Chronic Heart Failure Clinical Trial
Official title:
Muscle Afferent Feedback Effects in Patients With Heart Failure: The Development of Central Fatigue
The purpose of the study is to find out more about the mechanism by which neural feedback from the working muscle affects the development of central fatigue during exercise. Subjects with chronic heart failure (HF) and healthy subject counterparts will be tested to determine the mechanisms accounting for the premature fatigue characterizing HF patients during physical activity.
A substantial part in limiting exercise and/or physical activity in humans results from the
development of peripheral and central fatigue during physical activity. Peripheral fatigue
comprises biochemical changes within the metabolic milieu of the working muscle leading to an
attenuated response to neural excitation, while central fatigue comprises a failure of the
central nervous system to drive motoneurons.
Patients with HF have overactive group III/IV muscle afferents and an exaggerated development
of central fatigue during physical activity that is not explained by their reduced physical
conditioning or cardiac insufficiency caused by their failing heart. The exact mechanisms
accounting for the exaggerated central fatigue in HF remains elusive, however, the
development of central fatigue during exercise has recently been linked to signaling by group
III/IV muscle afferents. This makes the heightened neural feedback in HF a likely candidate
for these patients' increased susceptibility to central fatigue.
Lower pH, increased lactate and increased adenosine triphosphate has been shown to activate
group III/IV afferents in a physiological manner and thus induce, in a rested and unfatigued
muscle, the intramuscular milieu associated with moderate to heavy exercise. The objective of
this study is to quantitate and compare the sensitivity of group III/IV afferents and
associated effects on central fatigue in HF patients and healthy controls when skeletal
muscle is subject to controlled lower pH, increased lactate and increased adenosine
triphosphate.
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