Annals of Biomedical Engineering

, Volume 28, Issue 8, pp 991–1001

Integration of Cardiac Myofilament Activity and Regulation with Pathways Signaling Hypertrophy and Failure

  • Pieter P. de Tombe
  • R. John Solaro
Article

Abstract

The syndrome of congestive heart failure (CHF) is an entity of ever increasing clinical significance. CHF is characterized by a steady decrease in cardiac pump function, which is eventually lethal. The mechanisms that underlie the decline in cardiac function are incompletely understood. A central theme in solving the mystery of heart failure is the identification of mechanisms by which the myofilament contractile machine of the myocardium is altered in CHF and how these alterations act in concert with pathways that signal cell growth and death. The cardiac myofilaments are a point of confluence of signals that promote the hypertrophic/failure process. Our hypothesis is that a prevailing hemodynamic stress leads to an increased strain on the myocardium. The increased strain in turn leads to miscues of the normal physiological pathway by which heart cells are signaled to match and adapt the intensity and dynamics of their mechanical activity to prevailing hemodynamic demands. These miscues result in a maladaptation to the stressor and failure of the heart to respond to hemodynamic loads at optimal end diastolic volumes. The result is a vicious cycle exacerbating the failure. Cardiac myofilament activity, the ultimate determinant of cellular dynamics and force, is a central player in the integration and regulation of pathways that signal hypertrophy and failure. © 2000 Biomedical Engineering Society.

PAC00: 8719Hh, 8719Ff, 8719Xx, 8719Rr, 8717-d

Integrative physiology Cardiac pump function Hypertrophy Congestive heart failure 

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Copyright information

© Biomedical Engineering Society 2000

Authors and Affiliations

  • Pieter P. de Tombe
    • 1
  • R. John Solaro
    • 1
  1. 1.Department of Physiology and Biophysics and Cardiovascular Science Program, College of MedicineUniversity of Illinois at ChicagoChicago

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