ATP, phosphocreatine and lactate in exercising muscle in mitochondrial disease and McArdle's disease.

We studied exercise-induced changes in the adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate levels in the skeletal muscle of mitochondrial patients and patients with McArdle's disease. Needle muscle biopsy specimens for biochemical measurement were obtained before and immediately after maximal short-term bicycle exercise test from 12 patients suffering from autosomal dominant and recessive forms of progressive external ophthalmoplegia and multiple deletions of mitochondrial DNA (adPEO, arPEO, respectively), five patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3243 A-->G point mutation, and four patients with McArdle's disease. Muscle ATP and PCr levels at rest or after exercise did not differ significantly from those of the controls in any patient group. In patients with mitochondrial disease, muscle lactate tended to be lower at rest and increase more during exercise than in controls, the most remarkable rise being measured in patients with adPEO with generalized muscle symptoms and in patients with MELAS point mutation. In McArdle patients, the muscle lactate level decreased during exercise. No correlation was found between the muscle ATP and PCr levels and the respiratory chain enzyme activity.

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.

Effect of ethanol drinking, hangover, and exercise on adrenergic activity and heart rate variability in patients with a history of alcohol-induced atrial fibrillation.

To elucidate the mechanism of alcohol-induced atrial fibrillation (AF) we studied the heart rate variability and parameters of the adrenergic system during alcohol intake, hangover, and exercise in 6 men (mean age 43 years) prone to alcohol-induced AF, together with 6 age-matched controls. The ambulatory (15 hour) electrocardiogram was recorded and blood samples were taken for lymphocytic beta adrenoceptor, plasma catecholamine, and cyclic adenosine monophosphate (cAMP) measurements before and after alcohol intake (blood alcohol 1.5 per thousand), during hangover, and after a standardized bicycle exercise test. The beta-adrenoceptor density in lymphocytes was unchanged in the control group after alcohol intake or during hangover. Each of the AF patients had an increase in beta-adrenoceptor density after ethanol drinking (mean increase 29%, p <0.05). The hangover or exercise beta-receptor values did not differ from those in corresponding controls. Plasma adrenaline concentration tended to decrease and noradrenaline to increase after drinking and during hangover in both groups. Plasma cAMP levels were lower in patients after drinking than in controls (p <0.05). The exercise values of the adrenergic parameters were very similar in AF patients whether or not preceded by alcohol. Analysis of ambulatory electrocardiography showed a very low rate of ectopic beats in both AF patients and controls. Analysis of heart rate variability revealed a tendency toward an increase in sympathetic/parasympathetic component ratio (low-frequency/high-frequency ratio) in AF patients, but not in controls, after ethanol drinking. In conclusion, no signs of arrhythmogenic cardiac disease were detected in patients with AF to explain the tendency toward AF. Increases in beta-adrenoceptor density and low-frequency/high-frequency ratio during ethanol intoxication in patients with AF suggest an exaggerated sympathetic reaction.

Haemodynamic, neuroendocrine and metabolic correlates of circulating cytokine concentrations in congestive heart failure.

OBJECTIVES: Increased activity of pro-inflammatory cytokines in the circulation has been observed in many, though not all, patients with congestive heart failure. To identify the predictors of cytokine activation in congestive heart failure, we assessed the relationship of peripheral and hepatic venous cytokines to central haemodynamics, neuroendocrine status and intermediary metabolism in patients with moderate or severe congestive heart failure. PATIENTS AND METHODS: Concentrations of tumour necrosis factor-alpha, soluble tumour necrosis factor-receptor II and interleukin 6 were measured from peripheral and hepatic venous plasma in 58 adult cardiac patients, of whom 44 had congestive heart failure, undergoing heart catheterization, echocardiography and assessment of selected neuroendocrine and metabolic characteristics. RESULTS: Peripheral venous soluble tumour necrosis factor-receptor II was directly related to NYHA class (rs = 0.46, P < 0.001) and inversely to 6-min walking distance (rs = -0.46, P < 0.001). Peripheral venous tumour necrosis factor-alpha was related to 6-min walking distance (rs = -0.37, P < 0.01), but like soluble tumour necrosis factor-receptor II, was unrelated to other haemodynamic and neuroendocrine measurements. Peripheral venous interleukin 6 correlated with NYHA class (rs = 0.66, P < 0.001) and 6-min walking distance (rs = -0.52, P < 0.001). In addition, interleukin 6 was related to right atrial pressure (rs = 0.55, P < 0.001), pulmonary artery wedge pressure (rs = 0.50, P < 0.001) and left ventricular ejection fraction (rs = -0.39, P < 0.01); in multivariate analysis, only right atrial pressure was an independent predictor of interleukin 6 concentration (P < 0.001). Comparisons between patients with and without congestive heart failure showed significantly higher hepatic venous tumour necrosis factor-alpha, soluble tumour necrosis factor-receptor II and interleukin 6 in the heart failure group; the differences in peripheral venous cytokines were less consistent. CONCLUSIONS: In cardiac patients, increased plasma tumour necrosis factor-alpha and soluble tumour necrosis factor-receptor II are associated with symptoms of heart failure and poor exercise capacity, while the most important predictor of increased interleukin 6 is elevated systemic venous pressure. Different but still unknown mechanisms may be responsible for the increased release of cytokines in congestive heart failure.

Heart failure ketosis.

OBJECTIVE: To assess whether blood ketone bodies are increased in congestive heart failure (CHF). METHODS: Thirteen patients with CHF and 11 cardiac patients without CHF took part in the study. Blood acetoacetate and b-hydroxybutyrate levels and the pertinent metabolic and hormonal milieu were measured during 20 h fast and after 2 h glucose infusion. RESULTS: The averaged blood ketone body and free fatty acid levels were significantly higher during the fast and also remained higher after glucose infusion in patients with CHF than in the control group. The areas under ketone body concentration time curve over the last 8 h of the fast were 3522 +/- 662 mumol L-1 h-1 (SE) and 1789 +/- 192 mumol L-1 h-1 in patients with and without CHF, respectively (P = 0.022). Circulating noradrenaline and growth hormone were higher but glucagon lower in patients with CHF than in the controls (P < 0.05 for all differences) whereas the glucose and insulin concentrations were comparable in the study groups. At the time of peak ketonaemia the glucagon-to-insulin ratio was lower in patients with CHF than in patients without CHF (P = 0.04). CONCLUSIONS: These data suggest that severe CHF is a ketosis-prone state. Augmented supply of free fatty acids for ketogenesis due to increased stress hormone-related lipolysis is one likely mechanism.

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.

Blood ketone bodies in congestive heart failure.

OBJECTIVES: The present study was designed to assess whether blood ketone bodies are elevated in congestive heart failure (CHF) and whether ketonemia is related to the hemodynamic and neurohumoral abnormalities of CHF. BACKGROUND: In CHF, consumption of the body's fat stores may become abnormally high, contributing to the development of cardiac cachexia. Increased mobilization of free fatty acids could, in theory, augment ketogenesis, but whether patients with CHF are prone to ketosis remains unknown. METHODS: Forty-five patients with chronic CHF (mean age [+/- SD] 57 +/- 13 years) and 14 control subjects free of CHF (mean age 53 +/- 13 years) underwent invasive and noninvasive cardiac studies and determination of blood ketone bodies (acetoacetate plus beta-hydroxybutyrate), circulating free fatty acids, glucose, lactate, insulin, glucagon, growth hormone, cortisol, norepinephrine, N-terminal proatrial natriuretic peptide, tumor necrosis factor-alpha and interleukin-6 after an overnight fast. RESULTS: Patients with CHF had elevated blood ketone bodies (median 267 mumol/liter, range 44 to 952) compared with control subjects (median 150 mumol/liter, range 31 to 299, p < 0.05). In the total study group, blood ketone bodies were related to pulmonary artery wedge pressure (r5 = 0.45, p < 0.001), left ventricular ejection fraction (r3 = -0.37, p < 0.01), right atrial pressure (r3 = 0.36, p < 0.01) and circulating concentrations of free fatty acids (r5 = 0.52, p < 0.001), glucose (r5 = -0.39, p < 0.001), norepinephrine (r3 = 0.45, p < 0.001), growth hormone (r5 = 0.30, p < 0.05) and interleukin-6 (r3 = 0.27, p < 0.05). In multivariate analysis, left ventricular ejection fraction, serum free fatty acids and serum glucose were independent predictors of ketonemia. CONCLUSIONS: Blood ketone bodies are elevated in CHF in proportion to the severity of cardiac dysfunction and neurohormonal activation. This may be at least partly attributable to increased free fatty acid mobilization in response to augmented neurohormonal stimulation. Additional studies are needed to identify the detailed mechanisms and clinical implications of CHF ketosis.

Effect of beta-blocking agents with and without intrinsic sympathomimetic activity on work efficiency in healthy men.

In order to evaluate the effect of beta-blocking agents with and without intrinsic sympathomimetic activity (ISA) on work efficiency in healthy subjects, we studied the haemodynamic and gas exchange parameters, as well as blood lactate concentrations, during a graded maximal bicycle exercise test performed after perorally given propranolol (PRO) and pindolol (PIN) in seven healthy men. The medications (PRO: 80 mg x 2/day, PIN: 10 mg x 2/day, for seven days) were given in a placebo (PLA) controlled, double-blind, randomized, cross-over fashion. Both the drugs reduced heart rate and blood pressure during exercise equally compared with the placebo. The oxygen uptake at submaximal work loads, as well as at the maximum, was constantly and equally reduced by PRO and PIN compared with PLA. The anaerobic threshold was reached at a slightly lower oxygen uptake for both the drugs compared with the placebo (P < 0.05). No significant difference was, however, observed in the work levels at which the ventilatory anaerobic threshold was reached. Moreover, the gross efficiency, i.e. the amount of work performed at a certain energy consumption level (aerobic + anaerobic), was increased by both PRO (26.7 +/- 0.5%, P < 0.02 vs PLA: 24.7 +/- 0.5%) and PIN (26.5 +/- 0.5%, P < 0.05 vs PLA) at a submaximal work load of 240 W. The results indicate that beta-blocking agents propranolol and pindolol slightly and equally reduce maximal work performance, but increase the efficiency of submaximal work in a way that a certain amount of external work can be done with smaller consumption of oxygen. These findings may contribute to the benefit of beta-blocking agents in patients with coronary heart disease.

Skeletal muscle fiber distribution influences serum high-density lipoprotein cholesterol level.

Earlier we have shown a significant positive association between muscle fiber distribution, i.e. percentage of slow-twitch (ST) fibers in the vastus lateralis muscle, and serum high-density lipoprotein cholesterol (HDL-C) level. This association may be due to the fact that ST fibers have a high capacity for oxidative energy metabolism and a high number of surrounding capillaries. These fibers have a high capacity to metabolize fatty acids liberated by lipoprotein lipase (LPL) from triglyceride-rich lipoproteins. This in turn elevates serum HDL-C levels. Thus, a high percentage of ST fibers (ST-%) may be one factor having a beneficial effect on serum HDL-C concentration. A high ST-% may also increase the likelihood that a person will become involved in an endurance type of physical activity, which further increases serum HDL-C concentration by increasing further LPL activity in the capillary bed of skeletal muscle. In this paper we present a hypothetical background of the role that ST fibers may have on serum lipid and lipoprotein profile.

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.

Alteration of regulatory enzyme activities in fast-twitch and slow-twitch muscles and muscle fibres in low-intensity endurance-trained rats.

The effect of progressive, low-intensity endurance training on regulatory enzyme activities in slow-twitch (ST) and fast-twitch (FT) muscle fibres was studied in 32 rats. Of those rats 16 were trained on a treadmill at a running speed of 10 m.min-1 5 days a week over an 8-week period. Running time was progressively increased from 15 min to 2 h.day-1. Of the rats 4 trained and 4 sedentary rats were also subjected to acute exhausting exercise. Enzyme activities of phosphofructokinase 1 (PFK1) from glycolysis, alpha-ketoglutarate dehydrogenase (alpha-KGDH) from the Krebs cycle and carnitine palmitoyltransferase (CPT I and II) from fatty acid metabolism in soleus, tibialis anterior and gastrocnemius muscles were measured in trained and sedentary rats. Enzyme activities of individual ST and FT fibres were measured from the freeze-dried gastrocnemius muscle of 8 trained and 8 sedentary rats. In the sedentary rats the activity of PFK1 in tibialis anterior and soleus muscles was 141% and 41% of the activity in gastrocnemius muscle, respectively. The activity of alpha-KGDH in tibialis anterior and soleus muscles was 164% and 278% of the activity in gastrocnemius muscle, respectively. The activity of CPT I in tibialis anterior and gastrocnemius muscles were at the same level, but in soleus muscle the activity was 127% of that in mixed muscle. Endurance training increased enzyme activities of alpha-KGDH and CPT I significantly (P < 0.05) in gastrocnemius muscle but not in soleus or tibialis anterior muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Ineffective ventilation during exercise in patients with chronic congestive heart failure.

The pathophysiologic mechanisms causing exertional breathlessness in patients with chronic congestive heart failure (CHF) are not fully understood. Therefore, we have studied whether the ventilation in such patients is ineffective during exercise. Thirteen patients with treated chronic CHF (New York Heart Association class II-IV) and eight healthy controls underwent a maximal bicycle ergometer test with continuous analysis of expired air and frequent arterial blood sampling for gas and lactate analysis. All subjects were non-smokers and none had any signs of a pulmonary disease. Peak O2 consumption of the patients was 14.9 +/- 5.3 ml min-1 kg-1 and that of controls 33.6 +/- 7.5 ml min-1 kg-1. In patients with CHF the ratio of pulmonary dead space to tidal volume was significantly elevated at peak exercise compared with that of the controls (0.36 +/- 0.08 vs. 0.20 +/- 0.07, P less than 0.05). The ventilatory equivalent for CO2 (VE:VCO2) was also significantly higher in patients than in controls during exercise (P less than 0.05). Furthermore, both the ventilatory equivalents for CO2 and O2 (VE:VO2) had a significant inverse correlation with peak O2 consumption (P less than 0.001 for VE:VCO2 and P less than 0.05 for VE:VO2), O2 consumption at anaerobic threshold (P less than 0.01) and O2-pulse (P less than 0.001) among the patients. During exercise the arterial PO2 and PCO2 remained normal in patients and controls. These data indicate that in patients with chronic CHF wasted ventilation is pathologically increased during exercise, and this is related to the severity of the disease. Chronic CHF is not associated with decreased ventilatory reserve, hypoxaemia or alveolar hyperventilation. The ineffectiveness of ventilation is probably an important cause of exertional breathlessness in patients with CHF.