Alterations in contractility and intracellular Ca2+ transients in isolated bundles of skeletal muscle fibers from rats with chronic heart failure.

Abstract

To determine if chronic heart failure (CHF) leads to functional or structural alterations of skeletal muscle, we compared intracellular Ca2+ signaling, contractility, and the rate of fatigue development, together with electron microscopy (EM), in skeletal muscle preparations from rats with myocardial infarction-induced CHF versus sham-operated control rats. Bundles of 100 to 200 cells were dissected from the extensor digitorum longus (EDL) muscle of control (n = 13) and CHF (n = 19) rats and were either loaded with aequorin or fixed for EM. Muscles from CHF rats exhibited depressed tension development compared with control muscles during twitches (1.4 +/- 0.2 versus 2.8 +/- 0.7 g/mm2, P < .05) and maximal tetani (5.3 +/- 1.4 versus 10.7 +/- 2.4 g/mm2, P < .05). Depressed tension in CHF was accompanied by reduced quantitative [Ca2+]i release during twitches (0.7 +/- 0.1 versus 0.4 +/- 0.1 microM, P < .05) and during maximal tetani (1.8 +/- 0.3 versus 0.9 +/- 0.2 microM, P < .05). Skeletal muscle from CHF rats also demonstrated prolonged intracellular Ca2+ transients during twitches and tetani and accelerated fatigue development. EM revealed a lack of cellular atrophy in the CHF rats. In conclusion, EDL skeletal muscle from rats with CHF had intrinsic abnormalities in excitation-contraction coupling unrelated to cellular atrophy. These findings indicate that CHF is a condition accompanied by EDL skeletal muscle dysfunction.

Skeletal muscle contractile protein function is preserved in human heart failure

“…This contractile deficit at the whole muscle level has been observed in isolated muscle tissue in animal models (16,21) and in chemically skinned, single muscle fibers in humans (26), suggesting that the heart failure syndrome promotes contractile dysfunction at the level of the myofilaments. In the present study, we investigated the role of individual myofilament components in the decreased skeletal muscle function of heart failure patients.…”

“…thin filament; myosin; fiber type EXERCISE INTOLERANCE IS A hallmark symptom of chronic heart failure (CHF). Although cardiac pump dysfunction can limit exercise capacity, research conducted over the last two decades has highlighted the importance of changes in the skeletal musculature in heart failure (10,21,37). Recent studies have shown that skeletal muscle strength is reduced in heart failure and that this decrement cannot be solely accounted for by a reduction in muscle mass (9,28), suggesting a fundamental defect in skeletal muscle contractile function.…”

Aerobic exercise training in heart failure: impact on sympathetic hyperactivity and cardiac and skeletal muscle function

“…Alterations in excitation-contraction coupling and protein synthesis/degradation balance have also been proposed to contribute to skeletal muscle fatigability and weakness in HF (Figure 3). In severe HF rats, decreased skeletal muscle sarcoplasmic Ca 2+ levels were associated with a reduced rate of sarcoplasmic reticulum Ca 2+ release (58) and reuptake (59). This response is partially explained by reduced expression of proteins involved in intracellular Ca 2+ homeostasis in skeletal muscles consisting of different fiber types such as soleus and plantaris muscles (predominantly oxidative and glycolytic muscles, respectively) (23).…”

Relevância e tratamento das lesões características da insuficiência cardíaca na musculatura esquelética

“…27 Muito tempo se passou e em 1993 chegou-se à conclusão que a diminuição na produção de força máxima dos pacientes com insuficiência cardíaca persiste mesmo quando as forças são normalizadas pela massa muscular úmida e/ou pela área de secção transversa do músculo. 28 Além disso, as anormalidades supracitadas, como atrofia, mudança do tipo de fibra e menor prevalência do metabolismo aeróbio, não são prováveis de explicar completamente o padrão de fadiga muscular dos pacientes, que devido à sua velocidade e gravidade parece refletir prejuízo no acoplamento excitação-contração 16,[29][30][31] , que está diretamente relacionado ao íon Ca 2+ .…”

“…Após Perreault et al (1993) 28 encontrarem prejuízo no transiente de Ca 2+ na insuficiência cardíaca na musculatura esquelética em 1993, começaram a ser estudadas a expressão das proteínas que transportam esse íon em diferentes etiologias e níveis de gravidade de insuficiência cardíaca, porém os estudos ainda são muito escassos. O trabalho supracitado foi o primeiro a relatar redução na magnitude e na velocidade da captação de Ca 2+ pelo retículo sarcoplasmá-tico após a contração em associação com redução na tensão e na força tetânica no músculo extensor longo dos dedos de ratos com insuficiência cardíaca.…”