Reduced specific force in patients with mild and severe facioscapulohumeral muscular dystrophy.

BACKGROUND: Specific force, that is the amount of force generated per unit of muscle tissue, is reduced in patients with facioscapulohumeral muscular dystrophy (FSHD). The causes of reduced specific force and its relation with FSHD disease severity are unknown. METHODS: Quantitative muscle magnetic resonance imaging (MRI), measurement of voluntary maximum force generation and quadriceps force-frequency relationship, and vastus lateralis muscle biopsies were performed in 12 genetically confirmed patients with FSHD and 12 controls. RESULTS: Specific force was reduced by ~33% in all FSHD patients independent of disease severity. Quadriceps force-frequency relationship shifted to the right in severe FSHD compared to controls. Fiber type distribution in vastus lateralis muscle biopsies did not differ between groups. CONCLUSIONS: Reduced quadriceps specific force is present in all FSHD patients regardless of disease severity or fatty infiltration. Early myopathic changes, including fibrosis, and non-muscle factors, such as physical fatigue and musculoskeletal pain, may contribute to reduced specific force.

Cerebrovascular CO2 reactivity and dynamic cerebral autoregulation through the eighth decade of life and their implications for cognitive decline.

Aging is accompanied by a decrease in cerebral blood flow (CBF), especially in the presence of preclinical cognitive decline. The role of cerebrovascular physiology including regulatory mechanisms of CBF in processes underlying aging and subclinical cognitive decline is, however, not fully understood. We explored changes in cerebrovascular CO2 reactivity and dynamic cerebral autoregulation (dCA) through the eighth decade of life, and their relation with early cognitive decline. After 10.9 years, twenty-eight (age, 80.0 ± 3.5 years; 46% female) out of forty-eight healthy older adults who had participated in a previous study (age at baseline, 70 ± 4 years; 42% female), underwent repeated transcranial Doppler assessments. Linear mixed-model analyses revealed small reductions in cerebrovascular CO2 reactivity with aging (-0.37%/mmHg, P = 0.041), whereas dCA was modestly enhanced (gain: -0.009 cm/s/mmHg, P = 0.038; phase: +8.9 degrees, P = 0.004). These changes were more pronounced in participants who had developed subjective memory complaints at follow-up. Our observations confirm that dCA is not impaired in aging, despite lower cerebral perfusion and cerebrovascular reactivity. Altogether, this unique longitudinal study highlights the involvement of cerebrovascular health in preclinical cognitive decline, which is of clinical relevance in the development of dementia management strategies.

Analysis of human neutrophil phenotypes as biomarker to monitor exercise-induced immune changes.

The amplitude of the innate immune response reflects the degree of physiological stress imposed by exercise load. An optimal balance of exercise intensity and duration is essential for a balanced immune system and reduces the risk of dysfunction of the immune system. Therefore, it is hypothesized that neutrophils, as key players in the innate immune system, can be used as biomarker in detecting overtraining. The aim was to monitor the state of the innate immune system by phenotyping neutrophils during consecutive bouts of prolonged exercise. Study subjects were recruited from a cohort of walkers participating in a walking event on 3 consecutive days. Participants with immune deficiencies were excluded. Questionnaires to determine the physiological status of the participants were completed. Analysis of neutrophil receptor expression was done by a point-of-care fully automated flow cytometer. A total of 45 participants were recruited, of whom 39 participants were included for data analysis. Study participants had a median age of 64 (58-70) years. The absolute numbers CD16dim /CD62Lbright and CD16bright /CD62Ldim neutrophils were increased after the first 2 days of exercise followed by an adaptation/normalization after the third day. Participants with activated neutrophils (high CD11b expression) had an impaired physical feeling indicated by the participant on a lower visual analog scale compared to participants who did not have activated neutrophils (P = 0.017, P = 0.022). Consecutive days of prolonged exercise results in an initial systemic innate immune response, followed by normalization/adaptation. Increased neutrophil activation was associated with impaired physical feeling measured by a validated VAS score indicated by the participant. Fully automated point-of-care flow cytometry analysis of neutrophil phenotypes in a field laboratory might be a useful tool to monitor relevant differences in the systemic innate immune response in response to exercise.

Muscle fiber dysfunction contributes to weakness in inclusion body myositis.

Atrophy and fatty infiltration are important causes of muscle weakness in inclusion body myositis (IBM). Muscle weakness can also be caused by reduced specific force; i.e. the amount of force generated per unit of residual muscle tissue. This study investigates in vivo specific force of the quadriceps and ex vivo specific force of single muscle fibers in patients with IBM. We included 8 participants with IBM and 12 healthy controls, who all underwent quantitative muscle testing, quantitative MRI of the quadriceps and paired muscle biopsies of the quadriceps and tibialis anterior. Single muscle fibers were isolated to measure muscle fiber specific force and contractile properties. Both in vivo quadriceps specific force and ex vivo muscle fiber specific force were reduced. Muscle fiber dysfunction was accompanied by reduced active stiffness, which reflects a decrease in the number of attached actin-myosin cross-bridges during activation. Myosin concentration was reduced in IBM fibers. Because reduced specific force contributes to muscle weakness in patients with IBM, therapeutic strategies that augment muscle fiber strength may provide benefit to patients with IBM.

Benefits of lifelong exercise training on left ventricular function after myocardial infarction.

Background Endurance exercise training induces cardio-protective effects, but athletes are not exempted from a myocardial infarction. Evidence from animal studies suggests that exercise training attenuates pathological left ventricular remodelling following myocardial infarction. We tested the hypothesis that lifelong exercise training is related to attenuated pathological left ventricular remodelling after myocardial infarction as evidenced by better left ventricular systolic function in veteran athletes compared to sedentary peers. Design This was a cross-sectional study. Methods Sixty-five males (60 ± 6 years) were included and allocated to four groups based on lifelong exercise training volumes: (a) athletes ( n = 18), (b) post-myocardial infarction athletes (athletes + myocardial infarction, n = 20), (c) sedentary controls ( n = 13), and (d) post-myocardial infarction controls (sedentary controls + myocardial infarction, n = 14). Athletes were lifelong (≥20 years) highly physically active (≥30 metabolic equivalent of task (MET)-h/week), whereas sedentary controls did not meet the exercise guidelines (<10 MET-h/week) for the past 20 years. left ventricular systolic function, diastolic function and wall strain were measured using echocardiography. Results Cardiac enzyme markers (creatine-kinase, creatinine, aspartate transaminase and lactate dehydrogenase) following myocardial infarction and infarct location did not differ between athletes + myocardial infarction and sedentary controls + myocardial infarction. Left ventricular ejection fraction was significantly higher in athletes (61% ± 4), athletes + myocardial infarction (58% ± 4) and sedentary controls (57% ± 6) compared to sedentary controls + myocardial infarction (51% ± 7; p < 0.01). Left ventricular circumferential strain was superior in athletes (-19% (-21% to -17%), athletes + myocardial infarction (-16% (-20% to -12%)), and sedentary controls (-15% (-18% to -14%) compared to sedentary controls + myocardial infarction (-13% (-15% to -8%), p < 0.01). Diastolic function parameters did not differ across groups. Conclusion These findings suggest that lifelong exercise training may preserve left ventricular systolic function and possibly attenuates or minimises the deleterious effects of pathological post-myocardial infarction left ventricular remodelling in veteran athletes.

Maximum Inspiratory Pressure is a Discriminator of Pneumonia in Individuals With Spinal-Cord Injury.

BACKGROUND: Respiratory complications remain a major cause of mortality among individuals with spinal-cord injury (SCI). The present study investigated whether respiratory function is a discriminator of pneumonia in individuals with SCI and is aimed to determine the best predictive parameter. METHODS: This was a retrospective cohort study. Individuals with traumatic SCI, level C3 to T12, complete and incomplete lesions, were included. Data on respiratory function were extracted from medical records. The receiver operating characteristic curve was calculated for each parameter (forced vital capacity, FEV1, peak expiratory flow, and maximum inspiratory and expiratory pressure [PImax and PEmax]) to determine the discriminator with the largest area under the curve between individuals with and without pneumonia. RESULTS: Data of 307 subjects were analyzed. PImax was identified as the best discriminator between individuals with and without pneumonia, both in motor complete (area under the curve 0.86, 95% CI 0.78-0.93, P < .001) and incomplete individuals (area under the curve 1.0, 95% CI 1.00-1.00, P < .001). In individuals with motor complete lesions, the threshold value for PImax was 115% of the lesion-specific reference value (sensitivity 74.4%, specificity 83.4%). In motor incomplete individuals, the PImax threshold value was 93.5 cm H2O (sensitivity 100%, specificity 100%). CONCLUSIONS: PImax is the best discriminator between spinal cord-injured individuals with versus those without pneumonia. Individuals with a PImax below threshold values are at risk of pneumonia.

Impact of prolonged walking exercise on cardiac structure and function in cardiac patients versus healthy controls.

BACKGROUND AND DESIGN: Previous studies have demonstrated that endurance exercise can cause an acute transient decrease in cardiac function in healthy subjects. Whether this also occurs in cardiac patients is unknown. We investigated the impact of prolonged single day and three-day walking exercise on cardiac function and cardiac biomarkers between cardiac patients and healthy controls in an observational study. METHODS: We recruited 10 cardiac patients (nine males, one female, 68 ± 5 years) and 10 age- and sex-matched healthy control subjects (nine males, one female, 68 ± 4 years) to perform 30 or 40 km of walking exercise per day for three consecutive days. Cardiac function was examined using echocardiography and cardiac biomarkers (cardiac troponin and B-type natriuretic peptide) with blood samples. Data were collected before walking and directly after walking on day 1 and day 3. RESULTS: Post-exercise early systolic tissue contraction velocity of the left ventricle (p = 0.005) and global longitudinal left ventricle strain (P = 0.026) were increased in both groups compared with baseline. Post-exercise right ventricle peak early diastolic tissue filling velocity and systolic blood pressure/left ventricle end-systolic volume ratio decreased in both groups (p = 0.043 and p = 0.028, respectively). Post-exercise cardiac troponin levels increased (p = 0.045) but did not differ across groups (p = 0.60), whereas B-type natriuretic peptide levels did not change (p = 0.43). CONCLUSION: This study suggests that stable cardiac patients are capable of performing three days of prolonged walking exercise without clinically significant acute overall deterioration in cardiac function or more pronounced increase in cardiac biomarkers compared with healthy controls.

Effects of respiratory muscle endurance training on wheelchair racing performance in athletes with paraplegia: a pilot study.

OBJECTIVE: Respiratory muscle endurance training (RMET) has been shown to improve both respiratory muscle and cycling exercise endurance in able-bodied subjects. Since effects of RMET on upper extremity exercise performance have not yet been investigated, we evaluated the effects of RMET on 10-km time-trial performance in wheelchair racing athletes. DESIGN: Pilot study, controlled before and after trial. SETTING: Spinal cord injury research center. PARTICIPANTS: 12 competitive wheelchair racing athletes. INTERVENTIONS: The training group performed 30 sessions of RMET for 30 min each. The control group did no respiratory muscle training. MAIN OUTCOME MEASUREMENTS: Differences in 10-km time-trial performance pre- versus postintervention. RESULTS: In the training group, the time of the 10-km time-trial decreased significantly from before versus after intervention (27.1 +/- 9.0 vs. 24.1 +/- 6.6 min); this did not occur in the control group (23.3 +/- 2.8 vs. 23.2 +/- 2.4 min). No between groups difference was present (P = 0.150). Respiratory muscle endurance increased significantly within the training group (9.1 +/- 7.2 vs. 39.9 +/- 17.8 min) and between groups, but not within the control group (4.3 +/- 2.9 vs. 6.6 +/- 7.0 min) before versus after intervention. CONCLUSION: There was a strong trend, with a large observed effect size of d = 0.87, towards improved performance in the 10-km time-trial after 6 weeks of RMET.