Neuromuscular Blocking Agents' Differential Bronchoconstrictive Potential in Guinea Pig Airways

Jooste, Edmund H.; Zhang, Yi; Emala, Charles W.

doi:10.1097/01.anes.0000264763.48920.c9

Cited by 41 publications

(38 citation statements)

References 52 publications

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“…19,20 In contrast, stimulation at substantially higher voltages could induce bradycardia and bronchoconstriction. 17,18,33,34 The low-voltage VNS bronchodilation and the high-voltage VNS bradycardia with bronchoconstriction responses could be differentiated, however, by investigating the stimulation pathway rather than the applied voltages. When a ligature was placed cephalic to the electrode, thereby blocking afferent but preserving efferent nerve transmission, the bradycardia and bronchoconstriction responses were unaffected (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Feasibility of Percutaneous Vagus Nerve Stimulation for the Treatment of Acute Asthma Exacerbations

Miner

Lewis

Mosnaim

et al. 2012

Academic Emergency Medicine

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Objectives: This study assessed the feasibility of an investigational vagus nerve stimulation (VNS) device for treating acute asthma exacerbations in patients not responding to at least 1 hour of initial standard care therapy.Methods: This was a prospective, nonrandomized study of patients treated in the ED for moderate to severe acute asthma (forced expiratory volume in 1 second [FEV 1 ] 25% to 70% of predicted). Treatment entailed percutaneous placement of an electrode near the right carotid sheath and 60 minutes of VNS and continued standard care. VNS voltage was adjusted to perceived improvement, muscle twitching, or adverse events (AEs). All AEs, vital signs, FEV 1 , perceived work of breathing (WOB), and final disposition were recorded.Results: Twenty-five subjects were enrolled. There were no serious AEs and no significant changes in vital signs. No subject required terminating VNS. One patient had minor bleeding from the procedure, and one had a hematoma and withdrew prior to VNS. AEs related to VNS were temporary and included cough (1 of 24), swallowing difficulty (2 of 24), voice change (2 of 24), and muscle twitching (14 of 24). These resolved when VNS ended. The FEV 1 improved at 15 minutes (median = 15.8%, 95% confidence interval [CI] = 9.3% to 22.4%), 30 minutes (median = 21.3%, 95% CI = 8.1% to 36.5%), and 60 minutes (median = 27.5%, 95% CI = 11.3% to 43.5%). WOB improved at 15 minutes (median = 53.9%, 95% CI = 33.7% to 73.9%), 30 minutes (median = 69.1%, 95% CI = 56.4% to 81.8%), and 60 minutes (median = 81.0%, 95% CI = 68.5% to 93.5%).Conclusions: Percutaneous VNS did not result in serious AEs and was associated with improvements in FEV 1 and perceived dyspnea. Percutaneous VNS appears to be feasible for use in the treatment of moderate to severe acute asthma in patients unresponsive to initial standard care treatment.

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Section: Discussionmentioning

confidence: 99%

Feasibility of Percutaneous Vagus Nerve Stimulation for the Treatment of Acute Asthma Exacerbations

Miner

Lewis

Mosnaim

et al. 2012

Academic Emergency Medicine

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“…To characterize the role of histamine, H1 (diphenhydramine) and H2 (cimetidine) antagonists were administered to two groups of animals before the administration of atracurium, while a third group received a combination of both antagonists. In those experiments, it was evident that both receptors are involved in the hypotensive response 16,18,19 . The need of combined blockade of both receptors indicates that hypotension triggered by histamine probably has two components: an immediate reduction in blood pressure mediated by H1 receptors, and a later reduction mediated by H2 receptors 20,21 .…”

Section: Discussionmentioning

confidence: 91%

“…Histamine probably causes hypotension by affecting different areas of the same site (blood vessel). The anti-muscarinic effects of the H1 antagonist could explain the partial reversion of the reduction in blood pressure 19,23 . The effects of the histamine released on available receptors would represent another possible explanation for the partial effect observed with one of the anti-histamines.…”

Section: Discussionmentioning

confidence: 99%

Efeitos hemodinâmicos do atracúrio e do cisatracúrio e o uso de difenidramina e cimetidina

Correa¹,

Sudo²,

Sudo³

2010

Rev. Bras. Anestesiol.

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Atracurium, a benzylisoquinoline compound, is a non-depolarizing blocker of neuromuscular cholinergic receptors 5 . It is composed by a mixture of ten optical and geometrical isomers 5,6 . The incidence of atracurium-related hypotension is low, but it has been considered the etiologic factor in 18% of the episodes of anaphylaxis during anesthesia 2 . In doses higher than three times its ED 95 in humans, this drug can cause severe hypotension 5,6 . Cisatracurium, one of the 10 isomers of atracurium, has a similar profile, since evidence that isomers have a different behavior on the release of histamine does not exist 3 . The objective of the present study was to compare the hemodynamic effects of the intravenous administration of different doses of atracurium and cisatracurium in rats, and to investigate whether histamine receptor blockers, H1 (diphenhydramine) and H2 (cimetidine), protect against those hemodynamic changes. The use of diphenhydramine and cimetidine as H1 and H2 antagonists, respectively, was based on literature reports suggesting that those substances could block atracurium-induced hemodynamic actions 7,8 . METHODSAll experimental protocols used in the present study were approved by the Ethics on Animal Use Commission of the Health Sciences Center of the Universidade Federal do Rio de Janeiro (CCS-UFRJ). This study was undertaken in three steps: 1) In vivo assessment of the neuromuscular blockadeWistar Rats of both genders, weighing 300 to 450 g, were used to determine the dose necessary to promote neuromuscular blockade in rats. Animals were anesthetized with 50 mg.kg -1 of intraperitoneal sodium pentothal. The animals were intubated and the lungs were ventilated with room air with an automatic Harvard ventilator for small animals. To achieve adequate respiratory conditions, tidal volume was maintained at 10 ml.kg -1 and a respiratory rate of 50 bpm (breaths per minute). To investigate the in vivo effects of NMBs, the technique described by Brown et al. in 1936 9 was used. The sciatic nerve of one of the paws was surgically dissected and stimulated with a pair of platinum electrodes connected to a Grass S88 stimulator. The tendon of the gastrocnemius muscle was fixed to the Grass FT03 transducer with a metallic string and contractions were recorded on paper with a quill. The voltage of the stimuli and muscle stretching were adjusted to obtain maximal muscular contractions, i.e., until stimuli frequency that promoted maximal muscular contraction were achieved, which was 0.2 Hz. Thus, supramaximal stimuli were evoked to assess the neuromuscular function under the effects of the intravenous administration of atracurium or cisatracurium. Train-of-four (TOF) stimuli of 2 Hz were used to determine the occupation rate of nicotinic receptors in the muscle and to evaluate the neuromuscular function in experimental animal models, since the relationship between

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“…Male Hartley guinea pigs (ϳ400 g) were anesthetized and instrumented in this established model of airway inflation pressure measurements (5,10,14) in protocols previously described (10) and approved by the Columbia University Institutional Animal Care and Use Committee. Anesthesia was induced by intraperitoneal injection of urethane (1.5 g/kg) and increased by 0.5 g ip until lack of foot pinch response before the start of the procedure.…”

Section: Methodsmentioning

confidence: 99%

The GABA_A agonist muscimol attenuates induced airway constriction in guinea pigs in vivo

Gleason¹,

Gallos²,

Zhang³

et al. 2009

Journal of Applied Physiology

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Gleason NR, Gallos G, Zhang Y, Emala CW. The GABAA agonist muscimol attenuates induced airway constriction in guinea pigs in vivo. J Appl Physiol 106: 1257-1263, 2009. First published February 12, 2009 doi:10.1152/japplphysiol.91314.2008.-GABAA channels are ubiquitously expressed on neuronal cells and act via an inward chloride current to hyperpolarize the cell membrane of mature neurons. Expression and function of GABAA channels on airway smooth muscle cells has been demonstrated in vitro. Airway smooth muscle cell membrane hyperpolarization contributes to relaxation. We hypothesized that muscimol, a selective GABAA agonist, could act on endogenous GABAA channels expressed on airway smooth muscle to attenuate induced increases in airway pressures in anesthetized guinea pigs in vivo. In an effort to localize muscimol's effect to GABAA channels expressed on airway smooth muscle, we pretreated guinea pigs with a selective GABAA antagonist (gabazine) or eliminated lung neural control from central parasympathetic, sympathetic, and nonadrenergic, noncholinergic (NANC) nerves before muscimol treatment. Pretreatment with intravenous muscimol alone attenuated intravenous histamine-, intravenous acetylcholine-, or vagal nerve-stimulated increases in peak pulmonary inflation pressure. Pretreatment with the GABAA antagonist gabazine blocked muscimol's effect. After the elimination of neural input to airway tone by central parasympathetic nerves, peripheral sympathetic nerves, and NANC nerves, intravenous muscimol retained its ability to block intravenous acetylcholineinduced increases in peak pulmonary inflation pressures. These findings demonstrate that the GABAA agonist muscimol acting specifically via GABAA channel activation attenuates airway constriction independently of neural contributions. These findings suggest that therapeutics directed at the airway smooth muscle GABAA channel may be a novel therapy for airway constriction following airway irritation and possibly more broadly in diseases such as asthma and chronic obstructive pulmonary disease. acetylcholine; histamine; vagal nerve stimulation; gabazine; guanethidine THERE HAS BEEN A GLOBAL INCREASE in the incidence of asthma in the last 20 years (4). Current asthma treatment focuses on avoiding triggers, reducing the incidence of exacerbations, and limiting airway inflammation and chronic remodeling. There have been few new developments in the pharmacological armamentarium against asthma over the last two decades and a paucity of new developments in the treatment of acute airway smooth muscle constriction, which is essential in the treatment of acute exacerbations.Recently, our laboratory identified ␥-aminobutyric acid type A (GABA A ) channels in human and animal airway smooth muscle (12). Activation of GABA A channels in mature central nervous system neurons results in an inward chloride flux resulting in hyperpolarization of the cell membrane (2). In airway smooth muscle, plasma membrane hyperpolarization favors relaxation (11). Although in vitro studies of...

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Neuromuscular Blocking Agents' Differential Bronchoconstrictive Potential in Guinea Pig Airways

Cited by 41 publications

References 52 publications

Feasibility of Percutaneous Vagus Nerve Stimulation for the Treatment of Acute Asthma Exacerbations

Feasibility of Percutaneous Vagus Nerve Stimulation for the Treatment of Acute Asthma Exacerbations

Efeitos hemodinâmicos do atracúrio e do cisatracúrio e o uso de difenidramina e cimetidina

The GABA_A agonist muscimol attenuates induced airway constriction in guinea pigs in vivo

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