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Cerebral Blood Flow and PETCO2 on Neuromuscular Function During Environmental Stress

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ClinicalTrials.gov Identifier: NCT01830335
Recruitment Status : Completed
First Posted : April 12, 2013
Last Update Posted : January 29, 2018
Sponsor:
Information provided by (Responsible Party):
Stephen Cheung, Brock University

Brief Summary:

Environmental stress, such as low oxygen availability (hypoxia), has been associated with impaired neuromuscular performance; however, the mechanisms associated with these performance decrements remain unclear. While the majority of research suggests that the observed fatigue is related to the central nervous system, the influence of changes in cerebral blood flow (CBF) and associated changes in cerebral pH (partial pressure of carbon dioxide; PCO2) remains unexamined. In response to hypoxic stress, humans hyperventilate to maintain oxygen consumption, resulting in a hypocapnia mediated decrease in CBF and cerebral alkalosis (decreased PCO2). Previous research suggests that hyperventilation induces changes in neural excitability and synaptic transmission; however, it remains unclear if these changes are related to hypocapnia mediated decrease in CBF or cerebral alkalosis or both.

The purpose of the proposed research program is to examine the influence of changes in CBF and cerebral alkalosis on neuromuscular function during environmental stress. The research program will consist of 2 separate projects, summarized below in a table outlining the proposed protocols and resultant physiological manipulations. During each manipulation, neuromuscular function will be evaluated and compared to baseline (normoxic) conditions using a repeated measures design.

The research program will consist of 2 separate projects. Project 1 will examine the changes in CBF and alkalosis by using (a) indomethacin (decrease CBF; no change PCO2) and (b) hypocapnia (decrease CBF; decrease PCO2). Using a similar experimental design, Project 2 will examine the change in CBF and alkalosis during hypoxia by using (a) poikilocapnic hypoxia (decrease PO2; decrease CBF; decrease PCO2), (b) isocapnic hypoxia (decrease PO2; no change CBF; no change PCO2) and (c) isocapnic hypoxia + indomethacin (decrease PO2; decrease CBF; no change PCO2). During each manipulation, neuromuscular function will be evaluated and compared to baseline (normoxic) conditions using a repeated measures design.

Therefore, Project 1 will examine the separate and combined effect of changes in CBF and cerebral alkalosis on neuromuscular function independent of environmental manipulations. Subsequently, Project 2 will examine neuromuscular function during hypoxia while controlling CBF and cerebral alkalosis. It is hypothesized that changes in PCO2 and therefore, changes in cerebral alkalosis will contribute to neuromuscular fatigue independent of changes in CBF and oxygen availability.


Condition or disease Intervention/treatment Phase
Healthy Males Neuromuscular Function Drug: Indomethacin Drug: Placebo Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: The Influence of Cerebral Blood Flow and Alkalosis on Neuromuscular Function During Environmental Stress
Study Start Date : April 2013
Actual Primary Completion Date : June 2015
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Drug
Indomethacin 1.2 mg kg 1 dose
Drug: Indomethacin
Placebo Comparator: Placebo
flour capsule
Drug: Placebo



Primary Outcome Measures :
  1. Resting motor threshold [ Time Frame: Change from baseline 90-minutes ]
    Motor evoked potentials are recorded from muscles following transcranial magnetic stimulation of motor cortex. The resting motor threshold is defined as the minimum stimulation intensity required to elicit a motor evoked potential. Resting motor threshold will be quantified in millivolts.

  2. H-Reflex Amplitude [ Time Frame: Change from baseline 90-minutes ]
    The H-Reflex is an indirect measure of motor neuron excitability. Initially, a maximal M-wave (M-max) will be elicited by stimulating (1 ms in duration; 15 s between stimuli) the median nerve incrementally (2 V increments) until the largest waveform is observed. The peak-to-peak amplitude of this waveform is considered M-max. Using similar procedures as above, a sub-maximal M-wave of 5% M-max will be elicited and the amplitude of the resultant H-reflex (a small waveform observed following the submaximal M-wave) will be calculated. The amplitude of the H-reflex will be quantified in milllivolts.

  3. Maximal Voluntary Contraction [ Time Frame: Change from baseline 90-minutes ]
    During maximal voluntary contraction (MVC) testing, the participants' right arm will be secured in a custom made device used to isolate forearm flexion and to measure force production by the flexor carpi radialis muscle. Participants will be asked to produce a 5-second MVC and will be verbally encouraged to maintain maximal force production throughout the duration of the contraction. MVC will be quantified as the maximum force production in newton meters.

  4. H-reflex latency [ Time Frame: Change from baseline 90-minutes ]
    The H-Reflex is an indirect measure of motor neuron excitability. Initially, a maximal M-wave (M-max) will be elicited by stimulating (1 ms in duration; 15 s between stimuli) the median nerve incrementally (2 V increments) until the largest waveform is observed. The peak-to-peak amplitude of this waveform is considered M-max. Using similar procedures as above, a sub-maximal M-wave of 5% M-max will be elicited and the amplitude of the resultant H-reflex (a small waveform observed following the submaximal M-wave) will be calculated. The onset latency of the H-reflex will be quantified in milliseconds.

  5. Voluntary Activation [ Time Frame: Change from baseline 90-minutes ]
    The level of neural drive to muscle during contraction is termed voluntary activation and will be estimated by interpolation of a single supramaximal motor evoked potential during the 5-second MVC contraction. If extra force is evoked by the 'superimposed' stimulus then either the stimulated axons were not all recruited voluntarily or they were discharging at sub-tetanic rates. Therefore, voluntary activation will be quantified as the amplitude of maximal voluntary force production, relative to the amplitude of the supramaximal MEP.


Secondary Outcome Measures :
  1. Middle Cerebral Artery Blood Flow Velocity [ Time Frame: Change from baseline 90-minutes ]
    Middle cerebral artery (MCA) blood flow velocity will be measured non-invasively by a 2-MHz transcranial Doppler (TCD) ultrasound probe, attached bilaterally to a comfortable headband and secured anterior to the zygomatic arch, rostral of the pinna. Doppler probes will be paced over the temporal windows (near the ear) and will remain in place throughout the duration of the experimental protocol. MCA velocity will be quantified in cm/s.

  2. Brachial Artery Blood flow [ Time Frame: Change from baseline 90-minutes ]
    Brachial artery blood flow will be measured non-invasively using a high-resolution ultrasound machine. Participants will lie supine with their forearm extended in a comfortable position. Blood flow measurements will be taken in the top 1/3 of the upper arm over the duration of 10 cardiac cycles (approximately 60 seconds). Blood flow will be quantified in L/min.

  3. Internal Carotid Artery Blood Flow [ Time Frame: Change from baseline 90-minutes ]
    Internal carotid artery (ICA) blood flow will be measured non-invasively using a high-resolution ultrasound machine. Participants will lie supine with a slight extension of the neck and at 45° of lateral flexion away from the side being scanned. ICA measurements will be taken 1 cm superior to the common carotid bifurcation over the duration of 10 cardiac cycles (approximately 60 seconds). Blood flow will be quantified in L/min.

  4. Blood pressure [ Time Frame: Change from baseline 90-minutes ]
    Beat by beat blood pressure will be calculated from the blood pressure waveform using finger photoplethysmography (Nexfin, bmeye), with a finger cuff placed directly over the middle finger on the left hand. Blood pressure will be quantified in mmHg.

  5. Pulse oximetry [ Time Frame: Change from baseline 90-minutes ]
    A pulse oximetry probe will be placed over a finger to provide a continuous, non-invasive measurement of the blood oxygen saturation to confirm that the end-tidal forcing system is controlling oxygen delivery at the desired levels during each experiment. Oxygen saturation will be quantified as a percentage.

  6. Heart Rate [ Time Frame: Change from baseline 90-minutes ]
    Heart rate will be measured by electrocardiogram. Heart rate will be quantified in beats per minute.

  7. End-Tidal Gas Concentrations [ Time Frame: Change from baseline 90-minutes ]
    The end-tidal concentrations of oxygen and carbon dioxide will be measured and reported in mmHg.



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Ages Eligible for Study:   18 Years to 25 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18 to 25 yrs old; healthy males

Exclusion Criteria:

  • diagnosed medical condition; NSAID allergy; smoker; high altitude exposure; implants

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01830335


Locations
Canada, Ontario
Brock University
St Catharines, Ontario, Canada, L2S 3A1
Sponsors and Collaborators
Brock University
Investigators
Principal Investigator: Stephen Cheung, PhD Brock University

Responsible Party: Stephen Cheung, Professor, Brock University
ClinicalTrials.gov Identifier: NCT01830335     History of Changes
Other Study ID Numbers: 12-167
First Posted: April 12, 2013    Key Record Dates
Last Update Posted: January 29, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Indomethacin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gout Suppressants
Tocolytic Agents
Reproductive Control Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action