Respiratory dysfunction is a primary cause of morbidity and mortality following cervical spinal cord injury (cSCI). Although mechanical ventilation remains the standard of care for treating respiratory insufficiency after cSCI, chronic mechanical ventilation leads to higher incidence of comorbidities and inability to wean. Diaphragm pacing is emerging as a promising clinical alternative to chronic mechanical ventilation that mitigates many of its deleterious effects. We recently demonstrated enhanced breathing output both during and after daily pacing in rats with sub-acute cSCI1,2. In ongoing studies, we are investigating the potential to further enhance these effects (both in terms of amplitude and duration of effects) by pairing diaphragm pacing with therapeutic acute intermittent hypoxia, another promising therapeutic strategy which has been shown to enhance both respiratory plasticity and recovery after cSCI. Adult, male Sprague-Dawley rats were surgically implanted with bilateral diaphragm EMGs. One week later, rats received unilateral spinal cord hemisection at C2. Beginning 1-4 weeks after injury, rats received 4 consecutive days of diaphragm pacing with or without tAIH. Diaphragm pacing was delivered to the paralyzed hemidiaphragm (biphasic, 30Hz, 80 ms pulse width) for 1hr each day in an intermittent pattern (5 min on/5 min off). tAIH consisted of 10, 5-min episodes of hypoxia (10%O 2 ), with 5-min normoxic intervals. In rats treated with tAIH + pacing, the pacing protocol was initiated ~1 hour after the final hypoxic episode. EMG output and ventilation (recorded using whole-body plethysmography) were recorded prior to the first intervention and one day after the final intervention, as well as daily, prior to-, during-, and for 1-hr following each treatment. Preliminary analyses of plethysmography data collected during each intervention suggests that pairing tAIH with diaphragm pacing enhances ventilatory function both during and for at least one hour following treatment. Indeed, despite no differences in tidal volume prior to the start of the protocol, tidal volume was increased by more than 20% during, immediately following, and for at least one hour after pacing rats treated with tAIH prior to pacing compared to rats treated with DP alone. In ongoing studies, we are evaluating the cumulative effects of daily treatment and assessing impact of treatment on diaphragm EMG output. In separate ongoing studies, we are also evaluating the efficacy of non-surgical therapeutic approaches to drive breathing recovery (e.g. treadmill exercise) both with and without tAIH. Acknowledgements: This work was supported by funding from the Department of Defense – SC240152 (EGR/KAS) and the National Institutes of Health - R01-NS142310-01 (EGR) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Stricklin et al. (Fri,) studied this question.