Temperature-dependent skeletal muscle dysfunction in rats with congestive heart failure

Area of Science:

• Physiology
• Cardiovascular Research
• Muscle Biology

Background:

• Slow-twitch muscle dysfunction, characterized by reduced force and increased fatigue, is a hallmark of congestive heart failure (CHF).
• The precise mechanisms underlying these muscle abnormalities, particularly within the excitation-contraction coupling process, remain unclear.
• Altered temperature sensitivity of muscle contractile properties has been observed in CHF, prompting investigation into its underlying causes.

Purpose of the Study:

• To investigate the hypothesis that temperature sensitivity of soleus muscle contractile properties is altered in congestive heart failure (CHF) rats.
• To determine if alterations in the temperature sensitivity of intracellular calcium (Ca2+) handling contribute to muscle dysfunction in CHF.
• To elucidate the molecular basis of slow-twitch muscle dysfunction in CHF by examining excitation-contraction coupling.

Main Methods:

• Electrical stimulation of the in situ soleus muscle in rats with 6-week postinfarction CHF and sham controls at varying frequencies (1, 50 Hz) and temperatures (35, 37, 40°C).
• Application of a fatigue protocol (5-Hz stimulation for 30 min) at different temperatures to assess force development and rates of contraction/relaxation.
• Measurement of Ca2+ uptake and release rates in sarcoplasmic reticulum vesicles across a range of temperatures.

Main Results:

• Soleus muscle contraction and relaxation rates were slower in CHF rats at 35°C, but this difference diminished at 40°C.
• Force development exhibited greater temperature sensitivity in CHF rats compared to controls.
• Contraction and relaxation rates were less temperature sensitive in CHF rats than in sham controls.
• No correlation was found between Ca2+ uptake/release rates in vesicles and the observed differences in contractile properties or temperature sensitivity between CHF and sham groups.

Conclusions:

• The temperature sensitivity of slow-twitch muscle contraction and relaxation is altered in a rat model of congestive heart failure (CHF).
• The observed muscle dysfunction in CHF is not attributable to alterations in the temperature sensitivity of intracellular calcium (Ca2+) cycling.
• These findings suggest that molecular mechanisms beyond intracellular Ca2+ handling are responsible for slow-twitch muscle abnormalities in CHF.