Muscle strength mediates the relationship between mitochondrial energetics and walking performance

Skeletal muscle mitochondrial oxidative capacity declines with age and negatively affects walking performance, but the mechanism for this association is not fully clear. We tested the hypothesis that impaired oxidative capacity affects muscle performance and, through this mechanism, has a negative effect on walking speed. Muscle mitochondrial oxidative capacity was measured by in vivo phosphorus magnetic resonance spectroscopy as the postexercise phosphocreatine resynthesis rate, kPCr , in 326 participants (154 men), aged 24-97 years (mean 71), in the Baltimore Longitudinal Study of Aging. Muscle strength and quality were determined by knee extension isokinetic strength, and the ratio of knee extension strength to thigh muscle cross-sectional area derived from computed topography, respectively. Four walking tasks were evaluated: a usual pace over 6 m and for 150 s, and a rapid pace over 6 m and 400 m. In multivariate linear regression analyses, kPCr was associated with muscle strength (β = 0.140, P = 0.007) and muscle quality (β = 0.127, P = 0.022), independent of age, sex, height, and weight; muscle strength was also a significant independent correlate of walking speed (P < 0.02 for all tasks) and in a formal mediation analysis significantly attenuated the association between kPCr and three of four walking tasks (18-29% reduction in β for kPCr ). This is the first demonstration in human adults that mitochondrial function affects muscle strength and that inefficiency in muscle bioenergetics partially accounts for differences in mobility through this mechanism

Clinical trials that utilize MRS as a biomarker

Magnetic resonance spectroscopy (MRS) is an ideal tool for therapeutic monitoring in clinical trials although its role has not been formally examined. An initial search for the use of MRS in a clinical trials database showed 488 studies; however, many are ongoing and limited information is available about them. Therefore, the results were cross-referenced with the scientific literature to find those studies that have been completed and have produced peer-reviewed publications. This yielded 61 studies, demonstrating that MRS is actively used in clinical trials. Its most frequent use is to study hepatic lipid content. This is followed by studies of skeletal muscle, using both proton and phosphorous MRS, and finally the brain, which surprisingly was the subject of only 15% of the total MRS studies found. A review and summary of these studies is provided to better understand how MRS is used in clinical trials, and to assess its importance as a noninvasive and quantitative biomarker for disease

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Postexercise phosphocreatine resynthesis is slowed in multiple sclerosis

To determine whether skeletal muscle oxidative metabolism is impaired in multiple sclerosis (MS), 31 phosphorus magnetic resonance spectroscopy was used to measure the rate of intramuscular phosphocreatine (PCr) resynthesis following exercise in MS and controls. Thirteen MS patients underwent intermittent isometric tetanic contractions of the dorsiflexor muscles elicited by stimulation of the peroneal nerve. Eight healthy control subjects performed voluntary isometric exercise of the same muscles. During exercise, there were no differences between groups in the fall of either PCr or pH. However, the half‐time (T‐1/2) of PCr recovery following exercise was significantly longer in MS (2.3 ± 0.3 min) compared to controls (1.2 ± 0.1 min, P < 0.02). These data provide evidence of slowed PCr resynthesis following exercise in MS, which indicates impaired oxidative capacity in the skeletal muscle of this group. This finding suggests that intramuscular changes consistent with deconditioning may be important in the altered muscle function of persons with MS. © 1994 John Wiley & Sons, Inc