The Effects of Volatile Anesthetics on Renal Sympathetic and Phrenic Nerve Activity during Acute Intermittent Hypoxia in Rats

Abstract

Coordinated activation of sympathetic and respiratory nervous systems is crucial in responses to noxious stimuli such as intermittent hypoxia. Acute intermittent hypoxia (AIH) is a valuable model for studying obstructive sleep apnea (OSA) pathophysiology, and stimulation of breathing during AIH is known to elicit long-term changes in respiratory and sympathetic functions. The aim of this study was to record the renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA) during the AIH protocol in rats exposed to monoanesthesia with sevoflurane or isoflurane. Adult male Sprague-Dawley rats (n = 24; weight: 280-360 g) were selected and randomly divided into three groups: two experimental groups (sevoflurane group, n = 6; isoflurane group, n = 6) and a control group (urethane group, n = 12). The AIH protocol was identical in all studied groups and consisted in delivering five 3 min-long hypoxic episodes (fraction of inspired oxygen, FiO₂ = 0.09), separated by 3 min recovery intervals at FiO₂ = 0.5. Volatile anesthetics, isoflurane and sevoflurane, blunted the RSNA response to AIH in comparison to urethane anesthesia. Additionally, the PNA response to acute intermittent hypoxia was preserved, indicating that the respiratory system might be more robust than the sympathetic system response during exposure to acute intermittent hypoxia.

Keywords: acute intermittent hypoxia; isoflurane; obstructive sleep apnea; phrenic nerve activity; rats; renal sympathetic nerve activity; sevoflurane.

Figure 1

Outline of the experimental preparation and protocol in urethane (n = 12), isoflurane (n = 6) and sevoflurane (n = 6) groups. The acute intermittent hypoxia (AIH) protocol consisted in delivering five 3 min-long hypoxic episodes (fraction of inspired oxygen; FiO₂ = 0.09), separated by 3 min recovery intervals (FiO₂ = 0.5) at measured experimental time points (T0: baseline; TH1 to TH5: five hypoxic episodes; T15: 15 min following the AIH protocol). ABP: arterial blood pressure; ABS: acid–base status; Freq: ventilator frequency; MAC: minimum alveolar concentration; PNA: phrenic nerve activity; RSNA: renal sympathetic nerve activity; T_i: inspiratory time.

Figure 2

Compressed neurograms of the renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA) at baseline (T0) during five hypoxic episodes (TH1 to TH5) and at 15 min following the acute intermittent hypoxia protocol (T15) in three studied groups: (a) urethane; (b) isoflurane; (c) sevoflurane. From top to bottom: arterial blood pressure (ABP) expressed in mmHg; integrated RSNA signal (IRSNA); raw RSNA signal; integrated PNA signal (IPNA) and raw PNA signal, all expressed in arbitrary units (a.u.). Scale bar represents 20 s.

Figure 3

Fold changes in activities of (a) renal sympathetic nerve (RSNA) and (b) phrenic nerve (PNA) plotted as median and interquartile ranges at baseline (T0) during 5 hypoxic episodes (TH1 to TH5) and at 15 min following the acute intermittent hypoxia protocol (T15) in urethane, isoflurane and sevoflurane groups.

Figure 4

Fold changes in activities of (a) renal sympathetic nerve (RSNA) and (b) phrenic nerve (PNA) plotted as median and interquartile ranges during the first hypoxic episode (TH1) in urethane, isoflurane and sevoflurane groups. Dashed line represents baseline activity.

Figure 5

Changes from baseline in (a) renal sympathetic (RSNA) and (b) phrenic nerve activity (PNA) during 2nd to 5th episodes of hypoxia (TH2 to TH5) in urethane, isoflurane and sevoflurane groups. Data are expressed as changes in nerve activity per hypoxic episode and plotted as median and interquartile ranges.