Inspiratory motor activity and burst‐to‐burst variability during single and repeated bout hypoxic exposures in spontaneously breathing urethane‐anesthetized adult female rats with mid‐thoracic moderate contusion SCI

Abstract

Spinal cord injury (SCI) at either the cervical or thoracic level can lead to inefficient ventilation by disrupting descending inputs to respiratory motoneurons resulting in altered mechanics of breathing and a reduced ability to adequately and appropriately respond to ventilatory complications. Under these conditions, individuals with SCI may experience individual or repeated bouts of acute hypoxia that vary in severity and/or duration. Recently, the use of acute intermittent hypoxia (AIH) has been proposed as a potential therapeutic intervention to induce spinal motor plasticity and improve respiratory motor function following incomplete cervical (C2) SCI in both rodents and humans; however, much less is known about the effects of either single or repeated hypoxic exposures on respiratory motor output following mid‐thoracic SCI, which spares phrenic motoneurons. To begin to address this issue, we examined diaphragm EMG activity in response to 15‐min of hypoxia (12% O2) delivered as either a single 15‐min bout (protocol 1) or as three 5‐min bouts separated by 5‐min normoxic intervals (protocol 2) in spontaneously breathing urethane‐anesthetized naïve (control; n=6 protocol 1; n=8 protocol 2) or mid‐thoracic SCI (n=6 protocol 1; n=7 protocol 2) rats. Diaphragm EMG burst frequency and amplitude were measured and quantified at 15‐min intervals under baseline (BL) normoxic conditions and at 5‐min intervals during and following the hypoxic exposures. In addition, burst‐to‐burst frequency and amplitude variability were determined using coefficient of variation (CV) and Poincaré plot analyses from 300 consecutive EMG bursts. We found that in response to hypoxia, both SCI and control rats exhibited (1) increases in burst frequency and small increases or decreases in burst amplitude for both protocols, (2) increases in frequency CV values with the largest effect being noted in protocol 2 control rats during the first hypoxic exposure; (3) sustained increases in amplitude CV values for both protocols albeit a lower magnitude effect in SCI rats; (4) increases in short‐term (SD1) and long‐term (SD2) burst‐to‐burst frequency and amplitude that were attenuated in SCI rats compared to control rats, especially in protocol 1; and (5) post hypoxic frequency and amplitude decreases that were similar between the protocols. Both the ventilatory behaviors and burst‐to‐burst variability patterns observed in response to the repeated hypoxic exposures in protocol 2 appeared to be reproducible albeit in the first hypoxic exposure, SD1 and SD2 values for burst frequency tended to be higher and exhibit greater spread across control rats. These data demonstrate that while rats with mid‐thoracic contusion SCI exhibit similar single and repeated hypoxic exposure ventilatory behaviors, the respiratory dynamics of these behaviors exhibit reduced short‐term and long‐term burst‐to‐burst variability that are minimally affected by the pattern of the 15‐min duration of acute hypoxia.Support or Funding InformationDOD CDMRP W81XWH‐17‐1‐0260; NIH NS096514