Daily intermittent hypoxia enhances walking after chronic spinal cord injury

Abstract

Objectives:To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI).Methods:Nineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349).Results:dAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1–6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9–6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5–171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1–173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3–134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6–173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3–206.6 m, p < 0.001).Conclusions:dAIH ± walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI.Classification of evidence:This study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI.

Enhanced Retinal Ganglion Cell Survival in Glaucoma by Hypoxic Postconditioning After Disease Onset

“…Given that the progressive RGC injury occurring in glaucoma is characterized by a multifactorial pathology putatively involving a host of excitotoxic, inflammatory, immune, vascular, biomechanical, and other factors [58][59][60], and that the mechanisms dictating RGC soma and RGC axon loss may be quite distinct [61][62][63], the epigenetic changes induced by RH-Post will likely be extensive in order to account for the magnitude of the protection achieved. It is also worth noting that, although exposures to intermittent systemic hypoxia may not ultimately be adopted as a clinical treatment for glaucoma patients, this very stimulus has established a strong record for protection against a variety of acute and chronic diseases in the CNS [27][28][29][30][64][65][66][67], and other tissues [68][69][70], and may not be easily mimicked by a pharmacologic, monotherapy approach.…”

A Systematic Review of Experimental Strategies Aimed at Improving Motor Function after Acute and Chronic Spinal Cord Injury

“…52 Using a double-blind, randomized crossover study, Daih (15-90 sec intervals, fraction of inspired oxygen = 0.9 for 5 days) or Daih-Sham were delivered in isolation or combined with subsequent walking training, in 19 persons with incomplete SCI. 52 The authors found that Daih increased walking speed (measured by the 6-min walk) 1 day and 2 weeks post-administration. Further, the combination of Daih and walking training was associated with greater improvements in walking endurance (measured by the 10-meter walk) than walking training alone and Daih alone at 5 days and 1 week post-administration.…”

“…Further, the combination of Daih and walking training was associated with greater improvements in walking endurance (measured by the 10-meter walk) than walking training alone and Daih alone at 5 days and 1 week post-administration. 52 …”

Fitness and therapeutic potential of intermittent hypoxia training: a matter of dose

“…None of the articles that use such concentrations describe adverse effects. There are few papers which documented adverse effects, but starting with 8-9% FiO 2 [40][41][42][43][44][45][46][47]. All study results cited in the A rightward shift in the oxyhemoglobin equilibrium response, attenuated tachycardiac response to hypoxia while significantly enhancing normoxic R-R interval variability in low-frequency and highfrequency spectra without changes in arterial blood pressure at rest or during hypoxia, i.e.…”