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Recently, direct evidences point to the contributing role of peripheral muscle fatigue in exercise tolerance among patients with COPD. However, the physiological mechanisms by which peripheral muscle fatigue impairs exercise tolerance are still unknown, as factors regulating peripheral muscle fatigue in COPD may be complex. One possible link between limb muscle fatigue and exercise intolerance could be enhanced afferent signals from the active limb muscles to the central command, thereby limiting central motor output and eventually leading to exercise termination.
A direct method to investigate the regulation of peripheral muscle fatigue during exercise in patients with COPD is the blockade of peripheral neural afferents via lumbar anesthesia. Consequently, investigating the interplay between the peripheral muscular component and the central motor command during self-paced exercise could shed light on the regulation of peripheral muscle fatigue in COPD and its implication in exercise intolerance.
The aim of the study is to characterize the role of peripheral muscle afferents on the development of muscle fatigue, cardiorespiratory response and exercise tolerance to constant-workrate endurance cycling exercise in patients with COPD.
In a double-blind randomized design, patients with GOLD stage II-III COPD will be recruited and will complete a constant-workrate cycling test following either the injection of a placebo [NaCl, interspinous L2-L3] or an opioid [Fentanyl 25 µg, intrathecal L2-L3] inhibiting central feedback of peripheral muscles sensory afferents. Quadriceps force (TwQ) will be measured by magnetic stimulation of the femoral nerve and central chemoreceptors response will be assessed by CO2 rebreathing, both performed before and after the injection. Finally, TwQ will also be measured after the endurance cycling test to assess the magnitude of quadriceps fatigue induced by symptom-limited exercise.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fentanyl | Experimental |
| |
| Placebo | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fentanyl | Drug | Single-dose of intrathecal fentanyl [25ug] Duration of fentanyl : 3.5 hours |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Endurance time | Exercise tolerance is referred as the endurance time (sec) during constant-workrate cycling test at 80 % of the predetermined maximal workload in every conditions (placebo and fentanyl) | 60-min post-anesthesia - From the start to the end of the constant-workload cycling test (limited by symptoms of the patients) |
| Measure | Description | Time Frame |
|---|---|---|
| Ventilatory response | The ventilatory response (Ventilation, L/min) will be monitored continuously during the cycling test and will be compared between the two conditions (placebo vs. fentanyl) | 60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| François Maltais, MD | Institut universitaire de cardiologie et de pneumologie de Québec, University Laval | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval | Québec | Quebec | G1V 4G5 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22822019 | Derived | Gagnon P, Bussieres JS, Ribeiro F, Gagnon SL, Saey D, Gagne N, Provencher S, Maltais F. Influences of spinal anesthesia on exercise tolerance in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012 Oct 1;186(7):606-15. doi: 10.1164/rccm.201203-0404OC. Epub 2012 Jul 19. |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D053120 | Respiratory Aspiration |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D005283 | Fentanyl |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo comparator |
| Drug |
placebo [NaCl] |
|
| Quadriceps muscle fatigue |
The quadriceps muscle fatigue will be monitored before and after the cycling test to quantify the extent of muscle fatigue produced by the cycling test. This will be done by magnetic stimulation of the femoral nerve and maximal voluntary contraction. Also, non-invasive surface electromyography (EMG) of the quadriceps will help to better characterize muscle fatigue. |
| 15-min after the end of constant-workload cycling test |
| Dynamic hyperinflation | Dynamic hyperinflation will be monitored periodically every 2-min during the cycling test by manoeuvres of inspiratory capacity and will be compared between the two conditions (placebo vs. fentanyl) | 60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients) - Every 2-min during exercise |
| Effort perception | Leg fatigue and dyspnea perception (Borg scale scores) will be monitored periodically every 2-min during the cycling test and will be compared between the two conditions (placebo vs. fentanyl) | 60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients) - Every 2-min during exercise |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012120 | Respiration Disorders |