Effects of acute intermittent hypoxia on P0.1 in humans with spinal cord injury

• Published in: Physiology (Bethesda, Md.) Md.), 2023-05, Vol.38 (S1)
• Main Authors: Mir, Michela, Vose, Alicia, Brunetti, Gina, Cavka, Kathryn, DeMark, Louis, Snyder, Hannah, Wauneka, Clayton, Welch, Joseph, Nair, Jayakrishnan, Mitchell, Gordon, Fox, Emily
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2023.38.S1.5731777

Abstract only Spinal cord injury (SCI) disrupts neural pathways to respiratory motor neurons, diminishing respiratory drive and breathing function. Breathing impairment remains a leading cause of illness and death after SCI. Therapeutic acute intermittent hypoxia (tAIH; 15, 1-minute episodes of 9% inspired O 2 , 1.5 min normoxic intervals), a promising strategy to restore breathing function after SCI, promotes spinal neuroplasticity in rodent models. However, in humans, respiratory drive is unchanged after a single tAIH session; thus we tested the hypothesis that tAIH on five successive days increases neuromechanical respiratory drive in humans living with chronic SCI. Sixteen participants with chronic SCI (1 female; 33.5 + 15.3 years of age; 1-28 years post-SCI; 11 cervical, 5 thoracic; C1-T6 AIS A-D) were studied; their respiratory function was 52% ± 19% of age predicted expiratory pressure generation, and 123% ± 32% for inspiratory pressure. Five days of tAIH or Sham treatment were delivered in a randomized, cross-over design (minimum 3 weeks apart). Airway occlusion pressure in the first 0.1s of inspiration (P0.1), a surrogate for neuromechanical respiratory drive prior to within-breath sensory feedback, was collected at baseline and at 1, 3, and 7-days post-treatment. Repeated measures ANOVA revealed no significant effect of time (F(3)=.49; P=.69) or group (F(3)=1.33; P=.27). Despite the lack of significant differences in this preliminary analysis, P0.1 increased by 25% on day 3 versus 0.8% after Sham. Because of this change, pairwise comparisons were conducted, revealing a near significant increase in P0.1, 3 days post tAIH (MD=-.17; P =.06). Thus, although P0.1, a surrogate for neuromechanical respiratory drive, did not significantly increase after 5 days of AIH in people with SCI, the marginally significant change at day 3 suggests further investigation is warranted. Next steps include assessment in a larger sample, investigation of biomarkers for treatment effects, and examination of combinatorial interventions including task specific training and/or mild CO 2 elevations to enhance AIH-induced neuroplasticity in the drive to breathe. DoD SCIRP Clinical Trial Award W81XWH-17-SCIRP-CTA; The Craig H. Neilsen Foundation (JW); NIH T32 HL134621 (MM); and the UF McKnight Brain Institute. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional c