Ethanol pre-exposure attenuates the hypoxic ventilatory response and may attenuate expression of long term facilitation following intermittent hypoxia treatment in adult rats
Authors: Silverstein Aaron , Alilain Warren 
Published: May 2024

Obstructive sleep apnea (OSA) is a highly prevalent breathing disorder in which airway collapse or obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures during sleep can induce intermittent hypoxemia, sympathetic activation, and sleep fragmentation which can lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia, which consists of alternating exposure to hypoxia and normal oxygen levels (normoxia), can induce a long-lasting increase in breathing motor output called long term facilitation (LTF) and is currently being investigated as a therapeutic treatment. Interestingly, experts in the field of LTF have noted how IH models some key aspects of OSA. It has been well established through clinical studies that ethanol consumption prior to sleep exacerbates existing OSA, increasing the apnea/hypopnea index and worsening arterial blood oxygen desaturations during the night. However, it is unknown whether ethanol affects expression of LTF following IH treatment. If LTF might serve as a means of increasing ventilatory output to compensate for periods of apnea and hypopnea during OSA, ethanol might not only worsen the severity of OSA, but impede individuals’ compensatory response. Thus, for this study we hypothesized that ethanol treatment would attenuate LTF expression and the magnitude of the hypoxic ventilatory response during IH treatment. Using adult female Sprague-Dawley rats, we administered either low-dose (0.8 g/kg) or high-dose (3 g/kg) ethanol through intraperitoneal injection to model a 2-drink nightcap or binge drinking-type ethanol exposure, respectively. Immediately afterwards, we measured subjects’ ventilatory output during baseline, then during a 5 by 3-minute moderate IH protocol, and for one hour following the end of IH using whole-body plethysmography. Finally, we took venous blood samples to assay serum ethanol concentration at the end of the approximately 2.5 hour plethysmography measurement. Results from the high-dose ethanol group indicate that ethanol pre-exposure might attenuate respiratory rate and minute volume LTF in comparison to saline-treated control. Furthermore, high-dose ethanol attenuated the hypoxic ventilatory response with respect to respiratory rate and minute volume. Low dosage of ethanol attenuated subjects’ HVR of respiratory rate and minute volume, but conflictingly trends towards increasing LTF of tidal volume while diminishing LTF of respiratory rate when compared to saline control. Overall, our findings indicate that high levels of ethanol exposure dramatically diminish the acute ventilatory response to hypoxic exposure and may impede long-term increases in ventilatory output following IH treatment. On the other hand, lower doses of ethanol have a subtler effect on the ventilatory response to hypoxia. Future directions will include analysis of additional parameters of ventilatory function to gain a more detailed understanding of how ethanol effects respiratory plasticity in the context of intermittent hypoxic exposure.

NIH 5T32 AA027488 to ALSUniversity of Kentucky Endowment to WJA.

This is the full abstract presented at the American Physiology Summit 2024 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.