Skeletal muscle metabolism in the leg during exercise in patients with congestive heart failure

1990 ◽  
Vol 78 (5) ◽  
pp. 515-519 ◽  
Author(s):  
Pierre-Yves Marie ◽  
Jean-Marie Escanye ◽  
François Brunotte ◽  
Brigitte Robin ◽  
Paul Walker ◽  
...  

1. Using 31P nuclear magnetic resonance, it has previously been demonstrated that patients with congestive heart failure exhibit a greater than normal phosphocreatine (PCr) depletion in the working skeletal muscles of the arm. We have studied the importance of the work necessary to reach a similar PCr depletion {[PCr]/([PCr] + [Pi]) = 0.5} in calf muscle. Our results show significantly lower values for patients with congestive heart failure in both aerobic and ischaemic conditions (respectively: 0.009 ± 0.007 vs 0.026 ± 0.013 W/kg body weight, P <0.01; 0.29 ± 0.16 vs 0.90 ± 0.25 J/kg body weight, P <0.01). 2. This original model of skeletal muscle exercise facilitates a comparison of PCr recovery rate due to a similarity in the PCr depletion and intracellular pH in the two series at the start of recovery. However, the PCr recovery rate is similar after both normoxic and ischaemic exercise, i.e. respective percentages of PCr increase in the first 25 s recovery spectrum were: (a) aerobic exercise, congestive heart failure 133 ± 18%, control series 138 ± 18%; (b) ischaemic exercise, congestive heart failure 114 ± 13%, control series 118 ± 12%. The absence of a difference in PCr recovery rate and the greater PCr depletion by ischaemic work in patients with congestive heart failure suggest modifications that cannot be explained by a reduced blood flow to the muscle. 3. When comparing the two series, intracellular pH evolved similarly in normoxia and ischaemia during both work and recovery. Thus, no increase in anaerobic glycolytic activity appears when equivalent PCr depletion has occurred.

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Valentina Sala ◽  
Stefano Gatti ◽  
Simona Gallo ◽  
Enzo Medico ◽  
Daniela Cantarella ◽  
...  

Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level.


Circulation ◽  
1987 ◽  
Vol 76 (5) ◽  
pp. 1009-1019 ◽  
Author(s):  
B Massie ◽  
M Conway ◽  
R Yonge ◽  
S Frostick ◽  
J Ledingham ◽  
...  

2005 ◽  
Vol 289 (2) ◽  
pp. R389-R394 ◽  
Author(s):  
Hanne M. Schiøtz Thorud ◽  
Annicke Stranda ◽  
Jon-Arne Birkeland ◽  
Per K. Lunde ◽  
Ivar Sjaastad ◽  
...  

Patients with congestive heart failure (CHF) are prone to increased skeletal muscle fatigue. Elevated circulatory concentrations of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein-1, which may stimulate matrix metalloproteinase (MMP) activity and, thereby, contribute to skeletal muscle dysfunction, are frequently found in CHF. However, whether skeletal muscle MMP activity is altered in CHF is unknown. Hence, we have used a gelatinase assay to assess the activity of MMP and tissue inhibitors of MMP in single skeletal muscles of rats with CHF 6 wk after induction of myocardial infarction. Sham-operated (Sham) rats were used as controls. We also measured the gene expression and protein contents of MMP-2 and MMP-9 in skeletal muscles of these rats. Plasma MMP activity was nearly seven times higher ( P < 0.05) in CHF than in Sham rats. Concomitantly, the MMP activity within single slow- and fast-twitch skeletal muscles of CHF rats increased two- to fourfold compared with Sham animals, whereas tissue inhibitor of MMP activity did not differ ( P > 0.05). Preformed MMP-2 and MMP-9 were probably activated in CHF, because neither their gene expression nor protein levels were altered ( P > 0.05). Serum concentrations of TNF-α and monocyte chemoattractant protein-1 remained unchanged ( P > 0.05) between CHF and Sham rats during the 6-wk observation period. We conclude that development of CHF in rats enhances MMP activity, which in turn may distort the normal contractile function of skeletal muscle, thereby contributing to increased skeletal muscle fatigue.


1990 ◽  
Vol 65 (16) ◽  
pp. 1121-1126 ◽  
Author(s):  
Donna M. Mancini ◽  
Mitchell Schwartz ◽  
Nancy Ferraro ◽  
Richard Seestedt ◽  
Britton Chance ◽  
...  

2002 ◽  
Vol 283 (3) ◽  
pp. C802-C810 ◽  
Author(s):  
Giorgio Vescovo ◽  
Barbara Ravara ◽  
Valerio Gobbo ◽  
Marco Sandri ◽  
Annalisa Angelini ◽  
...  

Skeletal muscle in congestive heart failure is responsible for increased fatigability and decreased exercise capacity. A specific myopathy with increased expression of fast-type myosins, myocyte atrophy, secondary to myocyte apoptosis triggered by high levels of circulating tumor necrosis factor-α (TNF-α) has been described. In an animal model of heart failure, the monocrotaline-treated rat, we have observed an increase of apoptotic skeletal muscle nuclei. Proapoptotic agents, caspase-3 and -9, were increased, as well as serum levels of TNF-α and its second messenger sphingosine. Treatment of rats withl-carnitine, known for its protective effect on muscle metabolism injuries, was found to inhibit caspases and to decrease the levels of TNF-α and sphingosine, as well as the number of apoptotic myonuclei. Staurosporine was used in in vitro experiments to induce apoptosis in skeletal muscle cells in culture. Whenl-carnitine was applied to skeletal muscle cells, before staurosporine treatment, we observed a reduction in apoptosis. These findings show that l-carnitine can prevent apoptosis of skeletal muscles cells and has a role in the treatment of congestive heart failure-associated myopathy.


Sign in / Sign up

Export Citation Format

Share Document