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 Citations (Scopus)

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
StatePublished - Apr 1 2016

Fingerprint

Cardiac Myocytes
Muscle Cells
Dogs
Myocardium
Cell Aging
Muscular Diseases
Hypertrophy
Action Potentials
Hemodynamics
Phenotype
Muscles
Population

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

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

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 310, No. 7, 01.04.2016, p. H873-H890.

Research output: Contribution to journalArticle

Sorrentino, A, Signore, S, Qanud, K, Borghetti, G, Meo, M, Cannata, A, Zhou, Y, Wybieralska, E, Luciani, M, Kannappan, R, Zhang, E, Matsuda, A, Webster, A, Cimini, M, Kertowidjojo, E, D’Alessandro, DA, Wunimenghe, O, Michler, RE, Royer, C, Goichberg, P, Leri, A, Barrett, EG, Anversa, P, Hintze, TH & Rota, M 2016, 'Myocyte repolarization modulates myocardial function in aging dogs', American Journal of Physiology - Heart and Circulatory Physiology, vol. 310, no. 7, pp. H873-H890. https://doi.org/10.1152/ajpheart.00682.2015
Sorrentino, Andrea ; Signore, Sergio ; Qanud, Khaled ; Borghetti, Giulia ; Meo, Marianna ; Cannata, Antonio ; Zhou, Yu ; Wybieralska, Ewa ; Luciani, Marco ; Kannappan, Ramaswamy ; Zhang, Eric ; Matsuda, Alex ; Webster, Andrew ; Cimini, Maria ; Kertowidjojo, Elizabeth ; D’Alessandro, David A. ; Wunimenghe, Oriyanhan ; Michler, Robert E. ; Royer, Christopher ; Goichberg, Polina ; Leri, Annarosa ; Barrett, Edward G. ; Anversa, Piero ; Hintze, Thomas H. ; Rota, Marcello. / Myocyte repolarization modulates myocardial function in aging dogs. In: American Journal of Physiology - Heart and Circulatory Physiology. 2016 ; Vol. 310, No. 7. pp. H873-H890.
@article{5a2375cbec77437e991129c3c1abdb75,
title = "Myocyte repolarization modulates myocardial function in aging dogs",
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.",
keywords = "Aging, Contractile reserve, Myocardium",
author = "Andrea Sorrentino and Sergio Signore and Khaled Qanud and Giulia Borghetti and Marianna Meo and Antonio Cannata and Yu Zhou and Ewa Wybieralska and Marco Luciani and Ramaswamy Kannappan and Eric Zhang and Alex Matsuda and Andrew Webster and Maria Cimini and Elizabeth Kertowidjojo and D’Alessandro, {David A.} and Oriyanhan Wunimenghe and Michler, {Robert E.} and Christopher Royer and Polina Goichberg and Annarosa Leri and Barrett, {Edward G.} and Piero Anversa and Hintze, {Thomas H.} and Marcello Rota",
year = "2016",
month = "4",
day = "1",
doi = "10.1152/ajpheart.00682.2015",
language = "English (US)",
volume = "310",
pages = "H873--H890",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "7",

}

TY - JOUR

T1 - Myocyte repolarization modulates myocardial function in aging dogs

AU - Sorrentino, Andrea

AU - Signore, Sergio

AU - Qanud, Khaled

AU - Borghetti, Giulia

AU - Meo, Marianna

AU - Cannata, Antonio

AU - Zhou, Yu

AU - Wybieralska, Ewa

AU - Luciani, Marco

AU - Kannappan, Ramaswamy

AU - Zhang, Eric

AU - Matsuda, Alex

AU - Webster, Andrew

AU - Cimini, Maria

AU - Kertowidjojo, Elizabeth

AU - D’Alessandro, David A.

AU - Wunimenghe, Oriyanhan

AU - Michler, Robert E.

AU - Royer, Christopher

AU - Goichberg, Polina

AU - Leri, Annarosa

AU - Barrett, Edward G.

AU - Anversa, Piero

AU - Hintze, Thomas H.

AU - Rota, Marcello

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - Aging

KW - Contractile reserve

KW - Myocardium

UR - http://www.scopus.com/inward/record.url?scp=84983775755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983775755&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00682.2015

DO - 10.1152/ajpheart.00682.2015

M3 - Article

C2 - 26801307

AN - SCOPUS:84983775755

VL - 310

SP - H873-H890

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 7

ER -