Premature Fatigue in Veterans With Heart Failure: Neuronal Influences
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 20 - 75 |
| Updated: | 5/11/2017 |
| Start Date: | July 1, 2015 |
| End Date: | March 15, 2017 |
A hallmark of patients with heart failure (HF) is premature fatigue which impairs their
quality of life and depicts a major source of morbidity. Premature fatigue may be attributed
to a) contraction-induced transient changes within muscles (i.e. peripheral fatigue) and/or
b) failure of the central nervous system to 'drive' / activate locomotor muscles (i.e.
central fatigue). Both determinants of fatigue can lead to a reduction in a muscle's force
and power generating capacity and to a compromised ability to perform whole body activities
(e.g. walking). Recent findings in health have documented that group III/IV afferent fibers
from the working muscle play a critical role in the development of both components of
fatigue. Specifically, group III/IV muscle afferents limit central motor drive (CMD) during
exercise and thereby exaggerate the development of central fatigue. In contrast, muscle
afferents optimize muscle O2 delivery through the precise regulation of circulation and
ventilation during exercise and thereby attenuate the development of peripheral fatigue.
quality of life and depicts a major source of morbidity. Premature fatigue may be attributed
to a) contraction-induced transient changes within muscles (i.e. peripheral fatigue) and/or
b) failure of the central nervous system to 'drive' / activate locomotor muscles (i.e.
central fatigue). Both determinants of fatigue can lead to a reduction in a muscle's force
and power generating capacity and to a compromised ability to perform whole body activities
(e.g. walking). Recent findings in health have documented that group III/IV afferent fibers
from the working muscle play a critical role in the development of both components of
fatigue. Specifically, group III/IV muscle afferents limit central motor drive (CMD) during
exercise and thereby exaggerate the development of central fatigue. In contrast, muscle
afferents optimize muscle O2 delivery through the precise regulation of circulation and
ventilation during exercise and thereby attenuate the development of peripheral fatigue.
Recent findings in HF suggest an altered effect of group III/IV muscle afferents in this
population. Although normal afferent feedback is crucial for adequate O2 delivery during
exercise, excessive neural feedback has substantial negative consequences. HF patients are
characterized by augmented neural feedback arising from overactive muscle afferents. It has
been hypothesized that this abnormality compromises locomotor muscle O2 delivery in these
patients. Therefore, the abnormally elevated muscle afferent feedback in HF might
exacerbate, compared to healthy age- and activity matched individuals (CTRLs), the
development of both peripheral (via limiting O2 delivery) and central (via restricting CMD)
fatigue during exercise. Recent advances in non-invasive stimulation techniques offer a
genuine opportunity to identify the sites and synaptic mechanisms that mediate central and
peripheral fatigue including alterations in the responsiveness of the corticospinal tract
(i.e. a determinant of central fatigue). Taken together, the proposed studies aim to
determine the impact of HF on the precise development of central and peripheral fatigue
during both whole body and single muscle exercise and evaluate the extent to which group
III/IV muscle afferents contribute to this development.
population. Although normal afferent feedback is crucial for adequate O2 delivery during
exercise, excessive neural feedback has substantial negative consequences. HF patients are
characterized by augmented neural feedback arising from overactive muscle afferents. It has
been hypothesized that this abnormality compromises locomotor muscle O2 delivery in these
patients. Therefore, the abnormally elevated muscle afferent feedback in HF might
exacerbate, compared to healthy age- and activity matched individuals (CTRLs), the
development of both peripheral (via limiting O2 delivery) and central (via restricting CMD)
fatigue during exercise. Recent advances in non-invasive stimulation techniques offer a
genuine opportunity to identify the sites and synaptic mechanisms that mediate central and
peripheral fatigue including alterations in the responsiveness of the corticospinal tract
(i.e. a determinant of central fatigue). Taken together, the proposed studies aim to
determine the impact of HF on the precise development of central and peripheral fatigue
during both whole body and single muscle exercise and evaluate the extent to which group
III/IV muscle afferents contribute to this development.
Inclusion Criteria:
- subjects with a history of stable cardiomyopathy (ischemic and non-ischemic, >1yr
duration, ages 20-75 yr),
- not pacemaker dependent (no biventricular pacers),
- NYHA class II and III symptoms,
- Left ventricular ejection fraction (LVEF)<35%,
- no or minimal smoking history (<15 pk yrs) and on stable medications.
- The investigators will also study subjects with preserved ejection fraction
- heart failure with a preserved ejection fraction (HFpEF);
- LVEF >50%,
- >1yr duration,
- ages 20-75 yr,
- not pacemaker dependent,
- NYHA class II and III symptoms,
- no or minimal smoking history (<15 pk yrs) and on stable medications. The
investigators will exclude morbidly obese patients (BMI >35), patients with
uncontrolled hypertension (>160/100), anemia (Hgb<9) and severe renal insufficiency
(individuals with creatinine clearance <30 by the Cockcroft-Gault formula).
Exclusion Criteria:
- Patients with significant non-cardiac comorbidities, which if present could alter the
study results, will be excluded.
- Patients will be sedentary, defined here as no regular physical activity for at least
the prior 6 months and current activity level will be documented by an activity
questionnaire.
- Candidates must have no orthopedic limitations that would prohibit them from
performing exercise.
- Due to the typical age of patients with heart failure, all women will be
postmenopausal (either natural or surgical) defined as a cessation of menses for at
least 2 years,
- and in women without a uterus, follicle stimulating hormone (FSH) >40 IU/L.
- Women currently taking hormone replacement therapy (HRT) will be excluded from the
proposed studies due to the direct vascular effects of HRT.
- Patients with a pacemaker and / or defibrillator will be excluded from the study due
to the use of a magnetic/electric stimulators.
We found this trial at
1
site
Salt Lake City, Utah 84148
Principal Investigator: Markus Amann, PhD
Phone: 801-582-1565
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