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

Abstract

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

Two-arm parallel design.

Setting

Research Laboratory.

Participants

Four individuals with motor iSCI (C4, C7/T5, C5, and C4/C7) aged 46±1.4 years (3 males, 1 female).

Interventions

Eight days of MIH consisting of twelve 2-minute bouts of hypoxia interspersed with 2 minutes of normoxic recovery. Slight hypercapnia (+3mmHg) 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 with normoxia, was calculated for the 1st, 2nd, 11th, and 12th hypoxic bouts as a measure of oxygen extraction. The first 2 and last 2 hypoxic bouts were then averaged (ie, initial and final). Systolic and diastolic blood pressure 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=.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 with 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, systolic blood pressure and diastolic blood pressure changes during AD improved by 44%±8% (P<.01) and 43%±5% (P=.01) as OH improved by 88%±21% (P=.01) and 128±50% (P=.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.

Disclosures

none.