Eight Days of Mild Intermittent Hypoxia Improves Mitochondrial Capacity and Autonomic Dysfunction in Individuals Living with Incomplete Spinal Cord Injury

Research Objectives: To investigate the effects of mild intermittent hypoxia (MIH) on mitochondrial capacity at rest, oxygen extraction during hypoxia, and autonomic dysfunction in individuals with motor incomplete spinal cord injury (iSCI).

Design: 2-arm parallel design.

Setting: Research Laboratory.

Participants: Four individuals with motor iSCI (C4, C7/T5, C5, C4/C7) aged 46 ± 1.4 (3 Males, 1 Female).

Interventions: Eight days of MIH consisting of twelve two-minute bouts of hypoxia interspersed with two minutes of normoxic recovery. Slight hypercapnia (+3 mmHg) was maintained throughout.

Main Outcome Measures: A full thigh arterial occlusion is administered with a tourniquet inflated to 300 mmHg. During occlusion and hypoxia, a near infrared spectroscopy device is used to measure muscle oxygen saturation of the lateral gastrocnemius muscle of dominant leg. The amplitude of oxygen extraction during occlusion is a measure of mitochondrial capacity. During hypoxia, the amplitude desaturation, compared to normoxia, was calculated for the first, second, eleventh, and twelfth hypoxic bouts as a measure of oxygen extraction. The first two and last two hypoxic bouts were then averaged (i.e., initial and final). Systolic and diastolic blood pressure (SBP & DBP) responses are obtained during occlusion and a sit-up test for assessing autonomic dysreflexia (AD) and orthostatic hypotension (OH), respectively.

Results: Mitochondrial extraction improved from 55 ± 10% to 89 ± 9% after 8 days of MIH (p = 0.07). On day 1, oxygen extraction increased from 4.70 ± 1.62 to 4.78 ± 2.14%, respectively. On day 8, the amplitude of oxygen extraction was 2.94 ± 1.25% and 3.55% ± 0.76% during initial and final bouts, respectively. Notably, on day 8, the amplitude in oxygen extraction was lower across all bouts compared to day 1. However, the amplitude changes from initial to final bouts were smaller on day 1 (17 ± 29%) than day 8 (56 ± 42%). After the 8-day MIH, SBP and DBP changes during AD improved by 44 ± 8% (p < 0.01) and 43 ± 5% (p = 0.01) as OH improved by 88 ± 21% (p = 0.01) and 128 ± 50% (p = 0.02).

Conclusions: Eight days of MIH improved mitochondrial capacity coupled with the reduced oxygen extraction during hypoxia on day 8, suggests an increased oxygen reserve. Likewise, these improvements in mitochondrial function were concurrent with improvements in AD and OH, suggesting that mitochondrial function may be a potential mechanism impacting autonomic function.

Author(s) Disclosures: None