Myocardial Alterations in Senescent Mice and Effect of Exercise Training

Author:

Derumeaux Geneviève1,Ichinose Fumito1,Raher Michael J.1,Morgan John G.1,Coman Tereza1,Lee Candace1,Cuesta Jose Maria1,Thibault Hélène1,Bloch Kenneth D.1,Picard Michael H.1,Scherrer-Crosbie Marielle1

Affiliation:

1. From the Inserm U886 (G.D., H.T.), Université Claude Bernard Lyon I, Lyon, France; and Department of Anesthesia (F.I., M.J.R., K.D.B.), Cardiac Ultrasound Laboratory (G.D., M.J.R., J.G.M., T.C., C.L., J.M.C., M.P., M.S.-C.), and Cardiovascular Research Center (M.J.R., K.D.B., M.S.-C.), Massachusetts General Hospital, Boston, Mass.

Abstract

Background— Aging is accompanied by an alteration in myocardial contractility. However, its noninvasive detection is difficult. The effect of chronic exercise on this decrease is unknown. Murine models of senescence are increasingly used to test therapies in aging. We tested whether strain rate imaging detected left ventricular (LV) systolic dysfunction in aging mice and was able to assess a potential improvement after exercise. Methods and Results— Young (3 weeks), adult (2 to 3 months), and old (6 to 18 months) C57BL6 male mice underwent echocardiograms with strain rate imaging, either in sedentary conditions or before, 2 weeks and 4 weeks after chronic swimming. Hemodynamic parameters of LV function including maximal and end-systolic elastance were obtained before euthanizing. LV fibrosis was measured using Sirius red staining. Conventional echocardiography was unable to detect LV systolic dysfunction in old mice, whereas both systolic strain rate and load-independent hemodynamic parameters such as preload recruitable stroke work and end-systolic elastance were significantly decreased. Both strain rate and load-independent hemodynamic parameters normalized after 4 weeks of exercise. Both endocardial and epicardial fibrosis were increased in the LV of aging mice. Endocardial fibrosis decreased in exercised aged mice. Conclusions— Strain rate noninvasively detects LV systolic dysfunction associated with aging in mice, whereas conventional echocardiography does not. Chronic exercise normalizes LV systolic function and decreases fibrosis in old mice. Strain rate imaging in mice may be a useful tool to monitor the effect of new therapeutic strategies preventing the myocardial dysfunction associated with aging.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Radiology Nuclear Medicine and imaging

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