Dexmedetomidine and regulation of splenic sympathetic nerve discharge

Abstract

Recent lines of inquiry indicate sedatives can influence the immune system, leading to the concept of sedative-induced immunomodulation. It has been hypothesized that sedatives may alter immune responses by modulating the sympathetic nervous system, however, little information is known regarding the effects of sedatives on regulation of splenic sympathetic nerve discharge (SND), a significant omission based on the functional role that changes in splenic SND exert on splenic cytokine gene expression. The present investigation determined the effect of systemic Dexmedetomidine (Dex) administration on the level of directly-recorded splenic SND and tested the hypothesis that the intravenous administration of Dex would inhibit splenic SND in anesthetized rats. The present results demonstrate for the first time that intravenous Dex administration significantly reduces splenic sympathetic nerve outflow in baroreceptor-intact and sinoaortic-denervated rats, indicating that Dex administration alters the central regulation of splenic SND. The present results provide new information regarding the effect of a centrally-acting alpha2-adrenergic agonist on the level of sympathetic nerve outflow to a secondary lymphoid organ that plays a critical role in peripheral immune responses.

Dexmedetomidine and regulation of splenic sympathetic nerve discharge in aged F344 rats

“…In a recent study we reported that intravenous Dex administration produced splenic and renal sympathoinhibition in young F344 rats (Kenney et al, 2014). Because sedatives are often used under medical conditions that include elderly patients, coupled with the consideration that advancing age alters SND responsiveness (see Kenney 2010), it was plausible to test the hypothesis that visceral sympathoinhibitory responses to intravenous Dex administration would be attenuated in aged compared with young F344 rats.…”

“…Anesthesia was induced by isoflurane (3–5%; Butler Animal Science) and maintained during surgical procedures using isoflurane (1.5%–2.5%), α-chloralose (80 mg/kg, ip; Sigma), and urethane (800 mg/kg, ip; Sigma) (Kenney et al, 2014). Maintenance doses of α-chloralose (35–45 mg/kg/hr) were administered intravenously and maintenance doses of urethane (200 mg/kg every 4 hours) were administered into the intraperitoneal space.…”

“…Activity was recorded biphasically with a platinum bipolar electrode after capacity-coupled preamplification (bandpass 30–3000 Hz) (Grass Instruments) from renal and splenic sympathetic nerves (Kenney et al, 2014). Filtered neurograms were full-wave rectified and integrated (time constant 10 ms) and SND was quantified as microvolts × seconds (µV·s) (Kenney et al, 2014).…”

“…Filtered neurograms were full-wave rectified and integrated (time constant 10 ms) and SND was quantified as microvolts × seconds (µV·s) (Kenney et al, 2014). SND recordings were corrected for background noise after ganglionic blockade (chlorisondamine, 5 mg/kg iv; Sigma) (Kenney et al, 2014). The adequacy of anesthesia was demonstrated by an inability of mechanical stimulation of the hindlimb or tail to increase MAP or SND.…”

“…Direct SND recordings provide an output measure of central sympathetic neural circuits and centrally-acting alpha 2 -adrenergic receptor agonists modulate SND. For example, intravenous Dexmedetomidine (Dex) administration abolishes cocaine-induced increases in skin SND in conscious humans (Menon et al, 2007; Kontak et al, 2013), reduces renal SND in anesthetized rabbits (Oku et al, 1996; Xu et al, 1998), and decreases visceral (splenic and renal) SND in young, anesthetized Fischer 344 (F344) rats (Kenney et al, 2014). …”