Skeletal muscle chemoreflex and pHi in exercise ventilatory control

To determine whether skeletal muscle hydrogen ion mediates ventilatory drive in humans during exercise, 12 healthy subjects performed three bouts of isotonic submaximal quadriceps exercise on each of 2 days in a 1.5-T magnet for 31P-magnetic resonance spectroscopy (31P-MRS). Bilateral lower extremity positive pressure cuffs were inflated to 45 Torr during exercise (BLPPex) or recovery (BLPPrec) in a randomized order to accentuate a muscle chemoreflex. Simultaneous measurements were made of breath-by-breath expired gases and minute ventilation, arterialized venous blood, and by 31P-MRS of the vastus medialis, acquired from the average of 12 radio-frequency pulses at a repetition time of 2.5 s. With BLPPex, end-exercise minute ventilation was higher (53.3 +/- 3.8 vs. 37.3 +/- 2.2 l/min; P < 0.0001), arterialized PCO2 lower (33 +/- 1 vs. 36 +/- 1 Torr; P = 0.0009), and quadriceps intracellular pH (pHi) more acid (6.44 +/- 0.07 vs. 6.62 +/- 0.07; P = 0.004), compared with BLPPrec. Blood lactate was modestly increased with BLPPex but without a change in arterialized pH. For each subject, pHi was linearly related to minute ventilation during exercise but not to arterialized pH. These data suggest that skeletal muscle hydrogen ion contributes to the exercise ventilatory response.     

Skeletal muscle function and its relation to exercise tolerance in chronic heart failure

OBJECTIVES: This study sought to define the relation between muscle function and bulk in chronic heart failure (HF) and to explore the association between muscle function and bulk and exercise capacity. BACKGROUND: Skeletal muscle abnormalities have been postulated as determinants of exercise capacity in chronic HF. Previously, muscle function in chronic HF has been evaluated in relatively small numbers of patients and with variable results, with little account being taken of the effects of muscle wasting. METHODS: One hundred male patients with chronic HF and 31 healthy male control subjects were studied. They were matched for age (59.0 +/- 1.0 vs. 58.7 +/- 1.7 years [mean +/- SEM]) and body mass index (26.6 +/- 0.4 vs. 26.3 +/- 0.7 kg/m2). We assessed maximal treadmill oxygen consumption (VO2), quadriceps maximal isometric strength, fatigue (20-min protocol, expressed in baseline maximal strength) and computed tomographic cross-sectional area (CSA) at midthigh. RESULTS: Peak VO2 was lower in patients (18.0 +/- 0.6 vs. 33.3 +/- 1.4 ml/min per kg, p < 0.0001), although both groups achieved a similar respiratory exchange ratio at peak exercise (1.15 +/- 0.01 vs. 1.19 +/- 0.03, p = 0.13). Quadriceps (582 vs. 652 cm2, p < 0.05) and total leg muscle CSA (1,153 vs. 1,304 cm2, p < 0.005) were lower in patients with chronic HF. Patients were weaker than control subjects (357 +/- 12 vs. 434 +/- 18 N, p < 0.005) and also exhibited greater fatigue at 20 min (79.1% vs. 92.1% of baseline value, p < 0.0001). After correcting strength for quadriceps CSA, significant differences persisted (5.9 +/- 0.2 vs. 7.0 +/- 0.3 N/cm2, p < 0.005), indicating reduced strength per unit muscle. In patients, but not control subjects, muscle CSA significantly correlated with peak absolute VO2 (R = 0.66, p < 0.0001) and is an independent predictor of peak absolute VO2. CONCLUSIONS: Patients with chronic HF have reduced quadriceps maximal isometric strength. This weakness occurs as a result of both quantitative and qualitative abnormalities of the muscle. With increasing exercise limitation there is increasing muscle weakness. This progressive weakness occurs predominantly as a result of loss of quadriceps bulk. In patients, this muscular atrophy becomes a major determinant of exercise capacity.     

Skeletal muscle blood flow in humans and its regulation during exercise

Regional limb blood flow has been measured with dilution techniques (cardio-green or thermodilution) and ultrasound Doppler. When applied to the femoral artery and vein at rest and during dynamical exercise these methods give similar reproducible results. The blood flow in the femoral artery is approximately 0.3 L min(-1) at rest and increases linearly with dynamical knee-extensor exercise as a function of the power output to 6-10 L min[-1] (Q= 1.94 + 0.07 load). Considering the size of the knee-extensor muscles, perfusion during peak effort may amount to 2-3 L kg(-1) min(-1), i.e. approximately 100-fold elevation from rest. The onset of hyperaemia is very fast at the start of exercise with T 1/2 of 2-10 s related to the power output with the muscle pump bringing about the very first increase in blood flow. A steady level is reached within approximately 10-150 s of exercise. At all exercise intensities the blood flow fluctuates primarily due to the variation in intramuscular pressure, resulting in a phase shift with the pulse pressure as a superimposed minor influence. Among the many vasoactive compounds likely to contribute to the vasodilation after the first contraction adenosine is a primary candidate as it can be demonstrated to (1) cause a change in limb blood flow when infused i.a., that is similar in time and magnitude as observed in exercise, and (2) become elevated in the interstitial space (microdialysis technique) during exercise to levels inducing vasodilation. NO appears less likely since NOS blockade with L-NMMA causing a reduced blood flow at rest and during recovery, it has no effect during exercise. Muscle contraction causes with some delay (60 s) an elevation in muscle sympathetic nerve activity (MSNA), related to the exercise intensity. The compounds produced in the contracting muscle activating the group IIl-IV sensory nerves (the muscle reflex) are unknown. In small muscle group exercise an elevation in MSNA may not cause vasoconstriction (functional sympatholysis). The mechanism for functional sympatholysis is still unknown. However, when engaging a large fraction of the muscle mass more intensely during exercise, the MSNA has an important functional role in maintaining blood pressure by limiting blood flow also to exercising muscles.     

Skeletal muscle fiber type, resistance training, and strength-related performance

The research goal was to attempt to clarify the consequences of increased strength on performance at submaximal exercise intensities. Eight subjects (4 males, 4 females) completed a 3-d.wk-1, 16-wk resistance training regimen. After training, upper (bench press, BP) and lower (parallel squat, PS) extremity strength were increased by 23% and 37%, respectively. Performance at the same absolute work rates as before training was increased by 30-159% following training depending on intensity and type of exercise. Performance at the same relative work rates (80%, 60%, 40%) remained unchanged by the training for both exercises. Prior to training, PS repetitions at 40% were correlated (r = 0.69, P < 0.05) with the percentage of slow-twitch (ST) fibers in the vastus lateralis muscle. There were similar relationships at 40% (r = 0.73) and at 60% (r = 0.83) for the PS exercise after training. However, the resistance program did not result in greater relative submaximal performance in individuals with a higher percentage of ST fibers. We conclude that strength improvement of up to 40% does not produce a strength-related performance deficit, when training and testing procedures are identical. Yet, these data do not rule out the potential of a strength-related repetition performance deficit. When subjects were equally divided by strength levels, those tested at the highest absolute resistance had significantly lower bench press repetition performance at 60% and 40% of the 1-RM than the subjects tested at the lowest absolute resistance.     

Skeletal muscle mitochondrial myopathy as a cause of exercise intolerance in a horse

Although exertional myopathies are commonly recognized in horses, specific etiologies have not been identified. This is the first report in the horse of a deficiency of Complex I respiratory chain enzyme associated with profound exercise intolerance. Physical examination, routine blood tests, endoscopy, and ultrasonograms of the heart and iliac arteries were unremarkable. With slow, incremental exercise (speeds 1.5-7 m/s), the Arabian mare showed a marked lactic acidosis, increased mixed venous PVO2, and little change in oxygen consumption. Muscle biopsies contained large accumulations of mitochondria with bizarre cristae formations. Biochemical analyses revealed a very low activity of the first enzyme complex in the mitochondrial respiratory chain (NADH CoQ reductase). The exercise intolerance and muscle stiffness in this horse were attributed to a profound lactic acidosis resulting from impaired oxidative energy metabolism during exercise.     

Muscle performance and enzymatic adaptations to sprint interval training

Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance. Twelve healthy men (22 +/- 2 yr of age) underwent intense interval training on a cycle ergometer for 7 wk. Training consisted of 30-s maximum sprint efforts (Wingate protocol) interspersed by 2-4 min of recovery, performed three times per week. The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7. Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption (VO2 max) were measured before and after the training program. Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase, total glycogen phosphorylase, phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase. The training program resulted in significant increases in peak power output, total work over 30 s, and VO2 max. Maximal enzyme activity of hexokinase, phosphofructokinase, citrate synthase, succinate dehydrogenase, and malate dehydrogenase was also significantly (P < 0.05) higher after training. It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity, maximum short-term power output, and VO2 max.     

Effect of endurance exercise training on muscle glycogen supercompensation in rats

The purpose of this study was to test the hypothesis that the rate and extent of glycogen supercompensation in skeletal muscle are increased by endurance exercise training. Rats were trained by using a 5-wk-long swimming program in which the duration of swimming was gradually increased to 6 h/day over 3 wk and then maintained at 6 h/day for an additional 2 wk. Glycogen repletion was measured in trained and untrained rats after a glycogen-depleting bout of exercise. The rats were given a rodent chow diet plus 5% sucrose in their drinking water and libitum during the recovery period. There were remarkable differences in both the rates of glycogen accumulation and the glycogen concentrations attained in the two groups. The concentration of glycogen in epitrochlearis muscle averaged 13.1 +/- 0.9 mg/g wet wt in the untrained group and 31.7 +/- 2.7 mg/g in the trained group (P < 0.001) 24 h after the exercise. This difference could not be explained by a training effect on glycogen synthase. The training induced approximately 50% increases in muscle GLUT-4 glucose transporter protein and in hexokinase activity in epitrochlearis muscles. We conclude that endurance exercise training results in increases in both the rate and magnitude of muscle glycogen supercompensation in rats.     

Skeletal muscle deoxygenation during exercise assessed by near-infrared spectroscopy and its relation to expired gas analysis parameters

The present study was performed to determine the relation between oxygenated hemoglobin (oxy-Hb) changes in working muscles and ventilatory parameters. Six active normal subjects, 21 sedentary normal subjects and 16 patients with heart failure performed an incremental exercise with expired gas analysis. Deoxygenation of the vastus lateralis muscle was monitored for oxy-Hb changes using near-infrared spectroscopy. Near the anaerobic threshold (AT), oxy-Hb started to decrease, forming the first inflection point (P1). Near the respiratory compensation point (RCP), the second inflection point (P2) was observed. Oxygen uptake at the AT, RCP, P1 and P2 decreased in magnitude first in the active normal subjects, then in sedentary normal subjects and finally in the heart failure patients. High correlation was demonstrated between AT and P1 (r=0.8, p<0.0005) and between RCP and P2 (r=0.9, p<0.0005). In 12 sedentary normal subjects who underwent repeat exercise, reproducibility was confirmed for both P1 and P2. Constant work rate exercises were performed in 5 sedentary normal subjects, and in all of them the oxy-Hb remained unchanged below the AT work rate, whereas oxy-Hb decreased above the AT work rate. Exercise capacity, with respect to both working muscle deoxygenation and ventilation, could be evaluated in detail by the concomitant use of near-infrared spectroscopy and expired gas analysis.     

Airway anesthesia and respiratory adaptations to dead space loading and exercise

In exercising humans, added external dead space (VD) increases minute ventilation (VI) and causes a slower and deeper breathing pattern (J. Appl. Physiol. 1991; 70:55-62). Recent studies suggest that airway receptors sensitive to topical anesthesia influence VI and breathing pattern responses to exercise and to added VD. We tested these hypotheses with a technique of airway anesthesia (Anesthesia) that has been shown to reliably attenuate airway reflexes. Anesthesia was administered by local laryngopharyngeal application and aerosolized lidocaine inhalation, and was confirmed by citric acid aerosol inhalation challenges. Twelve normal males performed maximal incremental cycle ergometer exercise on 4 d (randomized) after Anesthesia with (Anesthesia VD) and without added VD (Anesthesia Control) and after normal saline inhalation (Saline) with (Saline VD) and without added VD (Saline Control). There were no differences in the VI and breathing pattern responses during exercise between the Saline Control and the Anesthesia Control tests. After both Saline and Anesthesia inhalation, added VD resulted in an increase in VI both at rest and during exercise. At matched VI (98 L/min), the differences in tidal volume (VT) between the Saline Control and Saline VD tests (delta = 0.23 +/- 0.24 L, mean +/- SD) and the Anesthesia Control and Anesthesia VD tests (delta = 0.20 +/- 0.28 L) were not significantly different. Our study had a power of greater than 95% to detect significant differences in VI or breathing pattern due to Anesthesia. We conclude that in normal humans, airway receptors do not play a major role in ventilation and breathing pattern control during exercise, and that the respiratory adaptations to added VD during exercise are not mediated by airway afferent reflexes.     

Cardiovascular adaptations to endurance training and detraining in young and older athletes

A cross-sectional survey was carried out in a sugar estate in central Ethiopia to identify a subgroup for a cohort study on the natural history of HIV infection. HIV prevalence was 2.8% (95% confidence interval [CI], 1.7%-3.9%) in 957 adults aged 15 to 54 years randomly selected for the initial survey. A follow-up survey including only factory workers of the estate aged 18 to 45 years (n = 280) showed a higher HIV prevalence in male factory workers (n = 262) compared with the male estate workers of the same age of the initial survey (n = 484; 8.8% versus 3.1 %; p < .05). Factors independently associated with HIV infection in male factory workers were number of lifetime sexual partners, positive syphilis serology, higher income, and absence of travel outside the residential area. Among male estate workers, only older age was associated with HIV infection. Both factory workers and male estate workers were stable residents and were willing to participate in a long-term study on HIV/ AIDS. However, because of the higher HIV prevalence in factory workers and the higher prevalence of behaviors associated with an increased risk for HIV infection, factory workers were selected for the long-term cohort study on the natural history of HIV infection.     

Autologous calvarial and iliac onlay bone grafts in miniature swine

Calvarial bone has been reported to be superior to iliac bone for onlay bone grafting due to decreased resorption. This study evaluated the physical, histologic, and radiographic characteristics of calvarial and corticocancellous iliac onlay bone grafts in nine Pitman-Moore miniature swine at 2 weeks, and at 1-, 2-, 4-, 6-, 7-, 8-, 10-, and 12-month intervals. Compared with iliac grafts, the calvarial onlay grafts had more than a twofold greater radiographic density. Statistical analysis of the mature grafts using the standard of estimated means of the bone graft volumes revealed 85% retention of the calvarial grafts compared with 34% retention of the grafted iliac bone. There was no subjective difference in the rate or degree of revascularization between the two grafted materials.     

Skeletal muscle buffering capacity and endurance performance after high-intensity interval training by well-trained cyclists

Chronic nicotine administration in animal models evokes a dose-dependent increase in brain nicotinic receptor numbers. Genetically determined variability in nicotinic receptor number in different mouse strains has also been reported, which is thought to affect sensitivity to nicotine, as well as the development of tolerance. Humans self-administer nicotine principally in the form of cigarettes and other tobacco products. The present study compared [3H]nicotine binding in human postmortem brain from thalamus and hippocampus of nonsmoking subjects, subjects who had variable life-long smoking histories and subjects who had quit smoking. A significant increase was seen in [3H]nicotine binding in both hippocampus and thalamus of subjects with life-long smoking histories. In the hippocampus, this change resulted from a change in total receptor number (Bmax), with no change in receptor affinity (Kd). There was also a positive correlation between the degree of smoking, as measured by the average reported packs smoked per day, and the number of nicotine binding sites found in both the hippocampus and thalamus, showing that humans exhibit a dose-dependent increase in brain nicotinic receptor binding. Receptor levels in these brain regions after smoking cessation were at or below those found in the control population, which indicated that smoking-induced changes are reversible after cessation of nicotine treatment. These results suggest that increases in nicotinic receptor levels in the human brain may underlie nicotine tolerance and addiction in smokers.     

Skeletal muscle pathology in systemic sclerosis

OBJECTIVE: Systemic sclerosis (SSc) is characterized by abnormal deposition of collagen in the skin and by visceral involvement. Muscle weakness is a relatively frequent complication of SSc, although severity varies. We studied muscle pathology in patients with SSc with progressive muscle involvement. METHODS: We performed histochemical and immunohistochemical investigations to detect neural cell adhesion molecule (NCAM). RESULTS: Five of the 6 cases of SSc expressed NCAM in atrophic angulated fibers (some fibers stained heavily with oxidative enzymes). CONCLUSION: Neurogenic involvement in SSc is more frequent than reported.     

Skeletal muscle lactate accumulation and creatine phosphate depletion during heavy exercise in congestive heart failure. Cause of limited exercise capacity?

OBJECTIVE: To study the mechanisms of limited exercise capacity and skeletal muscle energy production in male patients with congestive heart failure. DESIGN: Muscle biopsy study. PATIENTS: Skeletal muscle metabolic response to maximal bicycle exercise was studied in 10 patients with chronic congestive heart failure (ejection fraction 0.22 +/- 0.05; peak oxygen consumption, VO2 15.1 +/- 4.9 ml.min-1.kg-1) and in nine healthy subjects (peak VO2 33.5 +/- 6.7 ml.min-1.kg-1). Activities of skeletal muscle enzymes were measured from the vastus lateralis muscle of 48 patients (ejection fraction 0.24 +/- 0.06, peak VO2 17.4 +/- 5.4 ml.min-1.kg-1) and 36 healthy subjects (peak VO2 38.3 +/- 8.4 ml.min-1.kg-1). RESULTS: Although blood lactate levels were lower in patients than in healthy subjects (2.2 +/- 0.3 vs 5.2 +/- 0.6 mmol.l-1; P < 0.001) at peak exercise (96 +/- 11 W for patients and 273 +/- 14 W for controls), skeletal muscle lactate was similarly elevated (25.6 +/- 3.2 vs 22.7 +/- 2.7 mmol.kg-1) and creatine phosphate was equally depressed (P < 0.02) to low levels (7.0 +/- 1.9 vs 6.7 +/- 0.9 mmol.kg-1). The muscle ATP decreased by 21% (P < 0.05) and 8% (P < 0.01) in the patients and controls, respectively. Activities of rate limiting enzymes of the citric acid cycle (alpha-ketoglutarate dehydrogenase) and oxidation of free fatty acids (carnitine palmitoyltransferase II) were 48% and 21% lower than in controls, but the mean phosphofructokinase activity was unchanged in congestive heart failure. CONCLUSIONS: It seems that the main limiting factor of exercise performance during heavy exercise is the same in congestive heart failure and healthy subjects, a high rate of skeletal muscle lactate accumulation and high-energy phosphate depletion. In congestive heart failure, the low activity of aerobic enzymes is likely to impair energy production and lead to lactate acidosis at low workloads.     

Myocardial blood flow distribution in miniature pigs during exercise

Total and regional myocardial blood flow was measured in miniature pigs at rest and during two levels of treadmill exercise, including maximal exercise. Exercise increased the myocardial blood flow in a linear manner with heart rate (r = 0.87). At rest the endocardial/epicardial blood flow ratio was significantly greater than unity with flow favoring the endocardium. Exercise failed to appreciably alter the distribution of coronary blood flow. Thus the myocardium was capable of further dilatation and perfusion of blood without compromising endocardial flow even during the most severe level of exercise when maximal heart rates were attained.     

Early metabolic adaptations of rabbit fast-twitch muscle to chronic low-frequency stimulation

To investigate early adaptive responses to chronic low-frequency stimulation (CLFS), rabbit tibialis anterior (TA) muscles were continuously stimulated at 10 Hz for 8 days, allowed to rest for 1 h, and then subjected to a 15-min fatigue test at 10-Hz stimulation. The contralateral TA muscles which had not been exposed to CLFS, served as controls during the fatigue test. Compared to the controls, the initial tension output of the 8-day prestimulated muscles was reduced by 25%. However, these muscles maintained higher tensions during the fatigue test than the controls. Citrate synthase activity, an indicator of aerobic-oxidative capacity, was only slightly elevated (40%) in the 8-day stimulated muscles. Unlike the controls, the prestimulated muscles failed to produce potentiation during the fatigue test. Control muscles responded to the fatigue test with pronounced reductions in contents of adenosine 5'-triphosphate (ATP), phosphocreatine (PCr), and glycogen, as well as with large increases in contents of inosine monophosphate (IMP), inorganic phosphate (Pi), creatine (Cr), and lactate. Under the same conditions contents of ATP, PCr, Cr, glycogen, lactate, Pi, and IMP were unaltered in the 8-day prestimulated muscles. These findings demonstrated that CLFS for 8 days elicited pronounced alterations in energy metabolism and contractile properties. These adaptive changes occurred prior to fibre type transitions and substantial increases in aerobic-oxidative potential.     

Skeletal muscle ventricles: frontiers in 1995

In different time after application of 12.5 microM colchicine-inhibitor of exoplasmic current to the ischiadicus the quantity of amino acid residues of methionine and cysteine in the sarcoplasmic reticulum decreases, its protein content changes. The Ca(2+)-ATPase activity increases on the 3d day after colchicine application and decreases on the 14th day. Analogical changes are observed in the capacity of the sarcoplasmic reticulum to transport calcium ions, the Michaelis constant in this case being stable. Passive outflow of Ca2+ from the sarcoplasmic reticulum vesicules changes in such a way: the Michaelis constant decreases with a simultaneous increase in the maximal velocity after 14 and 28 days of colchicine application.     

Inverse effect of chronically elevated blood flow on atherogenesis in miniature swine

The effect of chronically elevated blood flow on the development of atherosclerosis in miniature swine was studied. Fistulas connecting the right external iliac artery and vein were surgically created in four swine, while three were not fistulated. Pulsed Doppler velocity detection cuffs placed around the abdominal aorta and both iliac arteries of all pigs permitted chronic measurements of blood velocity, blood velocity distributions, and blood flow. All swine were fed an atherogenic diet consisting of 20% beef tallow, 3% cholesterol, and 5% cholic acid for 6 months. This diet elevated the serum cholesterol to values exceeding 500 mg/100 ml. Creation of the arteriovenous fistula (AVF) markedly elevated blood velocity and flow in the abdominal aorta and in the shunted iliac artery. In the shunted animals the aortic blood flow was 42.1 +/- 2.0 ml/sec compared with 17.3 +/- 1.4 ml/sec in the unshunted swine. The velocity distribution pattern across the vessel was also indicative of an elevated wall shear stress. After 6 months, the animals were killed and the arterial vessels examined macroscopically and microscopically for the presence of atherosclerotic lesions. In the shunted pigs, 17 +/- 15% of the lumenal surface was occupied by sudanophilic lesions, whereas 80 +/- 8% of the surface was covered by lesions in the unshunted (control) pigs. From these studies, it is apparent that mechanical factors related to blood flow rates can influence the development of atherosclerotic lesions in swine.