The impact of statin therapy and aerobic exercise training on skeletal muscle and whole-body aerobic capacity.

BACKGROUND: Statin use is widely recognized for improving cardiovascular health, but questions remain on how statin use influences skeletal muscle, particularly mitochondrial function. STUDY OBJECTIVE DESIGN AND PARTICIPANTS: The influence of statin therapy and exercise (EX) on aerobic capacity was determined. In Study1, skeletal muscle aerobic capacity was measured before and after 80 mg atorvastatin therapy. In Study2, aerobic capacity (skeletal muscle and whole body) was measured before and after a 12-week exercise randomized control trial in older adults (age = 67 ± 5 yrs.), a subset of which were on chronic low-moderate intensity statin therapy. MAIN OUTCOME MEASURES: Muscle oxidative capacity was determined from the phosphocreatine recovery rate constant (kPCr) using 31P Magnetic Resonance Spectroscopy. Whole body peak oxygen uptake (VO2 peak) was measured during a graded exercise test with indirect calorimetry. RESULTS: High dose statin therapy resulted in a 12% reduction in muscle oxidative capacity (pre = 1.34 ± 0.34 min-1, post = 1.17 ± 0.25 min-1, p = 0.004). Similarly, chronic low-moderate dose statin therapy was associated with lower muscle oxidative capacity at baseline (1.50 ± 0.35 min-1) compared to non-statin users (1.88 ± 0.047 min-1, p = 0.019). Following EX, muscle oxidative capacity increased by 35-40% (statin: Pre: 1.39 ± 0.44 vs. Post: 1.88 ± 0.47 min-1, no statin Pre: 1.86 ± 0.58 vs. Post: 2.58 ± 0.85 min-1) compared to control groups (Pre: 1.74 ± 0.27 vs Post: 1.75 ± 0.49 min-1, p = 0.001). VO2 peak increased by 11% for EX groups (Pre: 18.8 ± 2.8 vs. Post: 20.8 ± 3.0 ml·kg-1·min-1) following training compared to a small decline in controls (Pre: 21.8 ± 3.7 vs. Post: 20.8 ± 3.04 ml·kg-1·min-1, p = 0.001). CONCLUSIONS: Statin therapy resulted in reduced muscle oxidative capacity. Aerobic exercise improved skeletal muscle oxidative capacity and whole-body aerobic capacity during statin therapy.

Effects of altered pyruvate dehydrogenase activity on contracting skeletal muscle bioenergetics.

During aerobic exercise (>65% of maximum oxygen consumption), the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase (PDH) reaction. This study investigated how regulation of PDH activity affects muscle energetics by determining whether activation of PDH with dichloroacetate (DCA) alters the dynamics of the phosphate potential of rat gastrocnemius muscle during contraction. Twitch contractions were induced in vivo over a broad range of intensities to sample submaximal and maximal aerobic workloads. Muscle phosphorus metabolites were measured in vivo before and after DCA treatment by phosphorus nuclear magnetic resonance spectroscopy. At rest, DCA increased PDH activation compared with control (90 ± 12% vs. 23 ± 3%, P < 0.05), with parallel decreases in inorganic phosphate (Pi) of 17% (1.4 ± 0.2 vs. 1.7 ± 0.1 mM, P < 0.05) and an increase in the free energy of ATP hydrolysis (ΔGATP) (-66.2 ± 0.3 vs. -65.6 ± 0.2 kJ/mol, P < 0.05). During stimulation DCA increased steady-state phosphocreatine (PCr) and the magnitude of ΔGATP, with concomitant reduction in Pi and ADP concentrations. These effects were not due to kinetic alterations in PCr hydrolysis, resynthesis, or glycolytic ATP production and altered the flow-force relationship between mitochondrial ATP synthesis rate and ΔGATP. DCA had no significant effect at 1.0- to 2.0-Hz stimulation because physiological mechanisms at these high stimulation levels cause maximal activation of PDH. These data support a role of PDH activation in the regulation of the energetic steady state by altering the phosphate potential (ΔGATP) at rest and during contraction.

Aerobic Exercise Improves Microvascular Function in Older Adults.

Microvascular function is reduced with age, disease, and inactivity. Exercise is well known to improve vascular health and has the potential to improve microvascular function in aging and disease. PURPOSE: The study aimed to assess changes in peripheral microvascular function in sedentary older adults after aerobic exercise training. METHODS: Twenty-three sedentary older adults (67 ± 5 yr, body mass index = 29 ± 5, mean ± SD) successfully completed a randomized 12-wk graded treadmill walking intervention. The exercise group (EX) performed 40 min of uphill walking 4 d·wk at 70% heart rate reserve. The control group (CON) maintained a sedentary lifestyle for 12 wk. Blood oxygen level-dependent (BOLD) responses of the soleus measured by magnetic resonance imaging were used to evaluate microvascular function; brief (1 s) maximal plantarflexion contractions were performed. Separately, blood flow in the popliteal artery was measured by ultrasound after brief contraction. Phosphorus magnetic resonance spectroscopy of the calf was used to examine muscle oxidative capacity, and whole-body peak oxygen consumption (V˙O2peak) was used to confirm training-induced cardiorespiratory adaptations. RESULTS: Peak postcontraction BOLD response increased by 33% in EX (PRE, 3.3% ± 1.0%; POST, 4.4% ± 1.4%) compared with CON (PRE, 3.0% ± 1.3%; POST, 3.2% ± 1.5%), P < 0.05. EX with hypertension tended to show a blunted peak BOLD increase (n = 6, 15%) compared with EX normotensive (n = 7, 50%), P = 0.056. Peak postcontraction blood flow increased by 39% in EX (PRE, 217 ± 88 mL·min; POST, 302 ± 167 mL·min) compared with CON (PRE, 188 ± 54 mL·min; POST, 184 ± 44 mL·min), P < 0.05. EX muscle oxidative capacity (kPCr) improved by 40% (PRE, 1.60 ± 0.57 min; POST, 2.25 ± 0.80 min) compared with CON (PRE, 1.69 ± 0.28 min; POST, 1.76 ± 0.52 min), P < 0.05. V˙O2peak increased by 9% for EX (PRE, 19.0 ± 3.1 mL·kg·min; POST, 20.8 ± 2.9 mL·kg·min) compared with a 7% loss in CON (PRE, 21.9 ± 3.6 mL·kg·min; POST, 20.4 ± 3.5 mL·kg·min), P < 0.05. CONCLUSION: Moderate aerobic exercise significantly improved microvascular function of the leg in older adults.

Age Reduces Microvascular Function in the Leg Independent of Physical Activity.

The microvasculature is critical in the control of blood flow. Aging and reduced physical activity (PA) may both decrease microvascular function. PURPOSE: The primary aim was to evaluate the influence of age on microvascular function in adults with similar PA levels. Secondary aims were to assess the reliability of muscle functional magnetic resonance imaging in older adults (OA) and the relationship between PA and microvascular function in OA. METHODS: Microvascular blood-oxygen-level dependent (BOLD) responses were measured in young adults (YA, n = 12, mean ± SD age = 21 ± 1 yr old, PA = 239 ± 73 × 10 counts per day) and OA (n = 13, 64 ± 4 yr old, PA = 203 ± 48 × 10 counts per day). Functional magnetic resonance images (3T, echo planar BOLD) of the leg were acquired after brief (1 s) maximal voluntary isometric contractions. The test-retest reliability of BOLD responses and the Pearson correlation between peak BOLD and PA were assessed in a group of OA (OA-r) with a broad range of PA (66 ± 5 yr old, n = 9, PA range = 54 × 10 to 674 × 10 counts per day). RESULTS: Peak BOLD microvascular responses were reduced for OA compared with YA. OA peak BOLD was 27% lower in the soleus (3.3% ± 0.8% OA vs 4.5% ± 1.4% YA; P = 0.017) and 40% lower in the anterior compartment (1.6% ± 0.6% OA vs 2.7% ± 1.1% YA; P = 0.006). Coefficients of variation were 8.6% and 11.8% for peak BOLD in the soleus and anterior compartment, respectively, with an intraclass correlation of 0.950 for both muscle regions. The correlation between peak BOLD and PA was r ≥ 0.715, P ≤ 0.030. CONCLUSIONS: Aging was associated with reduced microvascular function in leg muscles, independent of PA. The findings also revealed good reliability for BOLD magnetic resonance imaging in OA for the soleus and anterior compartment muscles.

Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age.

Long-term or untreated diabetes leads to micro- and macrovascular complications. However, there are few tests to evaluate microvascular function. A postcontraction blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) technique was exploited to measure peripheral microvascular function in diabetics and healthy controls matched with respect to age, body mass index, and physical activity. Postcontraction BOLD microvascular response was measured following 1-s maximal isometric ankle dorsiflexion in individuals with diabetes mellitus type I [DMI, n = 15, age 33 ± 3 yr (means ± SE), median diabetes duration = 5.5 yr] and type II (DMII, n = 16, age 45 ± 2 yr, median duration = 2.4 yr); responses were compared with controls (CONI and CONII). Peripheral macrovascular function of the popliteal and tibial arteries was assessed during exercise hyperemia with phase contrast magnetic resonance angiography following repetitive exercise. There were no group differences as a result of diabetes in peripheral microvascular function (peak BOLD response: DMI = 2.04 ± 0.38% vs. CONI = 2.08 ± 0.48%; DMII = 0.93 ± 0.24% vs. CONII = 1.13 ± 0.24%; mean ± SE), but the BOLD response was significantly influenced by age (partial r = -0.384, P = 0.003), supporting its sensitivity as a measure of microvascular function. Eleven individuals had no microvascular BOLD response, including three diabetics with neuropathy and four controls with a family history of diabetes. There were no differences in peripheral macrovascular function between groups when assessing exercise hyperemia or the pulsitility and resistive indexes. Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health.

Similar mitochondrial activation kinetics in wild-type and creatine kinase-deficient fast-twitch muscle indicate significant Pi control of respiration.

Past simulations of oxidative ATP metabolism in skeletal muscle have predicted that elimination of the creatine kinase (CK) reaction should result in dramatically faster oxygen consumption dynamics during transitions in ATP turnover rate. This hypothesis was investigated. Oxygen consumption of fast-twitch (FT) muscle isolated from wild-type (WT) and transgenic mice deficient in the myoplasmic (M) and mitochondrial (Mi) CK isoforms (MiM CK(-/-)) were measured at 20°C at rest and during electrical stimulation. MiM CK(-/-) muscle oxygen consumption activation kinetics during a step change in contraction rate were 30% faster than WT (time constant 53 ± 3 vs. 69 ± 4 s, respectively; mean ± SE, n = 8 and 6, respectively). MiM CK(-/-) muscle oxygen consumption deactivation kinetics were 380% faster than WT (time constant 74 ± 4 s vs. 264 ± 4 s, respectively). Next, the experiments were simulated using a computational model of the oxidative ATP metabolic network in FT muscle featuring ADP and Pi feedback control of mitochondrial respiration (J. A. L. Jeneson, J. P. Schmitz, N. A. van den Broek, N. A. van Riel, P. A. Hilbers, K. Nicolay, J. J. Prompers. Am J Physiol Endocrinol Metab 297: E774-E784, 2009) that was reparameterized for 20°C. Elimination of Pi control via clamping of the mitochondrial Pi concentration at 10 mM reproduced past simulation results of dramatically faster kinetics in CK(-/-) muscle, while inclusion of Pi control qualitatively explained the experimental observations. On this basis, it was concluded that previous studies of the CK-deficient FT muscle phenotype underestimated the contribution of Pi to mitochondrial respiratory control.

Quantitative analysis of the postcontractile blood-oxygenation-level-dependent (BOLD) effect in skeletal muscle.

Previous studies show that transient increases in both blood flow and magnetic resonance image signal intensity (SI) occur in human muscle after brief, single contractions, and that the SI increases are threefold larger in physically active compared with sedentary subjects. This study examined the relationship between these transient changes by measuring anterior tibial artery flow (Doppler ultrasound), anterior muscle SI (3T, one-shot echo-planar images, TR/TE = 1,000/35), and muscle blood volume and hemoglobin saturation [near-infrared spectroscopy (NIRS)] in the same subjects after 1-s-duration maximum isometric ankle dorsiflexion contractions. Arterial flow increased to a peak 5.9 ± 0.7-fold above rest (SE, n = 11, range 2.6-10.2) within 7 s and muscle SI increased to a peak 2.7 ± 0.6% (range 0.0-6.0%) above rest within 12 s after the contractions. The peak postcontractile SI change was significantly correlated with both peak postcontractile flow (r = 0.61, n = 11) and with subject activity level (r = 0.63, n = 10) estimated from 7-day accelerometer recordings. In a subset of 7 subjects in which NIRS data acquisition was successful, the peak magnitude of the postcontractile SI change agreed well with SI calculated from the NIRS blood volume and saturation changes (r = 0.80, slope = 1.02, intercept = 0.16), confirming the blood-oxygenation-level-dependent (BOLD) mechanism underlying the SI change. The magnitudes of postcontractile changes in blood saturation and SI were reproduced by a simple one-compartment muscle vascular model that incorporated the observed pattern of postcontractile flow, and which assumed muscle O(2) consumption peaks within 2 s after a brief contraction. The results show that muscle postcontractile BOLD SI changes depend critically on the balance between O(2) delivery and O(2) consumption, both of which can be altered by chronic physical activity.

Comparison of oxidative capacity among leg muscles in humans using gated 31P 2-D chemical shift imaging.

In many small animals there are distinct differences in fiber-type composition among limb muscles, and these differences typically correspond to marked disparities in the oxidative capacities. However, whether there are similar differences in the oxidative capacity among leg muscles in humans is less clear. The purpose of this study was to compare the rate of phosphocreatine (PCr) recovery, a functional in vivo marker of oxidative capacity, in the lateral and medial gastrocnemius, soleus, and the anterior compartment of the leg (primarily the tibialis anterior) of humans. Subjects performed plantar flexion and dorsiflexion gated exercise protocols consisting of 70 sets of three rapid dynamic contractions (<2.86 s) at 20 s intervals (total: 23.3 min). Starting after the sixth set of contractions, (31)P 2-D CSI (8 x 8 matrix, 14-16 cm FOV, 3 cm slice, TR 2.86 s) were acquired via a linear transmit/receive surface coil using a GE 3T Excite System. The CSI data were zero-filled (32 x 32) and a single FID was produced for each time point in the lateral and medial gastrocnemius, soleus, and anterior compartment. The time constant for PCr recovery was calculated from tau = -Deltat/ln[D/(D + Q)], where Q is the percentage change in PCr due to contraction during the steady-state portion of the protocol, D the additional drop in PCr from rest, and Deltat is the interval between contractions. The tau of PCr recovery was longer (p < 0.05) in the anterior compartment (32 +/- 3 s) than in the lateral (23 +/- 2 s) and medial gastrocnemius muscles (24 +/- 3 s) and the soleus (22 +/- 3 s) muscles. These findings suggest that the oxidative capacity is lower in the anterior compartment than in the triceps surae muscles and is consistent with the notion that fiber-type phenotypes vary among the leg muscles of humans.

The postprandial increase in blood triglycerides has no direct effect on the brain BOLD response.

A previous study showed that ingestion of a liquid meal high in polyunsaturated lipids decreased the blood-oxygenation-level-dependent (BOLD) response measured by functional magnetic resonance imaging (fMRI) during a finger-tapping motor task, and suggested that this effect was due to a direct effect of blood lipids on the cerebral vasculature. This study compared the time course and magnitude of the BOLD response in fixed anatomic locations before and 3 h after ingestion of high versus low lipid content liquid meals (235 ml Ensure Plus [Abbot Labs] with or without 50 ml added canola oil). Blood triglyceride content peaked 3 h after the high lipid meal and was elevated by 33% compared with the low lipid meal. There was no significant effect of meal composition on the time course or magnitude of the BOLD response in fixed-location clusters of voxels which were activated during either a motor (finger-tapping), a visual (flashing checkerboard), or an integrative/cognitive (number addition) block-design task paradigm. The results indicate that increased blood total triglyceride content after a meal with relatively high polyunsaturated fat does not directly alter the hemodynamic BOLD response to neural activity. However, the postprandial effect on BOLD response of other meals with varying fat types and amounts, as well as other nutrients and phytochemicals, remains to be determined.

Phosphocreatine recovery kinetics following low- and high-intensity exercise in human triceps surae and rat posterior hindlimb muscles.

Previous studies have suggested the recovery of phosphocreatine (PCr) after exercise is at least second-order in some conditions. Possible explanations for higher-order PCr recovery kinetics include heterogeneity of oxidative capacity among skeletal muscle fibers and ATP production via glycolysis contributing to PCr resynthesis. Ten human subjects (28 +/- 3 yr; mean +/- SE) performed gated plantar flexion exercise bouts consisting of one contraction every 3 s for 90 s (low-intensity) and three contractions every 3 s for 30 s (high-intensity). In a parallel gated study, the sciatic nerve of 15 adult male Sprague-Dawley rats was electrically stimulated at 0.75 Hz for 5.7 min (low intensity) or 5 Hz for 2.1 min (high intensity) to produce isometric contractions of the posterior hindlimb muscles. [(31)P]-MRS was used to measure relative [PCr] changes, and nonnegative least-squares analysis was utilized to resolve the number and magnitude of exponential components of PCr recovery. Following low-intensity exercise, PCr recovered in a monoexponential pattern in humans, but a higher-order pattern was typically observed in rats. Following high-intensity exercise, higher-order PCr recovery kinetics were observed in both humans and rats with an initial fast component (tau < 15 s) resolved in the majority of humans (6/10) and rats (5/8). These findings suggest that heterogeneity of oxidative capacity among skeletal muscle fibers contributes to a higher-order pattern of PCr recovery in rat hindlimb muscles but not in human triceps surae muscles. In addition, the observation of a fast component following high-intensity exercise is consistent with the notion that glycolytic ATP production contributes to PCr resynthesis during the initial stage of recovery.

Short-term high-intensity interval training improves phosphocreatine recovery kinetics following moderate-intensity exercise in humans.

Previous studies have shown that high-intensity training improves biochemical markers of oxidative potential in skeletal muscle within a 2-week period. The purpose of this study was to examine the effect of short-term high-intensity interval training on the time constant () of phosphocreatine (PCr) recovery following moderate-intensity exercise, an in vivo measure of functional oxidative capacity. Seven healthy active subjects (age, 21 +/- 4 years; body mass, 69 +/- 11 kg) performed 6 sessions of 4-6 maximal-effort 30 s cycling intervals within a 2-week period, and 7 subjects (age, 24 +/- 5 years; body mass, 80 +/- 15 kg) served as controls. Prior to and following training, phosphorous-31 magnetic resonance spectroscopy (31P-MRS; GE 3T Excite System) was used to measure relative changes in high-energy phosphates and intracellular pH of the quadriceps muscles during gated dynamic leg-extension exercise (3 cycles of 90 s exercise and 5 min of rest). A monoexponential model was used to estimate the of PCr recovery. The of PCr recovery after leg-extension exercise was reduced by 14% with high-intensity interval training (pretraining, 43 +/- 14 s vs. post-training, 37 +/- 15 s; p < 0.05) with no change in the control group (44 +/- 12 s vs. 43 +/- 12 s, respectively; p > 0.05). These findings demonstrate that short-term high-intensity interval training is an effective means of increasing functional oxidative capacity in skeletal muscle.

Parallel increases in phosphocreatine and total creatine in human vastus lateralis muscle during creatine supplementation.

Short-term creatine supplementation is reported to result in a decreased ratio of phosphocreatine (PCr) to total creatine (TCr) in human skeletal muscle at rest. Assuming equilibrium of the creatine kinase reaction, this decrease in PCr:TCr implies increased cytoplasmic ADP and decreased Gibbs free energy of ATP hydrolysis in muscle, which seems contrary to the reported ergogenic benefits of creatine supplementation. This study measured changes in PCr and TCr in vastus lateralis muscle of adult men (N = 6, 21-35 y old) during and 1 day after 5 d of creatine monohydrate supplementation (0.43 g.kg body weight(-1).d(-1)) using noninvasive 31P and 1H magnetic-resonance spectroscopy (MRS). Plasma and red-blood-cell creatine increased by 10-fold and 2-fold, respectively, by the third day of supplementation. MRS-measured skeletal muscle PCr and TCr increased linearly and in parallel throughout the 5 d, and there was no significant difference in the percentage increase in muscle PCr (11.7% +/- 2.3% after 5 d) vs. TCr (14.9% +/- 4.1%) at any time point. The results indicate that creatine supplementation does not alter the PCr:TCr ratio, and hence the cytoplasmic Gibbs free energy of ATP hydrolysis, in human skeletal muscle at rest.

Elevated skeletal muscle phosphodiesters in adults using statin medications.

Elevated skeletal muscle phosphodiesters (PDE) have previously been reported with muscle-related disorders. Myalgia is a side effect of using statin cholesterol-lowering medications and, therefore, statin use may be associated with increased skeletal muscle PDE. The effect of cholesterol-lowering drugs on skeletal muscle phosphorus metabolites was determined with (31)P magnetic resonance spectroscopy. Resting (31)P metabolites of the anterior compartment muscles were measured in two groups (n = 20; age, 49 +/- 2 years); half were taking statins and the other half were not on these agents. Muscle PDE was 57% greater in the statin group than the control group. These data suggest that statin use increases muscle PDE. Our findings are particularly relevant due to the increasing use and higher dosing of statin medications. Further prospective studies should be performed to document a causal relationship between elevated PDE and statin use, in addition to quantifying correlates to muscle function.

A gated 31P NMR method for the estimation of phosphocreatine recovery time and contractile ATP cost in human muscle.

Muscle phosphocreatine (PCr) recovery time constant (an index of muscle aerobic capacity) and contractile ATP cost were estimated from a gated (31)P NMR protocol which does not require intense, repetitive exercise. Subjects performed 2-s duration, maximum voluntary isometric ankle dorsiflexion contractions at 30-s intervals for 8 min (total 15 contractions), while single-shot (31)P spectra (51.7 MHz, TR 3 s) were acquired from the anterior compartment muscle. Spectra from the sixth through 15th contractions were retrospectively sorted, yielding 10 spectra (each 10 averages) gated to times before and after contraction. There was no significant decrease in muscle pH, allowing the calculation of contractile ATP cost directly from the percentage change in PCr during contraction cycles [8.86 +/- 0.82% (SE, n = 11) of PCr at rest], corresponding to an ATP cost of 1.69 +/- 0.16 mM/s (range 0.99-2.49 mM/s), assuming an 8.2 mM ATP concentration. The time constant for PCr recovery (tau 41.8 +/- 4.2 s, range 22.0-60.8 s) was calculated from tau = -Deltat/ln[D/(D + Q)], where Q is the percentage change in PCr due to contraction, D is the additional steady-state percentage drop in PCr from rest and Deltat is the interval between contractions. In the same subjects, the monoexponential PCr recovery time constant after more intense, repetitive isometric ankle dorsiflexion exercise (30 s at 0.5 Hz, 50% duty cycle) was similar to (36.2 +/- 3.5 s, range 16.5-58.8 s) and well correlated with (r = 0.82) the gated result. In contrast to the gated protocol, muscle pH decreased from 7.01 +/- 0.01 to 6.78 +/- 0.04 during recovery after the repetitive protocol. Hence the gated protocol allows the estimation of muscle ATP cost and PCr recovery without intense exercise or muscle acidification.

Effect of physical activity on MRI-measured blood oxygen level-dependent transients in skeletal muscle after brief contractions.

The signal intensity (SI) in gradient-echo, echo-planar magnetic resonance images (repetition time/echo time = 1,000/40) of anterior tibialis muscle in active [estimated energy expenditure 42.4 +/- 3.7 (SD), n = 8] vs. sedentary (32.3 +/- 0.6 kcal.kg(-1).day(-1), n = 8) young adult (18-34 yr old) human subjects was measured after single, 1-s-duration maximum voluntary ankle dorsiflexion contractions. There was no difference between groups in anterior tibial muscle cross-sectional area or peak force. In both groups there was a transient increase in anterior tibialis muscle SI, which peaked 5-7 s after the end of each contraction. The magnitude of the SI transient was over threefold greater [5.5 +/- 1.0 (SE) vs. 1.5 +/- 0.4%] and persisted twice as long (half-recovery time 5.4 +/- 0.4 vs. 2.7 +/- 0.3 s) in the active subjects. In the same subjects, blood flow in popliteal, anterior tibial, and posterior tibial arteries was measured by cardiac-gated CINE magnetic resonance angiography before and after 2 min of dynamic, repetitive ankle dorsiflexion exercise. There was no difference between groups in resting or postexercise flow in anterior tibial artery, although popliteal and posterior tibial artery flow after exercise tended to be greater in the active group. The results indicate that transient hyperemia and oxygenation in muscle after single contractions are enhanced by chronic physical activity to a greater extent than peak muscle blood flow.

Effect of occupational keyboard typing on magnetic resonance imaging of the median nerve in subjects with and without symptoms of carpal tunnel syndrome.

OBJECTIVE: To examine the effects of occupational keyboard typing on median nerve shape and T2 relaxation and on forearm muscle T2 in professional typists with and without symptoms of carpal tunnel syndrome. DESIGN: Based on the Levine Carpal Tunnel Syndrome Symptom Severity scale (LCTSS), 12 female professional typist volunteers were divided into asymptomatic (LCTSS < 1.3, n = 5) and symptomatic (LCTSS > 1.3, n = 7) groups. Magnetic resonance images were acquired from wrist and forearms of all subjects before, immediately after, and 8 hrs after 3 hrs of typing. Forearm muscle T2 and median nerve T2 cross-sectional area and long/short axis ratio were evaluated by blinded observers. RESULTS: There was no difference between groups in any measured variable before typing. Median nerve T2 increased and long/short axis ratio decreased in asymptomatic subjects after typing, but there were no significant changes in symptomatic subjects. T2 increased in finger flexor muscles after typing, but there was no difference in the pattern of muscle T2 changes between groups. CONCLUSION: In magnetic resonance images of the median nerve at the carpal tunnel, swelling and T2 increases from baseline are a normal response to typing and may be less likely to occur in subjects with symptoms of carpal tunnel syndrome.

Deteriorated geometric structure and strength of the midfemur in men with complete spinal cord injury.

Spinal cord injury (SCI) results in a dramatic loss of bone mineral and a marked increase in fracture incidence in the femur; however, its effect on the femur's geometric structure and strength is poorly studied. The primary purpose of the present study was to assess the geometric structure, composition, and strength of the midfemur in men with long-term (>2 years), complete SCI (C6-L1 level; n=7) relative to men without SCI (n=8). T1-weighted axial images of the thigh were collected on a GE 1.5-T magnetic resonance imager and geometric, structure, composition, and strength measurements of the midfemur and skeletal muscle volume of the midthigh were determined. Areal bone mineral density (aBMD), bone mineral content (BMC), and bone area of the midthird of the femur and arms were determined using dual-energy X-ray absorptiometry. There were no differences in age, height, weight, femur length, arm BMC, arm aBMD, or arm bone area between the SCI group and controls. While the volume of the midfemur was not different in the two groups, the medullary cavity had 53% more volume and was 21-25% wider in the SCI group (P<0.05). In contrast, the cortical wall in the SCI group had a 24% lower volume and was 27-47% thinner (P<0.05). The cortical wall was particularly thin in the posterior section of the bone. The SCI group also had lower BMC and aBMD in the midfemur (21% and 25%, respectively, P<0.05). Calculated cross-sectional moment of inertia (CSMI), section modulus (Z), and polar moment of inertia (J) were lower in the SCI group (13-19%, P<0.05). A higher ratio of cortical bone volume to muscle volume and BMC to muscle volume in the SCI group (P<0.05) suggests that there was a greater loss of muscle than cortical bone after SCI; however, muscle volume was strongly correlated with cortical bone volume and BMC in the SCI and control groups (r=0.71 to 0.90, P<0.05). Muscle volume was also moderately to strongly correlated with CSMI and Z in the anterior-posterior direction and J. Muscle volume was weakly correlated or not correlated with bone strength measures in the control group (P>0.05). These findings suggest that after SCI, the midfemur erodes on the endosteal surface, resulting in a decreased resistance to bending and torsion. Although midthigh muscle volume appears to decline to a greater degree than midfemur cortical bone volume and BMC, their relationships remain strong.

31P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1.

Metabolic control within skeletal muscle is designed to limit ADP accumulation even during conditions where ATP demand is out of balance with ATP synthesis. This is accomplished by the reactions of adenylate kinase (AK; ADP+ADP <--> AMP+ATP) and AMP deaminase (AMP+H(2)O --> NH(3)+IMP), which limit ADP accumulation under these conditions. The purpose of this study was to determine whether AK deficiency (AK(-/-)) would result in sufficient ADP accumulation to be visible using (31)P-NMRS during the high energy demands of frequent in situ tetanic contractions. To do this we examined the high-energy phosphates of the gastrocnemius muscle in the knockout mouse with AK1(-/-) and wild-type (WT) control muscle over the course of 64 rapid (2/s) isometric tetanic contractions. Near-complete depletion of phosphocreatine was apparent after 16 contractions in both groups. By approximately 40 contractions, ADP was clearly visible in AK1(-/-) muscle. This transient concentration of the NMR visible free ADP was estimated to be approximately 1.7 mM, and represents the first time free ADP has been directly measured in contracting skeletal muscle. Such an increase in free ADP is severalfold greater than previously thought to occur. This large accumulation of free ADP also represents a significant reduction in energy available from ATP, and has implications on cellular processes that depend on a high yield of energy from ATP such as calcium sequestration. Remarkably, the AK1(-/-) and WT muscles exhibited similar fatigue profiles. Our findings suggest that skeletal muscle is surprisingly tolerant to a large increase in ADP and by extension, a decline in energy from ATP.