Muscle In Chronic Heart Failure Research Articles

Altered expression of myosin heavy chain in human skeletal muscle in chronic heart failure.

To explore further alterations in skeletal muscle in chronic heart failure (CHF), we examined myosin heavy chain (MHC) isoforms from biopsies of the vastus lateralis in nine male patients with class II-III (CHF) (left ventricular ejection fraction (LVEF) 26 +/- 11%, peak oxygen consumption (peak VO2) 12.6 +/- 2 mL.kg-1.min-1) and nine age-matched sedentary normal males (NL). The relative content of MHC isoforms I, IIa, and IIx was determined by gel electrophoresis as follows: The normal sedentary group (NL) had a higher percent of MHC type I when compared with the patients (NL 48.4 +/- 7% vs CHF patients 24 +/- 21.6%, P < 0.05, no difference between MCH IIa (NL 45.1 +/- 10.5% vs CHF 56.0 +/- 12.5%), and CHF patients had a higher relative content of MHC type IIx than did the normal group (NL 6.5 +/- 9.6% vs CHF 20.0 +/- 12.9%, P < 0.05. Three of nine patients had no detectable MHC type I. In patients relative expression of MHC type I (%) was related to peak VO2 (r = 0.70, P < 0.05). Our results indicate that major alterations in MHC isoform expression are present in skeletal muscle in CHF. These alterations parallel previously reported changes in fiber typing that may affect contractile function i skeletal muscle and possibly exercise performance. The absence of MHC type I in some CHF patients suggests that skeletal muscle changes in this disorder are not solely a result of deconditioning, buy may reflect a specific skeletal muscle myopathy in this disorder.

Biochemical analysis of muscle biopsy in overnight fasting patients with severe chronic heart failure.

To better characterize the role of skeletal muscle in chronic heart failure we studied energetic charge, metabolites and enzyme activity in the energy production pathway. We selected 15 males with severe chronic heart failure (NYHA class III, stable clinical conditions and in normal nutritional status) and seven controls. Controls and patients were submitted to biopsy of the vastus lateralis muscle in resting and fasting conditions. Hormone profiles were also evaluated. Our results showed near normal ATP, ADP and AMP concentrations, but there were substantially more reductions in glycogen (46 +/- 5 vs 77 +/- 6 mumoles glycosidic units.g-1 fresh tissue) and creatine phosphate (5 +/- 1 vs 13 +/- 1 mumoles.g-1 fresh tissue) in patients than in controls. We also found a reduction in glycolytic activity (pyruvate kinase 1009 +/- 79 vs 1625 +/- 26 nmoles. min-1.mg protein-1), despite normal tricarboxylic acid cycle velocity, an increase in alanine amino-transferase (964 +/- 79 vs 425 +/- 34 nmoles. min-1.mg protein-1) and in aspartate aminotransferase (515 +/- 44 vs 291 +/- 56 nmoles.min-1.mg protein-1). An increase was also observed in total NADH cytochrome c reductase (128 +/- 14 vs 68 +/- 5 nmoles.min-1.mg protein-1), while cytochrome oxidase activity was normal. The cortisol/insulin ratio was slightly elevated (77 +/- 4 vs 32 +/- 12). In conclusion, normonutritive patients with severe heart failure show an imbalance in the energy production/utilization ratio. The impairment is probably due both to a decrease in production and an increase in consumption of energy owing to greater cellular workload and/or a hypercatabolic state.

Peripheral and respiratory muscles in chronic heart failure.

It is well-established that in patients with congestive heart failure (CHF), exercise is limited by fatigue and shortness of breath. The poor correlation between the fatigue and indices of central haemodynamic function might indicate that peripheral muscle alterations contribute to impaired exercise capacity. Intrinsic abnormalities of the skeletal muscles have been suggested as a possible explanation. Since the shortness of breath correlates poorly with changes in lung function, changes in the respiratory muscles have been investigated. Studies have demonstrated diaphragmatic myopathy and atrophy similar, in part, to the changes in peripheral skeletal muscles. In CHF, type I (slow twitch) fibre atrophy is seen in respiratory as well as in peripheral muscles. The mechanism of these alterations remains to be elucidated. Studies into the mechanism of muscle dysfunction in congestive heart failure are relevant to the prospect of treatment of the changes in peripheral and respiratory muscles.

Endothelial control of lower limb blood flow in chronic heart failure.

Limitation of the blood supply to skeletal muscle in chronic heart failure may contribute to the symptoms of fatigue and diminished exercise capacity. The pathophysiology underlying this abnormality is not known. The purpose of this study was to assess the effect of endothelium dependent and independent vasodilator agents on blood flow in the leg of patients with heart failure. Blood flow in the leg was measured in patients with heart failure (n = 20) and compared with that in patients with ischaemic heart disease and normal left ventricular function (n = 16) and patients with chest pain and normal coronary arteries (n = 8). External iliac artery blood flow was measured using intravascular Doppler ultrasound and quantitative angiography. Flow was recorded at rest and in response to bolus doses of the endothelium independent vasodilator, papaverine. Endothelium dependent responses were measured by infusion of acetylcholine and substance P. Mean (SEM) baseline blood flow was reduced at rest (2.9 (0.4) v 4.5 (0.3) ml/s, P < 0.001) and vascular resistance was raised (37.4 (3.6) v 27.1 (3.0) units, P < 0.05) in patients with heart failure compared with that in controls. The peak blood flow response to papaverine (8 mg), acetylcholine (10(-7)-10(-5) mol/l), and substance P (5 pmol/min) was reduced in heart failure, with greater impairment of the response to acetylcholine than substance P. There was a correlation between baseline blood flow in the heart failure group and diuretic dose (r = -0.62, P = 0.003), New York Heart Association classification (r = -0.65, P = 0.002), and left ventricular ejection fraction (r = 0.80, P = 0.0004). There is reduced blood flow and raised vascular resistance at rest in the legs of patients with heart failure. The degree of impaired blood flow in the leg correlates with the severity of heart failure. There is impairment of the response to both endothelium dependent and independent vasodilators. Abnormal function of the vascular myocyte in heart failure may explain these results as would structural abnormalities of the resistance vessels.

Physical training improves skeletal muscle metabolism in patients with chronic heart failure

Objectives. This study investigated the effects of physical training on skeletal muscle metabolism in patients with chronic heart failure.Background. Skeletal muscle metabolic abnormalities in patients with chronic heart failure have been associated with exercise intolerance. Muscle deconditioning is a possible mechanism for the intrinsic skeletal muscle metabolic changes seen in chronic heart failure.Methods. We used phosphorus-31 nuclear magnetic resonance spectroscopy to study muscle metabolism during exercise in 12 patients with stable ischemic chronic heart failure undergoing 8 weeks of home-based bicycle exercise training in a randomized crossover controlled trial. Changes in muscle pH and concentrations of phosphocreatine and adenosine diphosphate (ADP) were measured in phosphorus-31 spectra of calf muscle obtained at rest, throughout incremental work load plantar flexion until exhaustion and during recovery from exercise. Results were compared with those in 15 age-matched control subjects who performed a single study only.Results. Before training, phosphocreatine depletion, muscle acidification and the increase in ADP during the 1st 4 min of plantar flexion exercise were all increased (p < 0.04) compared with values in control subjects. Training produced an increase (p < 0.002) in incremental plantar flexion exercise tolerance. After training, phosphocreatine depletion and the increase in ADP during exercise were reduced significantly (p < 0.003) at all matched submaximal work loads and at peak exercise, although there was no significant change in the response of muscle pH to exercise. After training, changes in ADP were not significantly different from those in control subjects, although phosphocreatine depletion was still greater (p < 0.05) in trained patients than in control subjects. The phosphocreatine recovery half-time was significantly (p < 0.05) shorter after training, althrough there was no significant change in the half-time of adenosine diphosphate recovery. In untrained subjects, the initial rate of phosphocreatine resynthesis after exercise (a measure of the rate of oxidative adenosine triphosphate [ATP]synthesis) and the inferred maximal rate of mitochondrial ATP synthesis were reduced compared with rates in control subjects (p < 0.003) and both were significantly increased (p < 0.05) by training, so that they were not significantly different from values in control subjects.Conclusions. The reduction in phosphocreatine depletion and in the increase in ADP during exercise, and the enhanced rate of phosphocreatine resynthesis in recovery (which is independent of muscle mass) indicate that a substantial correction of the impaired oxidative capacity of skeletal muscle in chronic heart failure can be achieved by exercise training.

Alterations of skeletal muscle in chronic heart failure.

The present study was designed to define the prevalence and characteristics of skeletal muscle alterations in patients with chronic heart failure (CHF) and their relation to exercise capacity. The ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry in 57 patients with CHF and 18 healthy controls. The volume density of mitochondria (Vvm) and the surface density (Svmc) of mitochondrial cristae were evaluated as a structural correlate of oxidative capacity of skeletal muscle. Vvm and Svmc were reduced by approximately 20% in patients with severe CHF irrespective of age and etiology. The cytochrome oxidase activity in mitochondria as determined by cytochemistry and subsequent morphometry in a subset of patients (n = 10) was significantly decreased in heart failure (p less than 0.01). The capillary length density of skeletal muscle was reduced in CHF (n = 12, p less than 0.05), and the fiber type distribution was shifted to type II fibers (n = 15, p less than 0.05). Vvm and Svmc were significantly related to peak exercise VO2 (r = 0.56, p less than 0.001, n = 60) and to VO2 at anaerobic threshold (r = 0.535, p less than 0.0001, n = 60). In 16 patients with severe heart failure, Vvm was inversely related to the duration of heart failure (r = 0.545, p less than 0.03). In 11 patients who underwent repeat biopsies after 4 months, a correlation was observed between the change in Vvm and the change in peak exercise VO2 (r = 0.89, p less than 0.001). These findings indicate that patients with CHF develop significant ultrastructural abnormalities of skeletal muscle reflecting a depressed oxidative capacity of working muscle. It appears that these alterations of skeletal muscle contribute to the decreased exercise capacity of these patients but are, in principle, reversible by an effective treatment regimen.