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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
8
Brock University
St. Catharines, Ontario, Canada
Resting motor threshold
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.
Time frame: Change from baseline 90-minutes
H-Reflex Amplitude
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.
Time frame: Change from baseline 90-minutes
Maximal Voluntary Contraction
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.
Time frame: Change from baseline 90-minutes
H-reflex latency
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.
Time frame: Change from baseline 90-minutes
Voluntary Activation
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.
Time frame: Change from baseline 90-minutes
Middle Cerebral Artery Blood Flow Velocity
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.
Time frame: Change from baseline 90-minutes
Brachial Artery Blood flow
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.
Time frame: Change from baseline 90-minutes
Internal Carotid Artery Blood Flow
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.
Time frame: Change from baseline 90-minutes
Blood pressure
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.
Time frame: Change from baseline 90-minutes
Pulse oximetry
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Change from baseline 90-minutes
Heart Rate
Heart rate will be measured by electrocardiogram. Heart rate will be quantified in beats per minute.
Time frame: Change from baseline 90-minutes
End-Tidal Gas Concentrations
The end-tidal concentrations of oxygen and carbon dioxide will be measured and reported in mmHg.
Time frame: Change from baseline 90-minutes