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Related Experiment Videos

Decrease in myocardial ryanodine receptors and altered excitation-contraction coupling early in the development of

D E Vatner1, N Sato, K Kiuchi

  • 1Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass.

Circulation
|September 1, 1994
PubMed
Summary

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Rapid ventricular pacing impairs heart contractility early, affecting calcium release mechanisms. These changes in excitation-contraction coupling are crucial in heart failure development.

Area of Science:

  • Cardiology
  • Physiology
  • Molecular Biology

Background:

  • Rapid ventricular pacing (RVP) initially reduces myocardial contractile function in conscious dogs.
  • Prolonged RVP (4-7 weeks) exacerbates contractile dysfunction, leading to overt congestive heart failure signs.

Purpose of the Study:

  • To investigate the early changes in excitation-contraction coupling during RVP-induced heart failure.
  • To determine the role of sarcoplasmic reticulum calcium release in contractile abnormalities.

Main Methods:

  • Assessed mechanical restitution and postextrasystolic potentiation as indices of calcium release.
  • Measured the response to isoproterenol infusion.
  • Quantified ryanodine receptor and dihydropyridine binding densities and affinities.

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Main Results:

  • Mechanical restitution and postextrasystolic potentiation were depressed after 1 day of RVP.
  • Isoproterenol response was significantly blunted (52%) after 1 day of RVP.
  • 3H-ryanodine receptor binding density decreased significantly after 1 day of RVP and remained low during heart failure.
  • Ryanodine receptor affinity and dihydropyridine binding were unchanged.
  • Physiological responses and ryanodine receptor binding recovered within 5 days after cessation of 1-day RVP.

Conclusions:

  • Early alterations in excitation-contraction coupling, particularly involving the sarcoplasmic reticulum calcium release channel, occur during heart failure development.
  • These early changes are critical in the pathogenesis of contractile dysfunction in heart failure.