Relaxation by sevoflurane, desflurane and halothane in the isolated guinea-pig trachea via inhibition of cholinergic neurotransmission

Abstract

We have studied relaxation of airway smooth muscle by sevoflurane, desflurane and halothane in the isolated guinea-pig trachea. Ring preparations were mounted in tissue baths filled with physiological salt solution (PSS), aerated continuously with 5% carbon dioxide in oxygen. Electrical field stimulation (EFS) elicited cholinergic contractions that were abolished by tetrodotoxin, indicating nerve-mediated responses. Anaesthetics were added to the gas aerating the tissue baths. Halothane, sevoflurane and desflurane at 0.5-1.0 MAC markedly attenuated cholinergic contractions to EFS. Initiation of contractile responses to acetylcholine (ACh) were not affected by volatile anaesthetics, suggesting prejunctional inhibition (i.e. inhibition of acetylcholine release). When added to a maintained submaximal contraction to ACh, volatile anaesthetics induced relaxation, indicating postjunctional inhibition. We conclude that sevoflurane, desflurane and halothane inhibited postganglionic cholinergic neuroeffector transmission in the trachea. The effect was probably exerted via pre- and postjunctional mechanisms (i.e. inhibition of acetylcholine release and direct muscle actions). Sevoflurane and desflurane were more potent than halothane both pre- and postjunctionally.

Relaxation of proximal and distal isolated human bronchi by halothane, isoflurane and desflurane

“…For example, in dogs in vivo, the direct relaxant effect of halothane on airway smooth muscle contributed as much as the indirect effect on the vagal pathway [4]. These direct relaxant effects in vivo have been reproduced in vitro in many animal studies [8][9][10][11][12][13][14][15][16][17][18][19]. However, the intensity of the relaxation in vitro varies widely among studies.…”

Successful Treatment of Severe Asthma Exacerbation with Sevoflurane Inhalation in the Intensive Care Unit

“…Inhalation agents also reduce airway smooth muscle tone by inhibition of acetylcholine release and by direct interference with intracellular contractile processes of ASM [5]. Hypoxia inhibits agonist-induced porcine tracheal smooth muscle contraction by a calcium independent mechanism mediated by protein kinase C and potentiates the inhibitory effect of volatile anesthetics on airway smooth muscle contraction.…”

“…Sevoflurane has a relatively high rate of metabolic degradation and is also known to produce metabolites which are potentially nephrotoxic [5,6]. Nevertheless, its prolonged use is found to be safe in various case reports, including infants and pregnant women [8][9][10][11][12].…”

Condutas no tratamento do broncoespasmo no peri-operatório

“…Halogenates directly act on the bronchial smooth muscle cell, changing intracellular calcium regulation, promoting relaxation or preventing constriction 19 . The action on pre-ganglial cholinergic receptors with acetylcholine release inhibition has recently been suggested 20 . Sympathicomimetic drugs, such as epinephrine, induce bronchodilation by non-selective b 1 and b 2 -adrenergic action.…”

“…Halogenados agem diretamente na célula muscular lisa brônquica, alterando a regulação de cálcio intracelular, promovendo relaxamento ou prevenindo constrição 19 . Ação sobre receptores colinérgicos pré-ganglionares, com inibição da liberação de acetilcolina, foi recentemente sugerida 20 . Drogas simpaticomiméticas, como epinefrina, causam broncodilatação pela ação não-seletiva adrenérgica b 1 e b 2 .…”