William Zev Rymer, Shirley Ryan Ability Lab/Northwestern University, Chicago, USA

Therapeutic actions of acute intermittent hypoxia

Funded in: 2021, 2022, 2023

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Problem: Reduction in oxygen concentration (hypoxia) in the inspired air has surprising therapeutic benefits
Target: Determine relation between hypoxia and muscle strength
Goal: Use hypoxia as a therapeutic tool

Over the last ten years, the research team has shown that rapid reductions in oxygen concentration in the inspired air has surprising therapeutic benefits for persons with incomplete spinal cord injury.

In particular, the scientists have demonstrated that a sequence of 15 brief episodes in which oxygen concentration in the inspired air is reduced to 10% is able to produce rapid changes in muscle voluntary strength. The effect occurs already within 30 minutes of completing a hypoxia sequence. This increase in strength has been demonstrated in muscles of the lower extremity at the ankle and in the upper extremity in both the hands and elbow muscles. These effects of hypoxia are substantial, they last for several hours and may even be detectable the following day.

The scientists are presently testing the potential value of brief hypoxia episodes (AIH) in promoting long-term functional recovery of patients with incomplete spinal injury. However, the researchers do not know exactly how this intervention works in man.

Accordingly, the objective of this proposal is to examine three hypotheses about hypoxia action:

1. AIH improves neuromuscular transmission between motor nerve axons and muscle fibers.

2. AIH induces an increase in excitability of spinal motor neurons making them more accessible to descending voluntary commands from brain. This could result in an increase in voluntary strength.

3. AIH promotes increased recruitment and higher firing rates of certain motor neurons. These units will be recorded using novel high-density EMG grids placed over the major muscles, and advanced decomposition software.

By systematically examining each of these hypotheses the scientists should be able to determine which factors are primarily responsible for increases in muscle strength. This should help them to optimize ways in which the researchers use hypoxia as a therapeutic tool.