Combined acute intermittent hypoxia and task specific training with hypercapnia improve breathing capacity after chronic cervical spinal cord injury

Abstract

Therapeutic acute intermittent hypoxia (tAIH) is simple, safe, and effective means of inducing respiratory motor plasticity and improving breathing in rodent models of acute cervical spinal cord injury (SCI). Unfortunately, tAIH effects on breathing function are less effective with chronic injury. On the other hand, tAIH restores non-respiratory (limb) motor function with chronic SCI, but only when combined with task specific training (TST). The efficacy of combined tAIH and respiratory TST on breathing ability in rodent models (or humans) with chronic SCI has not been investigated. Here, we explore the potential for tAIH and respiratory TST to increase breathing ability; we further differentiate automatic vs. volitional TST, since the ability to sustain independent breathing is dependent on automatic (and not volitional) breathing function, which relies on distinct neural pathways. Hypercapnia is a powerful respiratory stimulant, increasing breathing via (automatic) chemoreceptor feedback, independent of voluntary control. Thus, we explore the impact of 7 days of tAIH (10, 5-min episodes of 10.5% O2) combined with automatic, hypercapnia-induced TST (30 min, 9% inspired CO2) on breathing in unanesthetized rats with chronic (7-8 weeks) C2 spinal hemisection. In preliminary analyses, breathing capacity (i.e., ventilatory response to maximal chemoreflex activation) increased following treatment with daily AIH combined with hypercapnia (i.e., respiratory TST) in rats with chronic C2 hemisection (~17% increase). Similar improvements in breathing function were not observed with tAIH or respiratory TST alone. These are the first studies to investigate the therapeutic efficacy of combined tAIH and respiratory TST targeting automatic breathing. These initial results indicate that, similar to non-respiratory motor systems, pairing tAIH with TST improves breathing function in rodents with chronic cervical SCI. Craig H. Neilsen Foundation (SCIRP891379), NIH HL147554, and the 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 content available for this abstract. Physiology was not involved in the peer review process.