Cerebral Blood Flow and PETCO2 on Neuromuscular Function During Environmental Stress
Condition: Healthy Males; Neuromuscular Function
Study type: Interventional
Phase: Phase 4

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.
    


Intervention name(s): Indomethacin; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Indomethacin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Basic Science