition could explain the diminished cross-bridge cycling rate in failing hearts.

Original languageEnglish
Pages (from-to)1819-1826
Number of pages8
JournalCirculation
Volume86
Issue number6
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • calcium
  • cardiomyopathy
  • cross-bridge kinetics
  • myofilaments

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