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Near-infrared spectrometry (NIRS) is a well-known method used to measure in vivo tissue oxygenation and hemodynamics. This method is used to derive relative measures of hemoglobin (Hb) + myoglobin (Mb) oxygenation and total Hb (tHb) accumulation from measurements of optical attenuation at discrete wavelengths. We present the design and validation of a new NIRS oxygenation analyzer for the measurement of muscle oxygenation kinetics. This design optimizes optical sensitivity and detector wavelength flexibility while minimizing component and construction costs. Using in vitro validations, we demonstrate 1) general optical linearity, 2) system stability, and 3) measurement accuracy for isolated Hb. Using in vivo validations, we demonstrate 1) expected oxygenation changes during ischemia and reactive hyperemia, 2) expected oxygenation changes during muscle exercise, 3) a close correlation between changes in oxyhemoglobin and oxymyoglobin and changes in deoxyhemoglobin and deoxymyoglobin and limb volume by venous occlusion plethysmography, and 4) a minimal contribution from movement artifact on the detected signals. We also demonstrate the ability of this system to detect abnormal patterns of tissue oxygenation in a well-characterized patient with a deficiency of skeletal muscle coenzyme Q(10). We conclude that this is a valid system design for the precise, accurate, and sensitive detection of changes in bulk skeletal muscle oxygenation, can be constructed economically, and can be used diagnostically in patients with disorders of skeletal muscle energy metabolism.

Skeletal muscle can utilize many different substrates, and traditional methodologies allow only indirect discrimination between oxidative and nonoxidative uptake of substrate, possibly with contamination by metabolism of other internal organs. Our goal was to apply 1H- and 13C-nuclear magnetic resonance spectroscopy to monitor the patterns of [3-13C]lactate and [1,2-13C]acetate (model of simple carbohydrates and fats, respectively) utilization in resting vs. contracting muscle extracts of the isolated perfused rat hindquarter. Total metabolite concentrations were measured by using NADH-linked fluorometric assays. Fractional oxidation of [3-13C]lactate was unchanged by contraction despite vascular endogenous lactate accumulation. Although label accumulated in several citric acid cycle (CAC) intermediates, contraction did not increase the concentration of CAC intermediates in any muscle extracts. We conclude that 1) the isolated rat hindquarter is a viable, well-controlled model for measuring skeletal muscle 13C-labeled substrate utilization; 2) lactate is readily oxidized even during contractile activity; 3) entry and exit from the CAC, via oxidative and nonoxidative pathways, is a component of normal muscle metabolism and function; and 4) there are possible differences between gastrocnemius and soleus muscles in utilization of nonoxidative pathways.

The balance between carbohydrate and fatty acid utilization in skeletal muscle previously has been studied in vivo by using a variety of methods such as arteriovenous concentration differences and radioactive isotope tracer techniques. However, these methodologies provide only indirect estimates of substrate oxidation. We used 13C-nuclear magnetic resonance (NMR) spectroscopy and non-steady-state isotopomer analysis to directly quantify the relative oxidation of two competing exogenous substrates in rat skeletal muscles. We infused [1,2-13C]acetate and [3-13C]lactate intravenously in anesthetized rats during the final 30 min of 35 (n = 10) or 95 (n = 10) min of intense, unilateral, rhythmic hindlimb contractions. 13C-NMR spectroscopy and isotopomer analysis were performed on extracts of gastrocnemius and soleus muscles from both the contracting and contralateral resting hindlimbs. We found that 1) [13C]lactate and [13C]acetate were taken up and oxidized by both resting and contracting skeletal muscles; and 2) high-intensity muscle contractions altered the pattern of substrate utilization such that the relative oxidation of acetate decreased while that of lactate remained unchanged or increased. Based on these findings, we propose that 13C-NMR spectroscopy in combination with isotopomer analysis can be used to study the general dynamics of substrate competition between carbohydrates and fats in rat skeletal muscle.

Clinical evaluation of the locomotor system has long been hampered by difficulty in assessing the morphologic and functional integrity of skeletal muscles. Diagnostic imaging represents a major advance in the diagnosis and management of patients with locomotor dysfunction through the possibility of probing beyond overlying soft tissues to identify muscle lesions, determine their extent, characterize their composition, direct invasive procedures, and monitor therapies. Magnetic resonance imaging (MRI) appears to be the most promising of available imaging methods, because of its great sensitivity to changes in muscle water distribution and fat content. Also, it can distinguish between individual deep and superficial muscles. Serial evaluations of many muscles are practical because of the safety of MRI. While the cost effectiveness in the workup of locomotor dysfunction remains to be determined, the scientific and practical clinical information now available merits further investigation by clinicians and radiologists alike. The purpose of this review is to describe the potential role of skeletal muscle MRI in evaluating the locomotor system.

The effect of high-intensity exercise on the respiratory capacity of skeletal muscle was studied in horses which ran five 600-m bouts on a track with 2 min of rest between exercise bouts, or once to fatigue on a treadmill at an intensity that elicited the maximal oxygen uptake. Venous blood and biopsy samples of the middle gluteal muscle were collected at rest, after each exercise bout, and 30 and 60 min post-exercise. Blood samples were analyzed for lactate concentration and pH and muscle samples for metabolites, pH, and respiratory capacity. Venous blood and muscle pH declined to 6.91 +/- 0.02 and 6.57 +/- 0.02, respectively, after the fifth track run and to 6.98 +/- 0.02 and 6.71 +/- 0.07, respectively, after treadmill running. Muscle metabolite changes were consistent with the metabolic response to high-intensity exercise. Muscle respiratory capacity declined greater than 20% (P less than 0.05) after a single exercise bout and was 45% of the control value after the fifth track run. Tissue respiration was depressed 60 min post-exercise but was normal 24 h later. These observations suggest that high-intensity exercise impairs the respiratory capacity of the working muscle. Although this occurred in parallel with reductions in pH, other factors could be responsible for this response.

31P MR spectroscopic studies of forearm exercise frequently assume that the volume sampled is appropriate for the muscle of interest and that individual variations in muscle anatomy and use are not important. Postexercise MR imaging was used to assess variations in the size, location, and use of forearm flexors and the accuracy of palpation as a method for locating the muscle of interest. By using the information obtained with MR, the effects of errors in surface-coil position relative to the muscle of interest on 31P MR spectroscopy were examined. In the midforearm of seven men, the greatest diameter of the flexor carpi ulnaris was 29 +/- 4 mm, and that of the flexor digitorum superficialis was 28 +/- 6 mm. However, in the proximal forearm, 58 +/- 10% of the diameter was covered by the palmaris longus, when present (79% of subjects). An unexpected finding was that a focal portion of the superficial finger flexor was used primarily as a wrist flexor in 26% of subjects. Palpation incorrectly identified flexor muscle margins by more than 15 mm in 50% of attempts. When a surface coil was positioned over wrist flexors during handgrip, attenuation of exercise-induced changes in 31P spectra resulted. Exercise-enhanced MR imaging reveals variations in forearm muscle anatomy and use that are common and difficult to appreciate by palpation. It therefore allows improved localization of the sensitive volume for MR spectroscopic studies of muscle physiology.