The effect of physical training on skeletal muscle in patients with chronic heart failure.

BACKGROUND: The improvement of exercise capacity in patients with chronic heart failure (CHF) by physical training has been connected with reversal of the abnormalities in muscle fiber distribution and with the reduced activity of the enzymes of oxidative metabolism in skeletal muscle. However, the change in fiber type distribution induced by training is controversial and in previous studies the activities of the rate-limiting enzymes of the metabolic pathways have not been measured. AIMS: To examine the effect of dynamic training on percentage distribution of muscle fibers, on activities of the rate-limiting enzymes of the metabolic pathways and on electrophysiology in skeletal muscle. METHODS: A total of 27 patients with stable CHF (NYHA class II-III) were randomized to a training (N=12) or a control (N=15) group. The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months using a load corresponding to 50-60% of their peak oxygen consumption. This was followed by a 3-month training period at home according to personal instructions. The control group did not change its physical activities. We studied muscle histology and measured the activities of the rate-limiting enzymes of anaerobic glycolysis (phosphofructokinase, PFK), glycogenolysis (phosphorylase), citric acid cycle (alpha-ketoglurate dehydrogenase, KGDH) and fatty acid oxidation (carnitinepalmitoyl transferase I and II, CPT I and II) from biopsies of the vastus lateralis muscle at baseline and after 3 and 6 months. Muscle strength and strength endurance with surface EMG and macro EMG of the right knee extensors were also determined. RESULTS: Exercise capacity, particularly submaximal, improved in the training group. The activity of PFK rose significantly but that of the other enzymes did not when compared with the change in the controls. Training had no effect on the percentage distribution of slow-twitch and fast-twitch muscle fibers or on capillary density around these fibers in skeletal muscle. Maximum voluntary force, strength endurance and the function of motor units remained unaffected. CONCLUSIONS: Dynamic training results in improved exercise endurance in CHF. In skeletal muscle, the capacity of anaerobic glycolysis is increased but that of the citric acid cycle and fatty acid oxidation is not. Furthermore, the improvement in exercise endurance seems to be independent of changes in the percentage distribution of muscle fibers, capillarity or electrophysiological factors.

The effect of physical training on hormonal status and exertional hormonal response in patients with chronic congestive heart failure.

BACKGROUND: Physical training improves exercise capacity in patients with chronic heart failure. It decreases plasma noradrenaline at rest, which may be prognostically favourable. The effect on atrial natriuretic peptide, another prognostic factor, and on catabolic and anabolic hormones remains unknown. Furthermore, to our knowledge, the contribution of exertional hormonal responses to the improved exercise capacity has not been evaluated. METHODS: 27 patients with stable chronic heart failure (New York Heart Association class II-III) were randomized to training (n=12) and control (n=15) groups. The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months. The load corresponded to 50-60% of their peak oxygen consumption. For the next 3 months they exercised at home according to personal instructions. The control group did not change its physical activities. The levels of hormones regulating the cardiovascular system and metabolism were determined at rest and after graded maximal exercise and during exercise with constant submaximal workload. RESULTS: Submaximal exercise capacity increased significantly and peak oxygen consumption tended to improve by 12% in the training group. The plasma noradrenaline at rest tended to decrease by 19%. The plasma level of N-terminal pro atrial natriuretic peptide did not change. Serum cortisol, a catabolic hormone, was normal at baseline and remained unchanged. The serum levels of anabolic hormones, growth hormone and insulin, as well as dehydroepiandrosteronesulfate and free testosterone were within a normal range at baseline. They were not altered by training. The dehydroepiandrosteronesulfate/cortisol, and the free testosterone/cortisol ratios, reflecting anabolic/catabolic balance, did not change, either. Training resulted in a higher peak noradrenaline response during graded maximal exercise. The rise in serum cortisol during exercise tended to attenuate. CONCLUSION: Physical training, which improves exercise capacity, does not have an unfavourable effect on anabolic/catabolic balance or neurohumoral activation in patients with congestive heart failure. It decreases plasma noradrenaline at rest. Minor changes in hormonal responses during exercise emerged after physical training which unlikely contribute to the improved exercise capacity.

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.

Effect of physical training on exercise capacity and gas exchange in patients with chronic heart failure.

Decreased exercise capacity is the main factor restricting the daily life of patients with chronic congestive heart failure (CHF). We performed a controlled, randomized study to evaluate the effect of dynamic exercise training of moderate intensity on exercise capacity and gas exchange in patients with CHF. Twenty-seven patients with stable CHF, New York Heart Association (NYHA) functional class II and III, were randomized to training (n = 12) and control (n = 15) groups. During a 3-month period, the training group underwent a supervised physical training program using a bicycle ergometer for 30 min 3 times a week at a load corresponding to 50 to 60% of their peak oxygen consumption. Thereafter, they were advised to continue training at home for the next 3 months. The control group did not change their previous physical activity. A graded maximal exercise test with respiratory gas analysis and an endurance test with constant submaximal workload were performed at baseline and after 3 and 6 months. The exercise endurance increased from 14.7 +/- 2.0 to 27.8 +/- 2.7 min (p < 0.01) and the peak oxygen consumption tended to improve from 19.3 +/- 1.6 to 21.7 +/- 2.3 mL/kg/min (p = 0.09) during the supervised training period. At submaximal workloads, minute ventilation was reduced by 16% per se (p < 0.01) and by 7% in proportion to carbon dioxide production (p < 0.05). Oxygen consumption at the anaerobic threshold increased from 10.5 +/- 0.8 to 12.7 +/- 1.0 mL/kg/min (p < 0.05). The positive training effects were associated with an improvement in the NYHA functional class. The effects of supervised training were preserved during the home-based training period. The results indicate that physical training of moderate intensity significantly improves the exercise capacity and reduces the exaggerated ventilatory response to exercise, particularly at submaximal working levels in patients with CHF. This is associated with alleviation of symptoms.

Reversal of autonomic derangements by physical training in chronic heart failure assessed by heart rate variability.

Decreased heart rate variability has been associated with chronic congestive heart failure (CHF). We evaluated the effect of physical training on heart rate variability in 20 patients with CHF (NYHA class II-III) randomized to training (n = 8) and control (n = 12) groups. The training group underwent 3 months of physical training, by exercising on a bicycle ergometer for 30 min three times a week at a load corresponding to 50-60% of their peak oxygen consumption. Heart rate variability was assessed from 20-h ambulatory ECG recordings in the frequency domain, determined by high (0.15-0.40 Hz), low (0.04-0.15 Hz) and very low frequency (0.008-0.04 Hz) components. The high frequency component increased by 22-55% in the training group during the day (P = 0.0001) but not at night. The increase was seen during both sedentary and active periods. The low frequency/high frequency ratio attenuated in the training group during the day (P = 0.05) whereas an increase was seen in the control group throughout the day (P = 0.0003). Training lengthened the exercise duration by 71% at a submaximal workload (P = 0.01) and tended to increase the peak oxygen consumption by 15% (P = 0.09). These remained unchanged in the control group. In conclusion, physical training, which improves exercise capacity, ameliorates the autonomic derangement in CHF by increasing the parasympathetically mediated component of heart rate variability. It may thus influence favourably the prognosis of the disease.

Calcitonin gene-related peptide is not elevated in rat plasma by heart failure or by neutral endopeptidase inhibition.

Some studies have indicated that plasma calcitonin gene-related peptide (CGRP) increases in congestive heart failure (CHF). In vitro, neutral endopeptidase (NEP) cleaves CGRP. We studied CGRP-like immunoreactivity (CGRP-ir) in rat plasma in a coronary artery-ligation model of CHF with and without NEP inhibition. Rats with CHF (n = 6) and sham-operated controls (n = 6) were administered vehicle and, separately, SCH 34826, a NEP inhibitor, subcutaneously 90 mg/kg. Plasma sample was taken 60 minutes later. Seventeen untreated coronary-ligated rats with various degrees of CHF were studied separately. Systolic arterial pressure (SAP) was measured while conscious. All rats were killed by exsanguination, and heart and lungs were removed and weighed. In CHF rats, plasma atrial natriuretic peptide after vehicle (basal ANP) was 7.6-fold, but basal CGRP-ir was similar compared to controls. After SCH 34826, plasma CGRP-ir decreased marginally in CHF rats (57-> 51 ng/l, p = 0.011), and ANP increased 1.8-fold (418-> 730 ng/l, p = 0.001). In controls, these changes by SCH 34826 were small. Basal ANP correlated strongly with relative weight of heart (HE; R = 0.93, p < 0.001) and lungs (LU; R = 0.96, p < 0.001). There was no correlation between basal CGRP-ir, basal plasma renin activity (PRA), HE and LU. In the untreated coronary-ligated rats, plasma CGRP-ir did not correlate with HE, LU, SAP, plasma ANP or PRA, but plasma ANP correlated with HE (R = 0.62, p = 0.011) and LU (R = 0.70, p = 0.002). We conclude that, in rat plasma, CGRP-ir is not elevated either by NEP inhibition, or in post-infarction CHF.

Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters.

Using a double-blind, crossover protocol, we studied the possible effects of a 4-day combined L-arginine, L-ornithine, and L-lysine supplementation (each 2 g/day, divided into two daily doses) on 24-hr level of serum human growth hormone (hGH) and insulin in 11 competitive weightlifters, ages 19 to 35 yrs. Three similar daily hGH peaks, seemingly preceded by a decrease in serum insulin concentration, were found during both amino acid and placebo supplementation. Supplementation did not affect the physiological variation of serum hGH concentration (treatment and treatment x time interaction: p = 0.43-0.55). Analogously, serum insulin levels were not higher after amino acid supplementation. Therefore the ergogenic value of low-dose oral amino acid supplementation in increasing hGH or insulin secretion seems questionable.