Myocardial Alterations in Senescent Mice and Effect of Exercise Training

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.

The relative value of strain and strain rate for defining intrinsic myocardial function

“…However, the interpretation of deformation becomes complex when one moves from the principles of unidirectional forces on single muscle fibers to the multidirectional array of fibers in the human heart, which constantly remodel to adapt to load changes on the one hand and on the other from an isolated system to an intact circulation, where much of the loading conditions of the ventricle are created by the force and extent of ejection itself into a more or less compliant aorta. Early animal studies have proven the intrinsic relationship between strain/strain rate and myocardial contractility using invasive measures of contractility as a gold standard (6,10,24). However, additional studies have shown that both parameters are not only dependent on intrinsic contractile function of the myocardium but are also influenced by ventricular size (17), hypertrophy (8), and load (1,4,22).…”

Strain-Rate Imaging Predicts the Attenuation of Left Ventricular Remodeling Induced by Ischemic Postconditioning After Myocardial Infarction in Mice

“…21 In mice, SR measurements are feasible 11 and accurate to quantify regional myocardial function in different pathological conditions. 22 We previously demonstrated that peak systolic SR obtained with TDI technology was closely correlated with the transmural extent of MI 7 and remained stable during a 4-month follow-up after MI. 10 In the present study, we have shown that SR was also significantly correlated with MI size.…”

“…7 and with previous clinical and experimental studies reporting that strain and SR are less subject to load conditions than conventional measurements. 22,25 In the setting of MI models, the superiority of SR over wall thickening may also be explained by 2 mechanisms: (1) regional wall thickening has been shown to become abnormal only when MI affects 30% to 50% of myocardium, 26 and (2) wall thickening measurements may be affected by tethering of normally contracting neighboring segments. 10 …”

“…22,25 Therefore, we used TDI, which allows accurate measurement of peak systolic SR in murine models with a high frame rate (450/s). We did not use the speckle-tracking technique in our study because this technique using 2D-gray-scale images is limited by a lower frame rate compared with Doppler SR imaging, 27 hampering its use in mice models to measure SR, particularly if the aim is to identify subtle improvements in regional function.…”

Fatiguing exercise initiated later in life reduces incidence of fibrillation and improves sleep quality in Drosophila

“…Most of these studies on the effect of exercise training on cardiac aging have been based on epidemiological and cross-sectional studies, since longitudinal studies across the lifespan of humans are intricate. In addition, improvements to vertebrate cardiac function following endurance training have also been documented in both young and old animals (Suvorava et al 2004;Derumeaux et al 2008). However, studies on cardiac aging across ages in long-term and longitudinal study designs in mammals are also complicated because of their long lifespan and genetic redundancy.…”