Abstract
A key feature of sleep disordered breathing syndromes, such as obstructive sleep apnea is intermittent hypoxia. Intermittent hypoxia is well accepted to drive the sympathoexcitation that is frequently associated with hypertension and diabetes, with measurable effects after just 1 h. The aim of this study was to directly measure the glucose response to 1 h of acute intermittent hypoxia in pentobarbital anesthetized rats, compared to conscious rats. However, we found that while a glucose response is measurable in conscious rats exposed to intermittent hypoxia, it is suppressed in anesthetized rats. Intermittent hypoxia for 1, 2, or 8 h increased blood glucose by 0.7 ± 0.1 mmol/L in conscious rats but had no effect in anesthetized rats (−0.1 ± 0.2 mmol/L). These results were independent of the frequency of the hypoxia challenges, fasting state, vagotomy, or paralytic agents. A supraphysiological challenge of 3 min of hypoxia was able to induce a glycemic response indicating that the reflex response is not abolished under pentobarbital anesthesia. We conclude that pentobarbital anesthesia is unsuitable for investigations into glycemic response pathways in response to intermittent hypoxia in rats.
Highlights
Obstructive Sleep Apnea (OSA) (Heinzer et al, 2015; Yacoub et al, 2017) is a highly prevalent, but underdiagnosed condition characterized by repetitive airway collapse during sleep
There was a significant but biologically irrelevant effect of “priming” leading to the conclusion that pentobarbital anesthesia is incompatible with investigations of Intermittent hypoxia (IHx)-induced changes in blood glucose
A single 3min hypoxia challenge was able to evoke a significant elevation of blood glucose (2.4 ± 1.2 mmol/L; FIGURE 1 | Intermittent hypoxia (IHx) elevates blood glucose in conscious rats. (A) The Sham condition of intermittent room air delivered at the same flow rate and volume as that of intermittent hypoxia (IHx) for 1, 2, or 8 h, does not elevate blood glucose in conscious rats. 1 and 2 h of IHx significantly elevated blood glucose compared to the respective Sham conditions. (B) Individual data points for Sham and IHx treatment groups
Summary
Obstructive Sleep Apnea (OSA) (Heinzer et al, 2015; Yacoub et al, 2017) is a highly prevalent, but underdiagnosed condition characterized by repetitive airway collapse during sleep. IHx in anesthetized rodent models (Dick et al, 2007; Xing and Pilowsky, 2010; Blackburn et al, 2018; Kakall et al, 2018b; Kim et al, 2018; Roy et al, 2018; Farnham et al, 2019) and conscious humans (Louis and Punjabi, 2009; Gilmartin et al, 2010; Tamisier et al, 2011) both demonstrate persistent increases in sympathetic nerve activity. In the case of chronic IHx, conscious rodent models develop increases in blood pressure (Sharpe et al, 2013) and glucose dysregulation (Polak et al, 2013; Fu et al, 2015). We report that pentobarbital anesthesia suppresses the increase in blood glucose seen in conscious rats. There was a significant but biologically irrelevant effect of “priming” leading to the conclusion that pentobarbital anesthesia is incompatible with investigations of IHx-induced changes in blood glucose
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