Effects of neuromuscular blocking agents on central respiratory control in the isolated brainstem–spinal cord of neonatal rat

Shibata, Shigeki; Kuwana, Shun-ichi; Ochiai, Ryoichi; Okada, Yasumasa; Kashiwagi, Masanori; Hatori, Eiki; Takeda, Junzo

doi:10.1016/s0168-0102(03)00213-x

Cited by 8 publications

(12 citation statements)

References 39 publications

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“…In our previous study (Sakuraba et al, 2003), neuromuscular blocking agents themselves have inhibitory effects on respiratory activity in the isolated brainstem spinal cord of neonatal rats that have no blood brain barrier. However, neuromuscular blocking agents can hardly pass blood brain barrier (Fahey et al, 1990;Werba et al, 1992;Fuchs Buder et al, 2004) and thus can be thought not to affect respiratory activity.…”

Section: Methodsmentioning

confidence: 88%

“…Among these candidates, only physostigmine, an acetylcholinesterase inhibitor, is clinically used and can antagonize opiate-induced respiratory depression (Weinstock et al, 1980;Weinstock et al, 1981;Willette et al, 1986;Snir-Mor et al 1983;Berkenbosch et al, 1994). Acetylcholine (ACh) is an excitatory neurotransmitter in central respiratory control (Murakoshi et al, 1985;Monteau et al, 1990;Burton et al 1995;Shao and Feldman, 2000, 2001, 2002Sakuraba et al 2003), including central chemosensitivity (Monteau et al, 1990;Burton et al 1997;Eugenin and Nicholls, 1997;Eugenin et al, 2001;Okada et al, 2001;Sakuraba et al 2005) and opiates can inhibit the release of ACh from neurons in the central nervous system (Jhamandas et al, 1971;Domino and Wilson, 1973;Zsilla et al, 1977). However, physostigmine has numerous disadvantages, e.g.…”

Section: Introductionmentioning

confidence: 99%

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Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

et al. 2007

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Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease) can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal CO 2 . In the other experiment, apneic threshold PaCO 2 was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit.

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Section: Methodsmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

et al. 2007

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“…We used a separate perfusion system 16,19,22,23 to permit selective medullary or spinal application of drugs. The chamber was partitioned at the spinomedullary junction to permit the selective application of drugs.…”

Section: Experiments 2: Separate Perfusion Of Sevoflurane To the Spinamentioning

confidence: 99%

Neural Mechanisms of Sevoflurane-induced Respiratory Depression in Newborn Rats

Kuribayashi

Shibata²,

Kashiwagi

et al. 2008

Anesthesiology

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Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Bötzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Bötzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. gamma-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.

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“…The isolated brainstem-spinal cord has been described in detail elsewhere (Kuwana et al, 1998;Sakuraba et al, 2003). In brief, the rats were deeply anesthetized with diethyl ether, and the brainstem and cervical spinal cord were isolated in a chamber filled with oxygenated artificial cerebrospinal fluid (ACSF).…”

Section: Isolated Brainstem-spinal Cord Preparationmentioning

confidence: 99%

“…Recent studies have indicated that both Pre-I neurons and Insp neurons are essential for respiratory rhythmogensis in brainstemspinal cord preparations (Takeda et al, 2001;Mellen et al, 2003;Sakuraba et al, 2003). In a previous study, we found that neuromuscular blocking agents (NMBAs), which function as muscular nAChR antagonists, exert their inhibitory effects on Pre-I neurons (Sakuraba et al, 2003). This finding led us to hypothesize that some subtypes of nAChRs might participate in the modulation of respiratory activities, such as rhythm generation, in the central respiratory network, comprising both Pre-I and Insp neurons.…”

Section: Introductionmentioning

confidence: 99%

Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats

et al. 2006

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Nicotine exposure is a risk factor in several breathing disorders Nicotinic acetylcholine receptors (nAChRs) exist in the ventrolateral medulla, an important site for respiratory control. We examined the effects of nicotinic acetylcholine neurotransmission on central respiratory control by addition of a nAChR agonist or one of various antagonists into superfusion medium in the isolated brainstem-spinal cord from neonatal rats. Ventral C4 neuronal activity was monitored as central respiratory output, and activities of respiratory neurons in the ventrolateral medulla were recorded in whole-cell configuration. RJR-2403 (0.1-10µM), α4β2 nAChR agonist induced dose-dependent increases in respiratory frequency. Non-selective nAChR antagonist mecamylamine (0.1-100µM), α4β2 antagonist dihydro-β-erythroidine (0.1-100µM), α7 antagonist methyllycaconitine (0.1-100µM), and α-bungarotoxin (0.01-10µM) all induced dose-dependent reductions in C4 respiratory rate. We next examined effects of 20µM dihydro-β-erythroidine and 20µM methyllycaconitine on respiratory neurons. Dihydro-β-erythroidine induces hyperpolarization and decreases intraburst firing frequency of inspiratory and preinspiratory neurons. In contrast, methyllycaconitine has no effect on the membrane potential of inspiratory neurons, but does decrease their intraburst firing frequency while inducing hyperpolarization and decreasing intraburst firing frequency in preinspiratory neurons. These findings indicate that α4β2 nAChR is involved in both inspiratory and preinspiratory neurons, whereas α7 nAChR functions only in preinspiratory neurons to modulate C4 respiratory rate.

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Effects of neuromuscular blocking agents on central respiratory control in the isolated brainstem–spinal cord of neonatal rat

Cited by 8 publications

References 39 publications

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

Neural Mechanisms of Sevoflurane-induced Respiratory Depression in Newborn Rats

Association of nicotinic acetylcholine receptors with central respiratory control in isolated brainstem-spinal cord preparation of neonatal rats

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