Myocyte repolarization modulates myocardial function in aging dogs

Andrea Sorrentino, Sergio Signore, Khaled Qanud, Giulia Borghetti, Marianna Meo, Antonio Cannata, Yu Zhou, Ewa Wybieralska, Marco Luciani, Ramaswamy Kannappan, Eric Zhang, Alex Matsuda, Andrew Webster, Maria Cimini, Elizabeth Kertowidjojo, David A. D’Alessandro, Oriyanhan Wunimenghe, Robert E. Michler, Christopher Royer, Polina GoichbergAnnarosa Leri, Edward G. Barrett, Piero Anversa, Thomas H. Hintze, Marcello Rota

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions.

Original languageEnglish (US)
Pages (from-to)H873-H890
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume310
Issue number7
DOIs
Publication statusPublished - Apr 1 2016

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Keywords

  • Aging
  • Contractile reserve
  • Myocardium

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Sorrentino, A., Signore, S., Qanud, K., Borghetti, G., Meo, M., Cannata, A., ... Rota, M. (2016). Myocyte repolarization modulates myocardial function in aging dogs. American Journal of Physiology - Heart and Circulatory Physiology, 310(7), H873-H890. https://doi.org/10.1152/ajpheart.00682.2015