It has been suggested that a transient limitation in blood flow during intermittent muscular contractions can contribute to muscle fatigue, and that this limitation is greater as contraction ...intensity increases. We investigated skeletal muscle blood flow and fatigue in 13 healthy, untrained men (21-27 years) during 16 min of intermittent (4 s contract, 6 s relax) isometric dorsiflexor contractions. Contractions began at 10% of pre-exercise maximal voluntary contraction (MVC) force and increased by 10% every 2 min. Hyperemia (i.e., post-contraction blood flow, measured by venous occlusion plethysmography) and MVC were measured at the end of each stage. Muscle volume measures were obtained using magnetic resonance imaging. After 10 min of exercise, submaximal force and post-contraction hyperemia plateaued. MVC fell from 8 min of exercise onwards (p=0.004), and this onset of fatigue preceded the plateau in submaximal force and hyperemia. Despite a large range in dorsiflexor muscle size (66.3-176.4 cm(3)) and strength (112.5-421.8 N), neither muscle size nor strength were related to fatigue. The temporal dissociation between changes in blood flow and the onset of fatigue (fall of MVC) suggest that limited blood flow was not a factor in the impaired force production observed during intermittent isometric dorsiflexor contractions in healthy young men. Additionally, post-contraction hyperemia increased linearly with increasing contraction intensity, reflecting a match between blood flow and force production throughout the protocol that was independent of fatigue.
Background
The gold standard clinical trial design is the double-blind, randomized, controlled trial. No standard practice exists for the “unblinding” of trial participants and no legal obligation is ...placed on investigators to inform participants of their treatment allocation or study results at the end of a trial. Here we document our experiences of unblinding the 2520 Scottish participants in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).
Methods
The objectives of the PROSPER unblinding process were to provide all study participants with their study medication status and on-trial cholesterol levels and to respect the rights of participants not to be unblinded. It was considered imperative by the study executive that the blind was maintained until the presentation and publication of the results. Staff therefore remained “blinded” throughout the unblinding process. Inappropriate contact with the PROSPER participants was avoided by confirming their current vital status and health status.
Results
To coincide with the presentation of the PROSPER results, all participants, for whom it was deemed appropriate, were sent a summary of the results and were offered the opportunity to be advised of their treatment allocation and on-trial lipid profiles. The majority of participants opted for telephone unblinding. All primary care physicians who had patients randomised to the study were also sent a summary of the study results and sealed documents detailing the treatment allocation and lipid profiles for each patient. Relocated patients were traced and the information forwarded to their new primary care physicians.
Conclusion
The dissemination of study results and treatment allocation to study participants is an integral part of the research process and should be included in the design of any clinical trial.
The purpose of this study was to estimate the relative contributions of central and peripheral factors to the development of human muscle fatigue. Nine healthy subjects five male, four female; age = ...30 (2) years, mean (SE) sustained a maximum voluntary isometric contraction (MVC) of the ankle dorsiflexor muscles for 4 min. Fatigue was quantitated as the fall in MVC. Three measures of central activation and one measure of peripheral activation (compound muscle action potential, CMAP) were made using electromyography (EMG) and electrical stimulation. Measures of intramuscular metabolism were made using magnetic resonance spectroscopy. After exercise, MVC and electrically stimulated tetanic contraction (50 Hz, 500 ms) forces were 22.2 (3.7)% and 37.3 (7.1)% of pre-exercise values, respectively. The measures of central activation suggested some central fatigue during exercise: (1) the central activation ratio MVC/(MVC + superimposed tetanic force) fell from 0.94 (0.03) to 0.78 (0.09), (2) the MVC/tetanic force ratio fell from 2.3 (0.7) to 1.3 (0.7), and (3) the integral of the EMG (iEMG) signal decreased to 72.6 (9.1)% of the initial value, while the CMAP amplitude was unchanged. Intramuscular pH was associated by regression with the decline in MVC force (and therefore fatigue) and iEMG. The results indicate that central factors, which were not associated with altered peripheral excitability, contributed approximately 20% to the muscle fatigue developed, with the remainder being attributable to intramuscular (i.e., metabolic) factors. The association between pH and iEMG is consistent with proton concentration as a feedback mechanism for central motor drive during maximal effort.
Secretory phospholipase A2 (sPLA2) type IIA and X was analyzed in tumors from 22 patients with colon adenocarcinomas in order
to determine the involvement and activity of sPLA2 in colon cancer. ...Evaluation of immunoreactive sPLA2 IIA by Western blotting
showed a significantly higher level in the periphery of the tumors, compared to central tumor regions. Increased levels of
sPLA2 IIA protein correlated with a two-fold increase in sPLA2 enzymatic activity in the peripheral regions compared to central
regions. Nineteen out of 22 tumors showed high levels of sPLA2 IIA, whereas 7 out of the 22 tumors showed sPLA2 type X. These
data demonstrate that both sPLA2 type IIA and X are present in human colon cancer and suggest a role for sPLA2 in colon cancer
tumor immunology and tumorigenesis.
We tested the hypothesis that, as a result of slower muscle contractile properties, the electromyogram (EMG)/force relationship is decreased during voluntary contractions in older compared to young ...humans. We studied 22 young (32 ± 1 yr, mean ± SE) and 20 older (72 ± 1) men and women. To quantitate ankle dorsiflexor muscle properties, we measured isometric twitch time to peak force and maximal relaxation rate, the rates of tetanic (50 Hz, 1 s) force development and relaxation, and the stimulated force-frequency relationship. The voluntary EMG/force relationship was determined during isometric dorsiflexion from 10% to 100% MVC (maximal voluntary isometric contraction force) in 10% MVC increments. Twitch time to peak force and the rates of tetanic force development and relaxation were slower in the older subjects. Greater relative force was produced in older compared to young adults at 10 Hz. During voluntary contractions, EMG was greater in older compared to young subjects at lower intensities (10% and 20% MVC). Thus, although the older adults exhibited a slowing of contractile properties and summation of force when stimulated at 10 Hz, the voluntary EMG/force relationship was increased rather than decreased at low contraction intensities, compared to young adults. We conclude that the slowing of contractile properties does not result in increased neural “efficiency” of voluntary force production in older adults. This novel observation may have important functional relevance to the performance of activities of daily living, particularly in a more frail older population.
Cluster analysis of muscle functional MRI data Damon, Bruce M; Wigmore, Danielle M; Ding, Zhaohua ...
Journal of applied physiology (1985),
09/2003, Letnik:
95, Številka:
3
Journal Article
Recenzirano
1 Department of Radiology and Radiological
Sciences, Vanderbilt University, Nashville, Tennessee 37232; and
2 Department of Exercise Science, University of
Massachusetts at Amherst, Amherst, ...Massachusetts, 01003
Submitted 20 February 2003
; accepted in final form 20 May 2003
Muscle functional magnetic resonance imaging (mfMRI) is frequently used to
determine spatial patterns of muscle involvement in exercising humans. A
frequent finding in mfMRI is that, even within synergistic muscle groups,
signal intensity (SI) data from individual voxels can be quite heterogeneous.
The purpose of this study was to develop a novel method for organizing
heterogeneous mfMRI data into clusters whose members behave similarly to each
other but distinctly from members of other clusters and apply it in studies of
functional compartmentalization in the anterior compartment of the leg. An
algorithm was developed that compared the SI time courses of adjacent voxels
and grouped together voxels that were sufficiently similar. The algorithm's
performance was verified by using simulated data sets with known regional
differences in SI time courses that were then applied to experimental mfMRI
data acquired from six male subjects (age 22.6 ± 0.9 yr, mean ±
SE) who sustained isometric contractions of the dorsiflexors at 40% of maximum
voluntary contraction. The experimental data were also characterized by using
a traditional analysis (user-specified regions of interest from a single
image), in which the relative change in SI and the contrast-to-noise ratio
CNR; 100% x (SI RESTING - SI ACTIVE )/(noise standard
deviation) were measured. In general, clusters were found in areas in which
the CNR exceeded 5. Cluster analysis made functional distinctions between
regions of muscle that were not seen with traditional analysis. In conclusion,
cluster analysis's use of the full SI time course provides more sensitivity to
muscle functional compartmentation than traditional analysis.
transverse relaxation time constant; image processing; time series; exercise; dorsiflexors
Address for reprint requests and other correspondence: B. M. Damon, Dept. of
Radiology and Radiological Sciences, Vanderbilt Univ. Medical Center, 1161
21st Ave. South-MCN CCC-1121, Nashville, TN 37232-2675 (E-mail:
bruce.damon{at}vanderbilt.edu ).
Skeletal muscle activity is invariably associated with a decline in force-generating capacity (fatigue). The build-up of metabolic by-products such as intracellular H+ and inorganic phosphate (Pi) ...has been shown to be one of the potential mechanisms of muscle fatigue. The use of phosphorus magnetic resonance spectroscopy is a repeatable and useful tool to study the effect of pH and Pi on force development. When maximal exercise is preceded by submaximal exercise to reduce the starting muscle pH and increase Pi, the degree of muscle fatigue correlates more strongly with H2PO4- than pH or Pi alone. However, other studies in humans have found that H2PO4- does not always correlate well with fatigue. The use of ramp exercise protocols allow repeatable and sensitive measurement of changes in muscle metabolism in response to endurance training. Chronic electrical stimulation in dogs and endurance training in humans results in reduced pH and Pi changes at the same exercise intensities. This means that the effect of pH and Pi in depressing force development is reduced, which could partially explain the increased fatigue resistance seen following endurance training.
We used field and laboratory trials to examine the effects of size and species of acorn on food choice by eastern chipmunks (Tamius striatus) from central New York. Initial trials suggested that ...chipmunks preferred the low tannin, white oak (W; Quercus alba) acorns over the high tannin, red oak acorn (R, Q. rubra). However, the smaller size of the W acorns, and therefore greater ease of handling, possibly confounded the affects of tannin content on acorn choice. Additional field and laboratory experiments confirmed that chipmunks preferred smaller acorns, but W acorns were still preferred to equal-sized R acorns. Frequency of live capture of chipmunks during the period of acorn drop (mid-September to mid-November) at the field site was related directly to the total basal area (P = 0.02) but not number of W trees. Capture frequency was also correlated negatively with the number (P = 0.04) but not basal area of R trees in the canopy. Our results suggest that chipmunks prefer to eat W acorns and that chipmunk activity is in part influenced by this preference. Heavy chipmunk harvesting of the preferred W acorns may be influencing the successional patterns in the forest at our study site.
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