title: Altered ventricular torsion and transmural patterns of myocyte relaxation precede heart failure in aging F344 rats.
abstract: The purpose of this study was to identify and explain changes in ventricular and cellular function that contribute to aging-associated cardiovascular disease in aging F344 rats. Three groups of female F344 rats, aged 6, 18, and 22 mo, were studied. Echocardiographic measurements in isoflurane-anesthetized animals showed an increase in peak left ventricular torsion between the 6- and the 18-mo-old groups that was partially reversed in the 22-mo-old animals (P < 0.05). Epicardial, midmyocardial, and endocardial myocytes were subsequently isolated from the left ventricles of each group of rats. Unloaded sarcomere shortening and Ca(2+) transients were then measured in these cells (n = >75 cells for each of the nine age-region groups). The decay time of the Ca(2+) transient and the time required for 50% length relaxation both increased with age but not uniformly across the three regions (P < 0.02). Further analysis revealed a significant shift in the transmural distribution of these properties between 18 and 22 mo of age, with the largest changes occurring in epicardial myocytes. Computational modeling suggested that these changes were due in part to slower Ca(2+) dissociation from troponin in aging epicardial myocytes. Subsequent biochemical assays revealed a >50% reduction in troponin I phosphoprotein content in 22-mo-old epicardium relative to the other regions. These data suggest that between 18 and 22 mo of age (before the onset of heart failure), F344 rats display epicardial-specific myofilament-level modifications that 1) break from the progression observed between 6 and 18 mo and 2) coincide with aberrant patterns of cardiac torsion.
authors.affiliation: Department of Physiology and the Center for Muscle Biology, University of Kentucky, Lexington, Kentucky.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Campbell
authors.forename: Premi
authors.initials: P
authors.lastname: Haynes
authors.forename: W
authors.initials: W
authors.lastname: Kelsey Snapp
authors.forename: Kristofer E
authors.initials: KE
authors.lastname: Nava
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Campbell
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009126:Muscle Relaxation / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012518:Sarcomeres / Q000473:pathology; D013997:Time Factors; D014102:Torsion Abnormality / Q000473:pathology / Q000503:physiopathology*
chemical_list: D002118:Calcium
keywords: aging; heart failure; left ventricular torsion; transmural heterogeneity