Acute Fluoxetine Administration Improves Intermittent Hypoxia‐induced Inspiratory Burst Amplitude Deficits During Peak LPS‐induced Neuroinflammatory Phase in Anesthetized Spontaneously Breathing Adult Male Rats

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Marcia R. Ndege ◽  
James I. Rodriguez ◽  
Irene C. Solomon
2010 ◽  
Vol 109 (2) ◽  
pp. 279-287 ◽  
Author(s):  
M. S. Sandhu ◽  
K. Z. Lee ◽  
R. F. Fregosi ◽  
D. D. Fuller

Intermittent hypoxia (IH) can induce a persistent increase in neural drive to the respiratory muscles known as long-term facilitation (LTF). LTF of phrenic inspiratory activity is often studied in anesthetized animals after phrenicotomy (PhrX), with subsequent recordings being made from the proximal stump of the phrenic nerve. However, severing afferent and efferent axons in the phrenic nerve has the potential to alter the excitability of phrenic motoneurons, which has been hypothesized to be an important determinant of phrenic LTF. Here we test the hypothesis that acute PhrX influences immediate and long-term phrenic motor responses to hypoxia. Phrenic neurograms were recorded in anesthetized, ventilated, and vagotomized adult male rats with intact phrenic nerves or bilateral PhrX. Data were obtained before (i.e., baseline), during, and after three 5-min bouts of isocapnic hypoxia. Inspiratory burst amplitude during hypoxia (%baseline) was greater in PhrX than in phrenic nerve-intact rats ( P < 0.001). Similarly, burst amplitude 55 min after IH was greater in PhrX than in phrenic nerve-intact rats (175 ± 9 vs. 126 ± 8% baseline, P < 0.001). In separate experiments, phrenic bursting was recorded before and after PhrX in the same animal. Afferent bursting that was clearly observable in phase with lung deflation was immediately abolished by PhrX. The PhrX procedure also induced a form of facilitation as inspiratory burst amplitude was increased at 30 min post-PhrX ( P = 0.01 vs. pre-PhrX). We conclude that, after PhrX, axotomy of phrenic motoneurons and, possibly, removal of phrenic afferents result in increased phrenic motoneuron excitability and enhanced LTF following IH.


2016 ◽  
Vol 121 (5) ◽  
pp. 1135-1144 ◽  
Author(s):  
Eduardo V. Lemes ◽  
Eduardo Colombari ◽  
Daniel B. Zoccal

Abdominal expiratory activity is absent at rest and is evoked during metabolic challenges, such as hypercapnia and hypoxia, or after the exposure to intermittent hypoxia (IH). The mechanisms engaged during this process are not completely understood. In this study, we hypothesized that serotonin (5-HT), acting in the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG), is able to generate active expiration. In anesthetized (urethane, ip), tracheostomized, spontaneously-breathing adult male Holtzman rats we microinjected a serotoninergic agonist and antagonist bilaterally in the RTN/pFRG and recorded diaphragm and abdominal muscle activities. We found that episodic (3 times, 5 min apart), but not single microinjections of 5-HT (1 mM) in the RTN/pFRG elicited an enduring (>30 min) increase in abdominal activity. This response was amplified in vagotomized rats and blocked by previous 5-HT receptor antagonism with ketanserin (10 µM). Episodic 5-HT microinjections in the RTN/pFRG also potentiated the inspiratory and expiratory reflex responses to hypercapnia. The antagonism of 5-HT receptors in the RTN/pFRG also prevented the long-term facilitation (>30 min) of abdominal activity in response to acute IH exposure (10 × 6–7% O for 45 s every 5 min). Our findings indicate the activation of serotoninergic mechanisms in the RTN/pFRG is sufficient to increase abdominal expiratory activity at resting conditions and required for the emergence of active expiration after IH in anesthetized animals.


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