Naslov
Do Noradrenergic Inputs Contribute to Hypoglossal Motoneuron Activity in Decerebrate Dogs?

Autori
Radocaj, Tomislav ; Stuth, Eckehard A. ; Mustapic, Sanda ; Stucke, Astrid G. ; Zuperku, Edward J.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
American Society of Anesthesiologists (ASA) 2010 Annual Meeting

Mjesto i datum
San Diego (CA), Sjedinjene Američke Države, 16.10.2010. - 20.10.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
IHMN ; α1 receptor agonist

Sažetak
Introduction: Inspiratory hypoglossal motoneurons (IHMNs) contribute to upper airway patency during sleep and anesthesia. Noradrenergic excitatory input contributes to phasic and tonic genioglossus activity in wakefulness and non-REM sleep in freely behaving rats, while noradrenergic drive is actively suppressed in non REM sleep. We hypothetized that noradrenergic inputs to IHNNs also contribute to their activity in decerebrate dogs. We studied the effect of the adrenergic α1 receptor agonist phenylephrine (Phe), the α2 agonist Medetomidine (Med), the α1 antagonist Prazosin (Pra) and the α2 antagonist Yohimbine (Yoh) on the discharge patterns of single IHMN. Methods: The study was approved by the local Animal Care Committee and conformed to NIH standards. Dogs were vagotomized and decerebrated under isoflurane anesthesia and studied during isohypercapnic hyperoxia in the absence of anesthesia, while being mechanically ventilated. IHMNs were located in the brainstem via stereotaxic coordinates, response to picoejection of 5HT and by discharge pattern. Multibarrel micropipettes were used to record extracellular activity and picoeject agonists (Phe: 100 μM, Med: 10 μM) or antagonists (Pra: 50 μM, Yoh: 10 μM) on single IHMNs in vivo. Dose-effects were studied with increases in picoejection rate of each drug until there was no further change in activity. Drug-induced changes in discharge frequency (Fn) patterns were analyzed using cycle-triggered histograms. Data were normalized to pre-ejection controls. Statistical analysis was performed comparing control Fn to Fn during drug application. Plots of Fn patterns during drug application vs. control conditions were analyzed by linear regression. Repeated measures ANOVA and post hoc procedures were used to test for significant differences (p<0.05). Data are shown as mean and s.d. Results: Four protocols were performed. In protocol 1 we picoejected α1 and α2 agonists. Phe increased the peak inspiratory discharge frequency (Fn) to 148±39% (p=0.001) of control and the average Fn to 145±36 (n=6 p=0.003), while Med did not have any effect (n=5), showing that only α1 receptors are present on IHMNs. In protocol 2 Phe increased the peak Fn to 151±31% (n=13 p<0.012) and ave Fn to 148±27% (p=0.003). Pra did not produce any significant effect (n =13) but completely reversed the Phe effects to control level (n =13). In protocol 3 both Med (n =13) and Yoh (n=11) did not produce significant changes. In protocol 4 Pra (n=15) and Yoh (n=15) did not produce any significant changes, suggesting that there is no endogenous noradrenergic activation of IHMNs. 5HT used to identify IHMNs increased peak Fn to 249±142% (p<0.001) and ave Fn to 221±104% (p<0.001) from control. Conclusion: Picoejection of α1 agonist Phe on single IHMNs produced significant increases in Fn confirming the presence of α1 adrenergic receptors. However, neither α1 nor α2 antagonists produced any significant changes. This suggests that even though α1 receptors are present on IHMNs, there is no significant endogenous noradrenergic excitatory drive contributing to IHMN activity and that the α2 agonist Med should not directly affect IHMNs during sedation.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA