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.
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Andrea
authors.initials: A
authors.lastname: Sorrentino
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Sergio
authors.initials: S
authors.lastname: Signore
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York;
authors.forename: Khaled
authors.identifier: http://orcid.org/0000-0003-2943-1245
authors.initials: K
authors.lastname: Qanud
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Giulia
authors.initials: G
authors.lastname: Borghetti
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Marianna
authors.initials: M
authors.lastname: Meo
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Antonio
authors.initials: A
authors.lastname: Cannata
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Ewa
authors.initials: E
authors.lastname: Wybieralska
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Marco
authors.initials: M
authors.lastname: Luciani
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Kannappan
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Eric
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Alex
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Andrew
authors.initials: A
authors.lastname: Webster
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Maria
authors.initials: M
authors.lastname: Cimini
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kertowidjojo
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York;
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessandro
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, New York, New York; and.
authors.forename: Oriyanhan
authors.initials: O
authors.lastname: Wunimenghe
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, New York, New York; and.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Michler
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Christopher
authors.initials: C
authors.lastname: Royer
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Polina
authors.initials: P
authors.lastname: Goichberg
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Edward G
authors.initials: EG
authors.lastname: Barrett
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York;
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hintze
authors.affiliation: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Physiology, New York Medical College, Valhalla, New York; marcello_rota@nymc.edu.
authors.forename: Marcello
authors.initials: M
authors.lastname: Rota
mesh_terms: D000200:Action Potentials; D000375:Aging / Q000502:physiology*; D000818:Animals; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology*; D016276:Ventricular Function
keywords: aging; contractile reserve; myocardium