Impact of acute intermittent hypoxia (AIH) on lower urinary tract function following mid‐thoracic spinal cord contusion injury

Abstract

Exposure to acute intermittent hypoxia (AIH) has been reported to improve respiratory and non‐respiratory somatic motor function in rodents and humans, and as such has been proposed as a potential therapeutic intervention for treatment of motor incomplete spinal cord injury (SCI). The benefit of AIH exposure on lower urinary tract (LUT) function following incomplete SCI has begun to be explored by our laboratory albeit the influence of the severity of hypoxia implemented in the AIH protocol remains to be determined. Here, we investigated the potential therapeutic benefit of using 12% O2 as the hypoxic stimulus in an AIH protocol on LUT function following moderate contusion (200 kilodynes) mid‐thoracic (T8 vertebra) SCI (n=12) or sham injuries (spinal cord exposed, no injury; n=5) in adult female Sprague Dawley rats, with results from these studies being compared to our prior work using 10% O2. Four weeks following the SCI/sham, bladder intravesical pressure and external urethral sphincter (EUS) EMG activity were recorded under urethane anesthesia (1.4 g/kg) during continuous infusion of saline (0.04 ml/min) into the bladder to elicit reflex micturition events (spontaneously breathing, vagus nerves intact). Following >60 min of baseline recording, rats were exposed to a single bout of AIH consisting of three five‐minute episodes of hypoxia (12% O2) each separated by five‐minute exposures to room air. Following the AIH exposure, rats continued to spontaneously breathe room air, and data acquisition continued for up to 120 minutes. Prior to AIH, SCI rats exhibited pronounced rhythmic bladder activity consisting of both non‐voiding and voiding contractions. Typically, a series of non‐voiding bladder contractions with increasing amplitude preceded a voiding contraction, and the voiding contractions were incomplete resulting in continuous residual volume and an elevated minimum intravesical pressure. In response to each hypoxic episode, the frequency of voiding contractions increased and was associated with increased output volume and decreased minimum intravesical pressure. During the normoxic period between hypoxic episodes, there was typically a decrease in bladder contractions with increasing minimum intravesical pressure. Immediately following the end of AIH, there was a decrease in rhythmic bladder contractions and output volume that persisted for ~5–10 min, after which a more normal pattern of bladder activity (compared to baseline) emerged, characterized by predominantly a threshold‐driven pattern of bladder contraction with fewer non‐voiding contractions, increased output volume, and decreased minimum intravesical pressure. This post AIH pattern was transient, lasting for only a few cycles. Similar effects on bladder behaviors were noted using 10% O2; however, with 10% O2 the effects were more robust and longer lasting. Sham operated rats exhibited a threshold‐driven pattern of bladder activity with efficient voiding and similar hypoxia‐dependent modulation of contraction frequency and increased output volume following AIH. These data suggest that 12% O2 is effective in modulating LUT function following SCI, but additional optimization strategies are needed to improve the beneficial impact noted.Support or Funding InformationNIH NS096514; NYS DOH SCIRB C32088GGThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.