Altered left ventricular performance in aging physically active mice with an ankle sprain injury

Abstract

We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p < 0.0001). Beginning at 6 months of age, interaction (group × age) was noted with LV posterior wall thickness-to-radius ratios (h/r) where h/r increased with age in the ATFL/CFL and SHAMSED mice while the SHAM and CFL mice exhibited decreased h/r with age (p = 0.0002). Passive filling velocity (E wave) was significantly greater in the SHAM mice and lowest for the ATFL/CFL and SHAMSED mice (p < 0.0001) beginning at 9 months of age. Active filling velocity (A wave) was not different between groups (p = 0.10). Passive-to-active filling velocity ratio (E/A ratio) was different between groups (p < 0.0001), with higher ratios for the SHAM mice and lower ratios for the ATFL/CFL and SHAMSED mice in response to physical activity beginning at 9 months of age. Passive-toactive filling velocity ratio decreased with age (p < 0.0001). Regular physical activity throughout the lifespan improved LV structure, passive filling velocity, and E/A ratio by 6 to 9 months of age and attenuated any negative alterations throughout the second half of life. The diastolic filling differences were found to be significantly related to the amount of activity performed by 9 months and at the end of the lifespan.

Lateral Ankle Sprain in a Mouse Model: Lifelong Sensorimotor Dysfunction

“…6 Our results illustrated that consequences persist throughout the lifespan and, when combined with previous reports, demonstrated a broad effect, given that physical activity levels and the cardiovascular system can be negatively affected. 20,21 These findings partially supported our hypotheses because sustaining a single LAS negatively affected sensorimotor function over the lifespan relative to the SHAM group. However, we observed minimal differences between the MILD and SEVERE groups, contrary to our a priori hypotheses.…”

“…Furthermore, the cumulative findings from this model demonstrate that, despite the cultural perspective that an LAS is an innocuous injury, lifelong sequelae persist and manifest as sensorimotor dysfunction, decreased physical activity, 20 and impaired cardiovascular function. 21 However, future research is needed to establish the consistency of the model across different mouse strains because each strain has unique genetic characteristics that could alter the results. For example, the CBA/J strain that we studied has a retinal-degeneration allele that should be considered a limitation of our model on sensorimotor function.…”

“…Therefore, the purpose of our study was to examine the lifelong effects of surgically induced MILD and SEVERE on postural control and locomotor outcomes relative to a control treatment (SHAM) in mice. On the basis of the human CAI and ankle osteoarthritis literature and the work by Hubbard-Turner et al 20 and Turner et al, 21 we hypothesized that the SEVERE would have a more profound effect on postural-control impairments over the entire lifespan than the MILD or SHAM. Similarly, we hypothesized that the SEVERE would have a more profound effect on locomotor outcomes than the MILD or SHAM.…”

Prolonged Rest, Long-Term Dynamic Balance, and Gait in a Mouse Ankle-Sprain Model

“…Mild and severe LAS mouse models have been developed. These models mimic the short-term 16 and residual [17][18][19][20][21] symptoms of mild and severe human LAS, respectively. More specifically, these models have demonstrated both acute and chronic sensorimotor dysfunction as evidenced by impaired dynamic balance and altered gait outcomes.…”

“…More specifically, these models have demonstrated both acute and chronic sensorimotor dysfunction as evidenced by impaired dynamic balance and altered gait outcomes. 16,18,20 As a result, these models [16][17][18][19][20][21] may provide an opportunity to gather preclinical data regarding the effectiveness of LAS interventions, including the effectiveness of prolonged rest or immobilization (or both) on dynamic balance and gait outcomes after a severe LAS. However, the validity of these models in providing insights into the efficacy and effectiveness of therapeutic interventions has not yet been investigated.…”