Cardiovascular disease (CVD) is the primary cause of mortality in women in developed countries. CVD risk rises with age, yet for women there is a rapid increase in CVD risk that occurs after the onset of menopause. This observation suggests the presence of factors in the middle-aged women that accelerate the progression of CVD independent of chronological aging. Leisure time physical activity (LTPA) is a well-established protective factor against CVD. However, its role in attenuating atherogenic lipid profile changes and CVD risk in post-menopausal women has not been well-established. The present study is part of the Estrogenic Regulation of Muscle Apoptosis (ERMA) study, a population-based cohort study in which middle-aged Caucasian women (47–55) were classified into pre-menopausal, peri-menopausal, and post-menopausal groups based on follicle stimulating hormone levels and bleeding patterns. Comprehensive questionnaires, laboratory visits, anthropometric measurements, and physical activity monitoring by accelerometers were used to characterize the menopausal groups and serum lipid profiles were analyzed to quantify CV (cardiovascular) risk factors. Based on our findings, LTPA may attenuate menopause-associated atherogenic changes in the serum CV risk factors of healthy middle-aged women. However, LTPA does not seem to entirely offset the lipid profile changes associated with the menopausal transition.

In this animal model, we found that repair of chronically torn cuff muscles results in extensive injury throughout the muscle. Based on these findings, we posit that inducing a widespread injury at the time of surgical repair of chronically torn rotator cuff muscles may contribute to the problems of failed repairs or continued progression of fatty degeneration that is observed in some patients that undergo rotator cuff repair. Therapeutic interventions to protect muscle fiber membranes potentially could enhance outcomes for patients undergoing rotator cuff repair. To evaluate this, future studies that evaluate the use of membrane sealing compounds or drugs that upregulate endogenous membrane-sealing proteins are warranted.

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Objectives:Rotator cuff tears are a common source of shoulder pain and disability. Even after surgical repair of these tears, many patients continue to have reduced shoulder function and a progression of intramuscular fatty degeneration. Previous work in a sheep model demonstrated that a slow, progressive lengthening of chronically torn cuff muscles followed by surgical repair of the tendon reversed fatty degeneration and improved muscle function. As patients with chronic cuff tears often experience a shortening of the muscle fibers, it is possible that repairing the torn tendon to its original anatomical footprint induces a massive stretch-induced muscle injury that could contribute to poor outcomes after repair. Evans Blue Dye (EBD) is a water soluble, membrane impermeable dye, that is used to identify muscle fibers that have suffered an injury to their plasma membrane. We hypothesized that, compared with acutely torn and repaired rotator cuff muscles, the substantial stretch that is required to repair a chronically torn and shortened rotator cuff would result in significant muscle fiber damage.Methods:This study was approved by our IACUC. Male Sprague-Dawley retired breeder rats (n=30) were placed into 5 groups: control, sham surgery, acute tear no repair, acute tear and repair, chronic tear no repair and chronic tear and repair, with each modality performed bilaterally (Fig 1A). An intraperitoneal injection of 1% EBD was administered 24 hours before the harvest surgery. At harvest, the supraspinatus muscles of each rat were removed and the length and mass of each muscle was measured. To determine EBD+ fibers the supraspinatus muscles were snap frozen in OCT and the muscles were cryosectioned and incubated with WGA-Lectin-AF488 to mark the extracellular matrix (ECM), DAPI to identify nuclei and EBD was used to identify the fibers with a damaged sarcolemma (Fig 1B-C). A one-way ANOVA (p<0.05) and Tukey’s post-hoc sorting was used to evaluate the differences between groups.Results:Compared with controls, rats that had a chronic supraspinatus tear but did not undergo repair had a 35% decrease in muscle mass compared to controls, while rats that had a chronic tear and also underwent repair had a 24% decrease in wet mass compared to controls (Fig 1D). Both groups of rats that underwent a chronic tear experienced an approximate 20% decrease in supraspinatus length when compared to the muscle length of other groups (Fig 1E). In the sham, acute and chronic tear and repair groups there were a greater number of EBD+ fibers in the mid-distal region of the muscle than in the mid-proximal region (Fig 1F). At the mid-distal end of the control and chronic tear no repair groups there were very few EBD+ fibers, in the sham 27% of the fibers were EBD+ and the remaining groups had almost 90% EBD+ fibers (Fig 1F). At the mid-proximal portion of the muscle the chronic tear and repair group had nearly 70% EBD+ fibers while none of the other groups showed a significant increase in EBD+ fibers over the control group (Fig 1G).Conclusi...