Kevin K. McCully

Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure.

Background The purpose of this study was to investigate the prevalence of skeletal muscle atrophy and its relation to exercise intolerance and abnormal muscle metabolism in patients with heart failure (HF). Methods and Results Peak Vo2, percent ideal body weight (% IBW), 24-hour urine creatinine (Cr), and anthropometrics were measured in 62 ambulatory patients with HF. 31P magnetic resonance spectroscopy (MRS) and imaging (MRI) of the calf were performed in 15 patients with HF and 10 control subjects. Inorganic phosphorus (Pi), phosphocreatine (PCr), and intracellular pH were measured at rest and during exercise. Calf muscle volume was determined from the sum of the integrated area of muscle in 1-cm-thick contiguous axial images from the patella to the calcaneus. A reduced skeletal muscle mass was noted in 68% of patients, as evidenced by a decrease in Cr-to-height ratio of <7.4 mg/cm and/or upper arm circumference of <5% of normal. Calf muscle volume (MRI) was also reduced in the patients with HF (controls, 675±84 cm3/m2; HF, 567±112 cm3/m2; p < 0.05). Fat stores were largely perserved with triceps skinfold of <5% of normal and/or IBW of <80% in only 8% of patients. Modest linear correlations were observed between peak Vo2 and both calf muscle volume per meter squared (r = 0.48) and midarm muscle area (r = 0.36) (both p < 0.05). 31P metabolic abnormalities during exercise were observed in the patients with HF, which is consistent with intrinsic oxidative abnormalities. The metabolic changes were weakly correlated with muscle volume (r = −0.42, p<0.05). Conclusions These findings indicate that patients with chronic HF frequently develop significant skeletal muscle atrophy and metabolic abnormalities. Atrophy contributes modestly to both the reduced exercise capacity and altered muscle metabolism.

Time-resolved spectroscopy of hemoglobin and myoglobin in resting and ischemic muscle.

Difficulties of quantitation of hemoglobin/myoglobin absorption changes in muscle have led to the development of a new approach using short pulses of light. This method uses input light pulses sufficiently short so that the time course of travel of light through the brain can be precisely measured. The time of arrival of light at the detector gives the optical path length, given the velocity of light in tissues. The intensity profile of photon migration in tissues permits determination of the path length that the exiting photons have traveled and the concentration change of the pigments. A cavity-dumped liquid dye laser illuminates the tissue with 130-ps pulses detected as 600-ps duration at a half height at 3.0-cm distance from the input point. The decay of intensity from the 50% point onward to 0.1% follows a logarithmic function of slope mu which is attributed to the total absorption coefficient of the tissue. Increments of mu due to deoxyhemoglobin absorption at 760 and 630 nm are used to calculate the concentration change. This permits the calculation of the path length for continuous light measurements of 2 cm for a particular geometry. Variation of the wavelength of the laser affords determination of a spectrum of changes in the tissue.

Noninvasive detection of skeletal muscle underperfusion with near-infrared spectroscopy in patients with heart failure.

The present study was undertaken to determine whether near-infrared spectroscopy can be used to noninvasively assess skeletal muscle oxygenation in patients with heart failure. The difference between light absorption at 760 and 800 nm was used to assess hemoglobin-myoglobin oxygenation. Initial studies conducted in isolated canine gracilis muscle demonstrated that 760-800-nm absorption correlated closely (r = -0.97 +/- 0.01) with venous hemoglobin O2 saturation when the muscle was stimulated to contract at 0.25-5.0 Hz. In normal subjects (n = 6) and patients with heart failure (n = 8), 760-800-nm absorption changes from the vastus lateralis muscle were monitored at rest, during progressive maximal bicycle exercise, and during thigh cuff inflation to suprasystolic pressure, an intervention designed to assess minimal hemoglobin-myoglobin oxygenation. Absorption changes were expressed relative to the full physiologic range noted from rest to thigh cuff inflation. During exercise, normal subjects exhibited an initial increase in hemoglobin-myoglobin oxygenation followed by a progressive decrease in oxygenation to 27 +/- 13% of the physiologic range at the peak exercise workload of 140 +/- 9 W. In contrast, patients exhibited an initial decrease in hemoglobin-myoglobin oxygenation with the first workload, followed by a progressive further decrease to 26 +/- 13% of the physiologic range at a peak exercise workload of 60 +/- 8 W, less than half the peak workload noted in the normal subjects. At all exercise loads, hemoglobin-myoglobin oxygenation was significantly less in the patients than in the normal subjects. These data suggest that near-infrared spectroscopy can detect impaired skeletal muscle O2 delivery in patients with heart failure. This technique could provide a valuable method of assessing muscle O2 delivery in patients, particularly before and after therapeutic interventions.

Near-infrared spectroscopy/imaging for monitoring muscle oxygenation and oxidative metabolism in healthy and diseased humans

Near-infrared spectroscopy (NIRS) was initiated in 1977 by Jobsis as a simple, noninvasive method for measuring the presence of oxygen in muscle and other tissues in vivo. This review honoring Jobsis highlights the progress that has been made in developing and adapting NIRS and NIR imaging (NIRI) technologies for evaluating skeletal muscle O(2) dynamics and oxidative energy metabolism. Development of NIRS/NIRI technologies has included novel approaches to quantification of the signal, as well as the addition of multiple source detector pairs for imaging. Adaptation of NIRS technology has focused on the validity and reliability of NIRS measurements. NIRS measurements have been extended to resting, ischemic, localized exercise, and whole body exercise conditions. In addition, NIRS technology has been applied to the study of a number of chronic health conditions, including patients with chronic heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, varying muscle diseases, spinal cord injury, and renal failure. As NIRS technology continues to evolve, the study of skeletal muscle function with NIRS first illuminated by Jobsis continues to be bright.

Effects of incremental exercise on cerebral oxygenation measured by near-infrared spectroscopy: A systematic review

We conducted a systematic review and meta-regression analysis to quantify effects of exercise on brain hemodynamics measured by near-infrared spectroscopy (NIRS). The results indicate that acute incremental exercise (categorized relative to aerobic capacity (VO(2)peak) as low - <30% VO(2)peak; moderate - ≥30% VO(2)peak to <60% VO(2)peak; hard - ≥60% VO(2)peak to <VO(2)peak; and very hard - ≥VO(2)peak intensities) performed by 291 healthy people in 21 studies is accompanied by moderate-to-large increases (mean effect, dz±95% CI) in the prefrontal cortex of oxygenated hemoglobin (O(2)Hb) or other measures of oxygen level (O(2)Hbdiff) or saturation (SCO(2)) (0.92±0.67, 1.17), deoxygenated hemoglobin (dHb) (0.87±0.56, 1.19), and blood volume estimated by total hemoglobin (tHb) (1.21±0.84, 1.59). After peaking at hard intensities, cerebral oxygen levels dropped during very hard intensities. People who were aerobically trained attained higher levels of cortical oxygen, dHb, and tHb than untrained people during very hard intensities. Among untrained people, a marked drop in oxygen levels and a small increase in dHb at very hard intensities accompanied declines in tHb, implying reduced blood flow. In 6 studies of 222 patients with heart or lung conditions, oxygenation and dHb were lowered or unchanged during exercise compared to baseline. In conclusion, prefrontal oxygenation measured with NIRS in healthy people showed a quadratic response to incremental exercise, rising between moderate and hard intensities, then falling at very hard intensities. Training status influenced the responses. While methodological improvements in measures of brain oxygen are forthcoming, these results extend the evidence relevant to existing models of central limitations to maximal exercise.

Vascular remodeling after spinal cord injury.

PURPOSE Our purpose was to determine whether spinal cord injured (SCI) subjects have decreased femoral artery diameter and maximal hyperemic blood flow when expressed per unit of muscle volume compared with able-bodied (AB) individuals. A secondary purpose was to determine whether blood flow recovery rates were similar between groups. METHODS Blood flow was measured in the femoral artery using Doppler ultrasound after distal thigh cuff occlusion of 4 and 10 min. Muscle mass of the lower leg was determined by magnetic resonance imaging (MRI). RESULTS SCI individuals had smaller muscle cross-sectional areas (37%, P = 0.001) and volumes (38%, P = 0.001) than AB individuals. Furthermore, femoral artery diameter (0.76 +/- 0.14 vs 0.48 +/- 0.06 cm, AB vs SCI, P < 0.001) and femoral artery maximal blood flow (2050 +/- 520 vs 1220 +/- 240 mL x min-1, AB vs SCI, P < 0.001) were lower in SCI than AB individuals. Femoral artery diameter and maximal blood flow per unit muscle volume did not differ between SCI and AB individuals (P = 0.418 and P = 0.891, respectively). Blood flow recovery after ischemia was prolonged in SCI compared with AB individuals for both cuff durations (P = 0.048). CONCLUSIONS In summary, femoral artery diameter and maximal hyperemic blood flow response per unit muscle volume are not different between SCI and AB individuals. Vascular atrophy after SCI appears to be closely linked to muscle atrophy. Furthermore, the SCI compared with AB individuals had a prolonged time to recovery, which may suggest decreased vessel reactivity.

The use of muscle near-infrared spectroscopy in sport, health and medical sciences: recent developments.

Near-infrared spectroscopy (NIRS) has been shown to be one of the tools that can measure oxygenation in muscle and other tissues in vivo. This review paper highlights the progress, specifically in this decade, that has been made for evaluating skeletal muscle oxygenation and oxidative energy metabolism in sport, health and clinical sciences. Development of NIRS technologies has focused on improving quantification of the signal using multiple wavelengths to solve for absorption and scattering coefficients, multiple pathlengths to correct for the influence of superficial skin and fat, and time-resolved and phase-modulated light sources to determine optical pathlengths. In addition, advances in optical imaging with multiple source and detector pairs as well as portability using small wireless detectors have expanded the usefulness of the devices. NIRS measurements have provided information on oxidative metabolism in various athletes during localized exercise and whole-body exercise, as well as training-induced adaptations. Furthermore, NIRS technology has been used in the study of a number of chronic health conditions. Future developments of NIRS technology will include enhancing signal quantification. In addition, advances in NIRS imaging and portability promise to transform how measurements of oxygen utilization are obtained in the future.

Injuries during the one repetition maximum assessment in the elderly

PURPOSE A decrease in strength, and its associated loss of functional ability is common among the elderly. Although resistance training can reverse this decline, associated injuries with frequently used strength assessments may present a greater risk. METHODS To evaluate the injuries associated with maximal strength evaluations, 83 relatively healthy elderly subjects (40 men and 43 women, 65.8 +/- 6.2 years) with and without prior weight training experience performed 1 repetition maximum testing (1 RM) involving 5 different exercises: chest press, leg extension, abdominal curl, arm curl, and seated calf raise. Subjects were separated into three groups depending on weight training experience, Group 1 had no weight training experience (n = 32), Group 2 had < 6 months of training (n = 24), and Group 3 had > 6 months of training (n = 27). Injury assessment was made 30 minutes, 2 days, and 7 days posttesting. RESULTS Two Group 1 subjects sustained an injury (2.4% of total subjects, 8% of Group 1). Eighty-one subjects safely completed the 1 RM assessment without injury (97.6% of total). Forty-eight of the 83 subjects complained of muscle soreness after testing (58% of total). This complaint alone was not sufficient to be categorized as an injury. CONCLUSIONS These results indicate that 1 RM testing is an acceptable tool in strength evaluations in the elderly. Additional precautions may be needed in inexperienced, elderly individuals to prevent injury.

Reduced oxidative muscle metabolism in chronic fatigue syndrome

The purpose of this study was to determine if chronic fatigue syndrome (CSF) is characterized by abnormalities in oxidative muscle metabolism. Patients with CFS according to Centers for Disease Control (CDC) criteria (n = 22) were compared to normal sedentary subjects (n = 15). CFS patients were also tested before and 2 days after a maximal treadmill test. Muscle oxidative capacity was measured as the maximal rate of postexercise phosphocreatine (PCr) resynthesis using the ADP model (Vmax) in the calf muscles using 31P magnetic resonance spectroscopy. Vmax was significantly reduced in CFS patients (39.6 ± 2.8 mmol/L/min, mean ± SE) compared to controls (53.8 ± 2.8 mmol/L/min). Two days postexercise there was no change in resting inorganic phosphate (Pi)/PCr or Vmax in the CFS patients (n = 14). In conclusion, oxidative metabolism is reduced in CFS patients compared to sedentary controls. In addition, a single bout of strenuous exercise did not cause a further reduction in oxidative metabolism, or alter resting Pi/PCr ratios.

Dietary quercetin supplementation is not ergogenic in untrained men

Quercetin supplementation increases muscle oxidative capacity and endurance in mice, but its ergogenic effect in humans has not been established. Our study investigates the effects of short-duration chronic quercetin supplementation on muscle oxidative capacity; metabolic, perceptual, and neuromuscular determinants of performance in prolonged exercise; and cycling performance in untrained men. Using a double-blind, pretest-posttest control group design, 30 recreationally active, but not endurance-trained, young men were randomly assigned to quercetin and placebo groups. A noninvasive measure of muscle oxidative capacity (phosphocreatine recovery rate using magnetic resonance spectroscopy), peak oxygen uptake (Vo(2peak)), metabolic and perceptual responses to submaximal exercise, work performed on a 10-min maximal-effort cycling test following the submaximal cycling, and voluntary and electrically evoked strength loss following cycling were measured before and after 7-16 days of supplementation with 1 g/day of quercetin in a sports hydration beverage or a placebo beverage. Pretreatment-to-posttreatment changes in phosphocreatine recovery time constant, Vo(2peak,) substrate utilization, and perception of effort during submaximal exercise, total work done during the 10-min maximal effort cycling trial, and voluntary and electrically evoked strength loss were not significantly different (P > 0.05) in the quercetin and placebo groups. Short duration, chronic dietary quercetin supplementation in untrained men does not improve muscle oxidative capacity; metabolic, neuromuscular and perceptual determinants of performance in prolonged exercise; or cycling performance. The null findings indicate that metabolic and physical performance consequences of quercetin supplementation observed in mice should not be generalized to humans.