Comparison of Single‐bout AIH Protocols That Differ in Timing and Number of Hypoxic Episodes on Improvement in LUT Function in Adult Rats with SCI

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). In our previous studies in rats with moderate mid‐thoracic (T8) SCI, we observed that a single bout of AIH produces sustained improvements in lower urinary tract (LUT) function characterized by decreased non‐voiding bladder contractions and increased void volume. In the present study, we extend these observations on lower LUT function in SCI rats by comparing the potential therapeutic benefits of different single‐bout AIH protocols that keep the total duration of hypoxia (15 min; 12% O2) constant but differ in timing and number of hypoxic episodes. To this end, four weeks after moderate contusion (200 kilodynes) mid‐thoracic SCI, bladder intravesical pressure was recorded in urethane‐anesthetized (1.4 g/kg), spontaneously breathing, vagally intact adult female Sprague‐Dawley rats (n = 44) during continuous infusion of saline (0.04 ml/min) into the bladder to elicit reflex micturition events. Following >60 min of baseline recording, rats were exposed to a single bout of AIH consisting of (1) three 5‐min episodes of hypoxia each separated by 5‐min exposures to room air, (2) five 3‐min episodes of hypoxia each separated by 3‐min exposures to room air, or (3) ten 1.5‐min episodes of hypoxia each separated by 1.5‐min exposures to room air. Following completion of the AIH exposure protocol, data acquisition continued for up to 120 minutes while the rats continued to breathe room air, and these data were quantified based on features measured in 30‐min bins (post‐AIH data normalized to pre‐AIH data). These analyses revealed that each of the single‐bout AIH protocols elicited long‐lasting improvements (up to 120 min post‐AIH) in LUT function. Moreover, each of the protocols appeared to be equally effective in reducing the ratio of non‐voiding/voiding bladder contractions and increasing bladder inter‐contraction interval and micturition volume. Single‐bout AIH exposure also produced transient increases in both bladder contraction threshold pressure and minimum bladder pressure. Modulation of LUT behavior during individual exposures to hypoxia and immediately following each hypoxic episode (“off effect”) were also observed, with the intensity of the “off effect” tending to be lower following short duration (e.g., 10 × 1.5‐min) hypoxic exposures. Our observations suggest that each single‐bout AIH protocol is effective in reducing non‐voiding bladder contractions and increasing micturition in SCI rats albeit subtle differences in magnitude and/or timing were noted across the protocols. These data also provide additional evidence that single‐bout AIH exposure reduces bladder overactivity and stabilizes bladder function to improve voiding efficiency in SCI rats.Support or Funding InformationDOD CDMRP W81XWH‐17‐1‐0260; NYS DOH SCIRB C32088GGThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.