Electrical stimulation-evoked resistance exercise therapy improves arterial health after chronic spinal cord injury.

STUDY DESIGN: Repeated measures training intervention. OBJECTIVES: To evaluate the effects of neuromuscular electrical stimulation (NMES)-induced resistance exercise therapy on lower extremity arterial health in individuals with chronic, complete spinal cord injury (SCI). We define "arterial health" using three surrogate markers: (a) resting diameter, (b) flow-mediated dilation (FMD), and (c) arterial range. SETTING: Department of Kinesiology, University of Georgia, USA. METHODS: We assessed five 36+/-5-year-old male individuals with chronic, complete SCI before, during, and after 18 weeks of training. The quadriceps femoris muscle group of both legs were trained twice a week with 4 x 10 repetitions of unilateral, dynamic knee extensions. The health of the posterior tibial artery was assessed using a B-mode ultrasound unit equipped with a high-resolution video capture device. Proximal occlusion was used to evoke ischemia for 5 min and then for 10 min. FMD was calculated using the peak diameter change (above rest) following 5 min occlusion. Arterial range was calculated using minimum (during occlusion) and maximum diameters (post 10 min occlusion). Hierarchical linear modeling accounted for the nested (repeated measures) experimental design. RESULTS: FMD improved from 0.08+/-0.11 mm (2.7%) to 0.18+/-0.15 mm (6.6%) (P=0.004), and arterial range improved from 0.36+/-0.28 to 0.94+/-0.40 mm (P=0.001), after 18 weeks of training. Resting diameter did not significantly change. CONCLUSIONS: Home-based, self-administered NMES resistance exercise therapy consisting of 80 contractions/week improved FMD and arterial range. This provides evidence that resistance exercise therapy can improve arterial health after SCI, which may reduce the risk of future cardiovascular disease.

Electrically stimulated resistance training in SCI individuals increases muscle fatigue resistance but not femoral artery size or blood flow.

STUDY DESIGN: Longitudinal. OBJECTIVES: The purpose of this study was to evaluate the effect of lower extremity resistance training on quadriceps fatigability, femoral artery diameter, and femoral artery blood flow. SETTING: Academic Institution. METHODS: Five male chronic spinal cord injury (SCI) individuals (American Spinal Injury Association (ASIA): A complete; C5-T10; 36+/-5 years old) completed 18 weeks of home-based neuromuscular electrical stimulation (NMES) resistance training. Subjects trained the quadriceps muscle group twice a week with four sets of 10 dynamic knee extensions against resistance while in a seated position. All measurements were made before training and after 8, 12, and 18 weeks of training. Ultrasound was used to measure femoral artery diameter and blood flow. Blood flow was measured before and after 5 and 10 min of distal cuff occlusion, and during a 4-min isometric electrical stimulation fatigue protocol. RESULTS: Training resulted in significant increases in weight lifted and muscle mass, as well as a 60% reduction in muscle fatigue (P = 0.001). However, femoral arterial diameter did not increase. The range was 0.44+/-0.03 to 0.46+/-0.05 cm over the four time points (P = 0.70). Resting, reactive hyperemic, and exercise blood flow did not appear to change with training. CONCLUSION: NMES resistance training improved muscle size and fatigue despite an absence of response in the supplying vasculature. These results suggest that the decreases in arterial caliber and blood flow seen with SCI are not tightly linked to muscle mass and fatigue resistance. In addition, muscle fatigue in SCI patients can be improved without increases in arterial diameter or blood flow capacity.

Oxygen transport and intracellular bioenergetics on stimulated cat skeletal muscle.

A unique multiparameter recording of skeletal muscle bioenergetics, biochemistry and biomechanics has permitted determination of novel relationships among hemodynamics, cellular high-energy metabolites and mitochondrial bioenergetics in feline skeletal muscle. The study utilizes 31P NMR, NIR, and NADH fluorescence spectrophotometry, biochemical assays and muscle performance. Seven cats were anesthetized and mechanically ventilated. Calf muscles were stimulated through sciatic nerve electrical stimulation and tension was monitored by a strain gauge connected to the Achilles tendon. We stimulated the muscle to produce several workloads up to Vmax. We also changed FiO2 from normoxia to hypoxia for each %Vmax. From these results, the most sensitive indicators of cellular hypoxia leading to a reduction in muscle performance can be determined. Hemoglobin deoxygenation generally does not correlate with cellular hypoxia, although when the HbO2 drops below 30% saturation there is an increased incidence of cellular hypoxia. The [ADP], which is known to regulate mitochondrial function, has a close relation to the work, not to the hypoxia. On the other hand, the mitochondrial NADH does respond to cellular PO2. The degree of oxidation (NADH decrease) due to the ATP flux shifts with oxygen availability in mild to moderate hypoxia (at FiO2 down to 9%). As cellular hypoxia causes decreases in muscle performance (moderate to severe hypoxia), NADH is being reduced rather than oxidized with increasing workloads.

Blood flow response in individuals with incomplete spinal cord injuries.

STUDY DESIGN: Cross sectional comparison, control group. OBJECTIVE: To determine if incomplete spinal cord injured patients (SCI) have an abnormal blood flow response to cuff ischemia compared to able-bodied individuals (AB). SETTING: Academic institution. METHODS: Blood flow in five chronic incomplete SCI patients (C4-C5) and 17 able bodied individuals was measured in the common femoral artery using quantitative Doppler ultrasound (GE LogiQ 400CL) at rest and after distal thigh cuff occlusion of 2, 4 and 10 min to investigate whether blood flow or vascular control were different in SCI's and AB. RESULTS: Blood flow and the diameter of the common femoral artery at rest were similar in incomplete SCI and AB. Peak flow after 10 min of cuff ischemia (the highest found) was also comparable between incomplete SCI and AB. The half-time for recovery of blood flow to baseline after 2, 4 or 10 min of ischemia was 50% longer for incomplete SCI compared to the AB (P = 0.023). In addition, peak blood flow after 2 and 4 min of ischemia relative to the maximum, 10 min value (2/10 and 4/10 ratios) was lower in incomplete SCI compared to AB (0.65 +/- 0.06 vs 0.76 +/- 0.15, P = 0.029 and 0.75 +/- 0.10 vs 0.89 +/- 0.11, P = 0.014, respectively). CONCLUSION: This study demonstrated that incomplete spinal cord injured patients have impaired vascular control seen as a slower return to resting flow after cuff ischemia and reduced sensitivity to ischemia relative to maximum flow. However, incomplete SCI patients did not demonstrate impaired flow capacity as seen in complete SCI patients suggesting that smaller cardiovascular abnormalities are seen with incomplete versus complete SCI injury. Impaired vascular control may serve to limit exercise capacity and may contribute to increased cardiovascular disease. Impaired circulation could contribute to impaired muscle function and poor cardiovascular health in incomplete SCI's, although these findings need to be replicated in a study with more subjects.

Regional difference of muscle oxygen saturation and blood volume during exercise determined by near infrared imaging device.

UNLABELLED: Using a near infrared (NIR) imaging device, we tested the hypothesis that regional differences in oxygen status could be detected in the gastrocnemius muscle during exercise and recovery. Six healthy subjects performed the standing plantar flexion exercises for 2 min; the frequency was one contraction per second. The NIR imaging device was placed over the medial head of the right gastrocnemius muscle and the signals from two optical sensors situated on the middle proximal and middle distal portions were used. The NIR-O(2) saturation (difference between deoxygenated and oxygenated Hb signals) and NIR-blood volume (sum of the oxygenated and deoxygenated Hb signals) were calculated in optical density units. Plantar flexion resulted in more deoxygenation during exercise and more reoxygenation during recovery in the distal portion compared with the proximal portion. The changes in NIR-O(2) between rest and a 2 min exercise, and between a 2 min exercise and a 3 min recovery were 0.11 and -0.23, respectively, in the distal portion, which were significantly larger than proximal values (0.05 and -0.10, p < 0.05). Plantar flexion resulted in lower NIR-blood volumes during exercise and greater recovery of blood after exercise in the distal portion compared with the proximal portion. The changes in NIR blood volume between rest and a 2 min exercise and between a 2 min exercise and a 3 min recovery were -0.19 and 0.31, respectively, in the distal portion, significantly larger than proximal values (-0.07 and 0.12, p < 0.05 for all comparisons). These findings indicate that the distal portion of the medial gastrocnemius had larger changes in NIR-O(2) saturation and NIR-blood volume than the proximal portion had. This is consistent with the distal portion having a greater impairment of blood flow possibly because of the higher intramuscular pressure during exercise. IN CONCLUSION: (1) regional differences in oxygen status in the gastrocnemius muscle were detected with exercise, with the distal portion having greater NIR-O(2) saturation and NIR-blood volume changes, and (2) the NIR imaging device might be a useful method to detect the regional differences of oxygen status in the muscle.

Near-infrared spectroscopy: what can it tell us about oxygen saturation in skeletal muscle?

Near-infrared spectroscopy (NIRS) measures hemoglobin saturation in small vessels. A number of interesting studies have used this method. However, difficulties with signal quantification and studies in which NIRS oxygen saturation did not behave as expected raise concerns. NIRS remains promising for studies of skeletal muscle, but a better understanding of the method is needed.

A reappraisal of the role of chlorambucil in patients with end stage ovarian cancer who have previously been treated with platinum regimens.

The role of chlorambucil in end stage platinum resistant epithelial ovarian cancer was evaluated in women with end stage ovarian cancer. They had received platinum based chemotherapy and all other intravenous chemotherapeutic options had been exhausted. Over a 15 year period, 30 patients were identified. The median age was 64.5 years (range 45-81). The median number of chlorambucil pulses was 4 (range 1-16). The median survival following the introduction of chlorambucil was 5.5 months (range 0.72-38.8). The 22 patients who survived for longer than three months were significantly younger than those who did not (p = 0.03). Apart from two patients who developed transient myelosupression there were no toxic side effects. Chlorambucil should be considered as a therapeutic option in end stage ovarian cancer. It is has minimal toxicity, and can be prescribed safely for long term use. In younger women, an increase in benefit may be anticipated.

Nuclear magnetic resonance spectroscopy: its role in providing valuable insight into diverse clinical problems.

Skeletal muscle plays an important role in respiratory and cardiovascular physiology. The ability to measure metabolic changes in skeletal muscle has been enhanced with the advent of magnetic resonance spectroscopy (MRS). MRS measurements have been used to understand the metabolic control of respiration and to evaluate metabolic changes in the muscle in patients with respiratory and cardiac diseases. The key to the respiratory control measurements is the ability to measure intracellular pH with MRS. Muscle oxidative metabolism has been measured in two ways: during steady-state exercise and using recovery kinetics. The similarities in the metabolic findings for pulmonary and coronary disease suggest the potential for some interesting common pathways.

Impaired oxygen delivery to muscle in chronic fatigue syndrome.

The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced oxygen delivery to muscles. Patients with CFS according to CDC (Center for Disease Control) criteria (n=20) were compared with normal sedentary subjects (n=12). Muscle oxygen delivery was measured as the rate of post-exercise and post-ischaemia oxygen-haem resaturation. Oxygen-haem resaturation was measured in the medial gastrocnemius muscle using continuous-wavelength near-IR spectroscopy. Phosphocreatine resynthesis was measured simultaneously using (31)P magnetic resonance spectroscopy. The time constant of oxygen delivery was significantly reduced in CFS patients after exercise (46.5+/-16 s; mean+/-S.D.) compared with that in controls (29.4+/-6.9 s). The time constant of oxygen delivery was also reduced (20.0+/-12 s) compared with controls (12.0+/-2.8 s) after cuff ischaemia. Oxidative metabolism was also reduced by 20% in CFS patients, and a significant correlation was found between oxidative metabolism and recovery of oxygen delivery. In conclusion, oxygen delivery was reduced in CFS patients compared with that in sedentary controls. This result is consistent with previous studies showing abnormal autonomic control of blood flow. Reduced oxidative delivery in CFS patients could be specifically related to CFS, or could be a non-specific effect of reduced activity levels in these patients. While these results suggest that reduced oxygen delivery could result in reduced oxidative metabolism and muscle fatigue, further studies will be needed to address this issue.

The effects of peripheral vascular disease on gait.

This study was designed to determine whether patients with peripheral vascular disease (PVD) have gait abnormalities. A previous study on humans with PVD found no abnormalities whereas significant gait changes were seen with a rat model of PVD. The study population was comprised of 10 controls and 9 subjects with PVD (all male). The PVD group had documented pain in one or both legs while walking. Subjects ranged in age from 55-92 years of age, with a mean age of 69 in the PVD group and 70 in the control group. The GaitMat II system was used to measure both spatial and temporal variables of gait. Subjects walked across the mat, four to six times, at their comfortable walking speed. The PVD group then walked on a treadmill until they experienced moderate claudication pain and felt they had to stop (pain levels between 6 and 8, with maximal pain at level 10). Control group walked on a treadmill for 10 minutes without pain. All subjects repeated the gait tests on the GaitMat H system immediately after treadmill walking. Claudication pain persisted in the PVD group during the second gait test. The PVD group was not different than control group in any of the measured variables on the first test (p values from .35 to .99). Difference scores (post- minus pre-treadmill walking)for PVD group were significantly different than those for control group on 8 of 11 variables (p values <.005). The primary response in PVD subjects was reduced walking speed (1.02+/-0.16 to 0.94+/-0.16 m/s) and reduced step length (0.60+/-0.08 to 0.57+/-0.09 m/s), whereas control subjects increased their speed (1.09+/-0.17 to 1.19+/-0.19 m/s) and step length (0.63+/-0.10 to 0.67+/-0.10 m/s). No asymmetries in gait were measured in either group, either before or after treadmill walking. In conclusion, PVD subjects were not different in gait while rested, but responded to claudication pain by reducing preferred walking speed and step size.

In vivo determination of altered hemoglobin saturation in dogs with M-type phosphofructokinase deficiency.

Muscle-type phosphofructokinase (M-PFK) deficiency causes an exertional myopathy and chronic hemolysis in affected humans and dogs, the only animal model available. Deficient individuals have impaired glycolytic metabolism, impaired oxidative metabolism, and increased hemoglobin-oxygen (HbO2) affinity as a result of low 2,3-diphosphoglycerate (2,3-DPG) levels. The purpose of this study was to determine if PFK-deficient muscle has abnormal oxygen saturation during exercise. Oxygen saturation of hemoglobin/myoglobin was measured noninvasively in skeletal muscle during progressive muscle activation using near-infrared spectroscopy (NIRS). Muscle metabolites were also measured using magnetic resonance spectroscopy (MRS). PFK-deficient and normal dogs were anesthetized and the cranial tibial muscles stimulated for 6 min at each of four different rates (1, 2, 4, and 8 Hz). With increasing stimulation, muscles from normal dogs showed progressive decrease in hemoglobin saturation. In contrast, PFK-deficient dogs exhibited either an increase in hemoglobin saturation or an initial decrease with no further change. PFK-deficient muscles accumulated 11.1 +/- 3.5 mmol/L of sugar phosphate which was not seen in normal muscle and had higher calculated [ADP] levels at each stimulation level, indicating impaired oxidative metabolism. These findings are consistent with the hypothesis that these animals have impaired oxidative metabolism and impaired muscle O2 extraction from hemoglobin due to increased HbO2 affinity. NIRS appears to be a useful noninvasive method of monitoring tissue oxygen saturation in normal or disease conditions.

The effects of high-intensity and low-intensity cycle ergometry in older adults with knee osteoarthritis.

BACKGROUND: People with osteoarthritis (OA) of the knee experience pain and deconditioning that lead to disability. This study challenged the clinical belief that repetitive lower extremity exercise is not indicated in persons with knee OA. The effects of high-intensity and low-intensity stationary cycling on functional status, gait, overall and acute pain, and aerobic capacity were examined. METHODS: Thirty-nine adults (71+/-6.9 years old) with complaints of knee pain and diagnosis of OA were randomized to either a high-intensity (70% heart rate reserve [HRR]) or low-intensity (40% HRR) exercise group for 10 weeks of stationary cycling. Participants cycled for 25 minutes, 3 times per week. Before and after the exercise intervention they completed the Arthritis Impact Measurement Scale 2 for overall pain assessment, underwent timed chair rise, 6-minute walk test, gait, and graded exercise treadmill tests. Acute pain was reported daily with a visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index scale. RESULTS: Analysis of variance revealed that participants in both groups significantly improved in the timed chair rise, in the 6-minute walk test, in the range of walking speeds, in the amount of overall pain relief, and in aerobic capacity. No differences between groups were found. Daily pain reports suggested that cycling did not increase acute pain in either group. CONCLUSIONS: Cycling may be considered as an alternative exercise modality for patients with knee OA. Low-intensity cycling was as effective as high-intensity cycling in improving function and gait, decreasing pain, and increasing aerobic capacity.

Identification of peripheral vascular disease in elderly subjects using optical spectroscopy.

The purpose of this study was to determine the usefulness of near-infrared spectroscopy (NIRS) measurements to identify peripheral vascular disease (PVD). Usefulness was determined by the frequency of a successful test, as well as comparison with standard clinical assessments. Study subjects (N = 117, mean age = 67.8 +/- 8.1 yrs) responded to a free screening for PVD. NIRS was used to measure the relative O2 saturation of hemoglobin in the soleus muscle. The time to 1/2 recovery of O2 saturation (O2T1/2) was measured after 1 minute of repeated plantar flexions using a Cybex Eagle seated calf machine. O2T1/2 was used as many subjects had recovery curves that did not have an exponential line shape. The test was done on both legs and the worst leg was used for analysis. For comparative purposes, a clinical history and physical examination were performed by a physician or nurse practitioner, which included questions on intermittent claudication, examination of peripheral pulses, and questions to identify cardiovascular risk factors. NIRS signals were obtained on 105 of 117 subjects (89% success rate). Subjects with body mass index (BMI) values above 32 appeared to have NIRS O2T1/2 values that were less reliable than subjects with BMI values < or = 32 (77% success rate). The O2T1/2 was longer in subjects with claudication and reduced pulses than in subjects without these conditions. Sensitivity comparing O2T1/2 to claudication and reduced pulse varied from 51-76% and specificity from 65-80%, depending on the cutoff value for O2T1/2 that was used (normal value plus 1 or 2 SD). A longer O2T1/2 was significantly associated with incidence of diabetes, smoking, hypercholesterol, and coronary bypass surgery. In summary, successful NIRS O2T1/2 measurements were made in 77% of the subjects, with failure primarily occurring in obese subjects. NIRS O2T1/2 measurements showed reasonable although not strong agreements with clinical assessment of PVD, and with some risk factors for cardiovascular disease.

Noninvasive measurement of phosphocreatine recovery kinetics in single human muscles.

The rate at which phosphocreatine (PCr) is resynthesized after exercise is related to muscle oxidative capacity (Vmax). With the use of a one-dimensional image-guided, localized nuclear magnetic resonance spectroscopy technique, PCr kinetics were monitored in the medial gastrocnemius of eight healthy subjects after voluntary, short duration, maximal rate exercise. Localized spectra were obtained every 6 s with <5% contamination from nonselected regions. Maximal rate exercise elicited near-maximal to maximal muscle activation, as indicated by the high-PCr hydrolysis rate (2.26 +/- 0.07 mM/s) and extensive PCr depletion. At the end of 9 s of maximal rate exercise, PCr was depleted by 61.4 +/- 2.4% and intracellular pH was 7.04 +/- 0.03. After 9 s of maximal rate exercise, PCr recovered with a rate constant (kPCr) of 1.87 +/- 0.15 min(-1) and a Vmax of 67.2 +/- 6.0 mM/min. Independent of prior activity, aerobic ATP synthesis rates reached 48.6 +/- 4.9 mM/min within 9 s. Extending maximal rate exercise to 30 s resulted in 92.0 +/- 1.2% PCr depletion and an intracellular pH of 6.45 +/- 0.07. The intracellular acidosis separated the direct relationship between kPCr and muscle Vmax but did not affect the initial PCr resynthesis rate.

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.

Long-term survival in a patient with verrucous carcinoma of the esophagus.

A 66-yr-old white male with a long-standing history of gastroesophageal reflux and Barrett's esophagus developed squamous cell dysplasia proximal to the site of the metaplastic epithelium. Two months later, he presented with progressive dysphagia. Upper endoscopy revealed near obliteration of the lumen from a large friable mass in the distal esophagus. Repeat endoscopic biopsies revealed areas of focal dysplasia but were inconclusive for the presence of malignancy. At surgery, a large inflammatory fibrotic mass was resected that was confirmed histologically to be a verrucous squamous cell carcinoma. Twenty-two months after the resection, there is no evidence of tumor recurrence. The case and relevant literature is discussed.