Akiko Hanada

Skeletal Muscle Metabolism Limits Exercise Capacity in Patients With Chronic Heart Failure

BACKGROUND Several studies have indicated that skeletal muscle is important in determining the exercise capacity of patients with chronic heart failure (CHF). However, this theory has been investigated only in experiments based on local exercise involving a small muscle mass. We investigated skeletal muscle metabolism during maximal systemic exercise to determine whether muscle metabolism limits exercise capacity in patients with CHF. We also studied the relationship between muscle metabolic abnormalities during local and systemic exercise. METHODS AND RESULTS Skeletal muscle metabolism was measured during maximal systemic exercise on a bicycle ergometer by a combination of the metabolic freeze method and 31P magnetic resonance spectroscopy in 12 patients with CHF and 7 age- and size-matched normal subjects. We also evaluated skeletal muscle metabolism during local exercise while subjects performed unilateral plantar flexion. Muscle phosphocreatine (PCr) was nearly depleted during maximal systemic exercise in patients with CHF and normal subjects (12.5+/-0.04% and 12.3+/-0.07%, respectively, of initial level). PCr depletion occurred at a significantly lower peak oxygen uptake (peak VO2) in patients with CHF than in normal subjects (CHF, 20.2+/-3.0 versus normal, 31.8+/-3.7 mL . min-1 . kg-1, P<0. 0001). Muscle metabolic capacity, evaluated as the slope of PCr decrease in relation to increasing workload, was correlated with peak VO2 during maximal systemic exercise in patients with CHF (r=0.83, P<0.001). Muscle metabolic capacity during local exercise was impaired in patients with CHF and was correlated with capacity during systemic exercise (r=0.76, P<0.01) and with peak VO2 (r=0. 83, P<0.001). CONCLUSIONS These results suggest that impaired muscle metabolism associated with early metabolic limitation determines exercise capacity during maximal systemic exercise in patients with CHF. There was a significant correlation between muscle metabolic capacity during systemic and local exercise in patients with CHF.

Metabolic abnormality of calf skeletal muscle is improved by localised muscle training without changes in blood flow in chronic heart failure

Objective To investigate whether localised skeletal muscle training, which does not have a great influence on the heart, improves abnormalities of calf muscle metabolism in patients with chronic heart failure. Methods Seven cardiac patients in New York Heart Association class II and III undertook a random order crossover trial. Training consisted of unilateral calf plantar flexion exercise. Before and after training, the patients’ metabolic responses were examined during the calf exercise test with phosphorus-31 nuclear magnetic resonance spectroscopy (31P-MRS) and calf blood flow with plethysmography. The new Borg scale was employed as a subjective fatigue scale. Results In a constant load exercise test (70% of maximum load achieved during the incremental exercise), standardised phosphocreatine and intracellular pH decreased less after training (p < 0.05, repeated measures analysis of variance). The new Borg scale improved significantly after training (p < 0.05). Blood flow did not change significantly in either test. Conclusions In patients with chronic heart failure, localised calf skeletal muscle training improved oxidative capacity without changes in calf blood flow. This training also improved the subjective fatigue scale. This training method may therefore alleviate leg fatigue experienced in daily activities.

Skeletal Muscle Metabolism in Maximal Bicycle and Treadmill Exercise Distinguished by Using In Vivo Metabolic Freeze Method and Phosphorus-31 Magnetic Resonance Spectroscopy in Normal Men

This study indicates that skeletal muscle metabolism may affect the results of maximal bicycle and treadmill exercise differently, and that maximal bicycle exercise was limited by quadriceps muscle metabolism rather than by cardiopulmonary capacity. In contrast, maximal treadmill exercise was not limited, eliciting more cardiopulmonary reserve and attaining greater peak oxygen uptake than maximal bicycle exercise.

Muscle high-energy metabolites and metabolic capacity in patients with heart failure.

UNLABELLED OKITA, K., K. YONEZAWA, H. NISHIJIMA, A. HANADA, T. NAGAI, T. MURAKAMI, and A. KITABATAKE. Muscle high-energy metabolites and metabolic capacity in patients with heart failure. Med Sci. Sports. Exerc., Vol. 33, No. 3, 2001, pp. 442-448. BACKGROUND Various abnormalities in skeletal muscle have been demonstrated by biopsy in patients with chronic heart failure (CHF). In mammalian muscles, high-energy metabolite composition at rest (HEMC) provides data on important metabolic characteristics; however, the significance of HEMC has not been clarified in patients with CHF. Therefore, we investigated HEMC in normal subjects and patients with CHF and examined its relation to muscle metabolic capacity and exercise tolerance. METHODS High-energy metabolites (phosphocreatine (PCr), inorganic phosphate (Pi), and ATP) in resting calf muscle were measured by 31P-magnetic resonance spectroscopy (31P-MRS), and ratios of Pi to PCr, Pi to ATP, and PCr to ATP were calculated in 34 patients with CHF and 13 age- and size-matched normal subjects. Muscle metabolism was evaluated during local exercise of unilateral plantar flexion by 31P-MRS. Metabolic capacity was estimated by the rate of PCr breakdown in relation to the workload. Systemic exercise capacity was evaluated by a bicycle ergometer. RESULTS The ratio of PCr to ATP was significantly increased in patients with CHF compared with controls (3.06 +/- 0.43 vs 2.72 +/- 0.36, P < 0.05) and was significantly correlated with metabolic capacity (r = -0.37, P < 0.01) and with peak oxygen uptake (r = -0.45, P < 0.01). There was a significant correlation between metabolic capacity and peak oxygen uptake (r = 0.53, P < 0.001). CONCLUSION HEMC was altered in patients with CHF, and this change was related to metabolic capacity and exercise capacity. These findings provide new insight into the mechanism of impaired muscle metabolism in CHF.

A 44-kDa of protein identical to the N-terminal amino acid sequence of MCT1 in human circulation

A family of specific carrier protein designated as monocarboxylate transporter (MCT) has been known to transport the lactate and other moncarboxylates in mammalian cells. We hypothesized the presence of serum protein in human circulation that may works as a lactate carrier and that biochemical structure would possesses common structure with MCT on the plasma membrane.Immunoblot analysis with an anti-MCT1 polyclonal antibody suggested the presence of a 44-kDa protein in human circulation and N-terminal amino acid sequencing exhibited a stretch of 14 amino acids which is completely identical to MCT1. The unbound fractions from the GST-MCT1 fusion protein-immobilized glutathione sepharose 4B column demonstrated that lactic acid concentration began to increase with one fraction delay compared to Sepharose 4B and GST-immobilized column. When lactic acid was washed away with PBS, lactic acid concentrations in the effuluent constantly decreased in both Sepharose 4B and GST-immobilized column. However, GST-MCT1-immobilized column showed specific convex curve from fraction approximately 3 mM of lactate and demonstrated wash out delay compared to Sepharose 4B and GST-immobilized column.These observations demonstrated biochemical and immunological similarities between a 44-kDa protein purified from human serum and MCT1 present on the plasma membrane. The studies on MCT1-fusion protein suggested possible functional properties of a 44-kDa protein as a lactate buffer by holding and unhand a lactate according to the lactate concentration in human blood. The experiments described herein have suggested the existence of lactate carrier in human circulation which is free from plasma membrane.

Skeletal muscle metabolism and oxygenation during post-exercise recovery in patients with chronic heart failure

Patients with chronic heart failure (CHF) are often limited in exercise and daily activities by muscle fatigue, which is attributed to intrinsic muscle abnormalities and/or impaired oxygen delivery. We investigated whether muscle oxygen kinetics would determine muscle metabolism during recovery after exercise. 8 patients with CHF (male, dilated cardiomyopathy, LVEF: 23.4_+12.4, NYHA: II-III)and age-matched 7