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European journal of pharmacology2015; 765; 463-471; doi: 10.1016/j.ejphar.2015.09.007

Propofol protects against opioid-induced hyperresponsiveness of airway smooth muscle in a horse model of target-controlled infusion anaesthesia.

Abstract: General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contractile response of equine isolated bronchi to electrical field stimulation (EFS) was assessed. The role of capsaicin-sensitive sensory nerves, inducible nitric oxide synthase (iNOS) and neurokinin 2 (NK2) receptor was also assessed. The interaction analysis was performed by Bliss Independence theory. Experiments were repeated in desensitized and passively sensitized airways. Remifentanil induced BHR in both non-sensitized and passively sensitized bronchi, (+56.33±8.01% and +99.10±14.52%, respectively; P0.05 vs. remifentanil). The inactivation of capsaicin-sensitive sensory nerves via desensitization and blocking NK2 receptor inhibited the BHR remifentanil-induced (P>0.05 vs. controls). The inhibition of iNOS reverted the protective effect of propofol on the BHR induced by remifentanil (non-sensitized: +47.11±7.70%; passively sensitized: +70.51±11.39%; P<0.05 vs. control). Propofol synergistically interacted (overall ≈40%) in preventing the remifentanil-induced BHR. Remifentanil induces BHR via stimulating capsaicin-sensitive sensory nerves that facilitate the cholinergic neurotransmission through the activation of NK2 receptor. The propofol/remifentanil combination may be safely administered in course of TCI-TIVA procedures also in heaves affected horses.
Publication Date: 2015-09-11 PubMed ID: 26368667DOI: 10.1016/j.ejphar.2015.09.007Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study investigates how propofol, a sedative-hypnotic drug, and remifentanil, an opioid, affect airway contraction in horses. Results suggest that remifentanil can cause hypersensitivity in the airways, which can potentially be mitigated by propofol.

Objective of the Research

  • The research was aimed to study the effect of two drugs, propofol and remifentanil, on the contractile response of horse airway smooth muscle.
  • While propofol and remifentanil are commonly used in total intravenous anaesthesia (TIVA) procedures, there was no existing data about their impact in causing bronchial hyperresponsiveness (BHR) in horses.

Methodology and Experimental Design

  • The experiment involved assessing the influence of propofol and remifentanil on equine isolated bronchi response to electrical field stimulation (EFS).
  • Factors such as the role of capsaicin-sensitive sensory nerves, inducible nitric oxide synthase (iNOS) and the neurokinin 2 (NK2) receptor were examined.
  • The interactions were analyzed using Bliss Independence theory and experiments were repeated on desensitized and passively sensitized airways.

Findings

  • The results showed that remifentanil induced BHR in both non-sensitized and passively sensitized bronchi.
  • However, the administration of propofol significantly prevented this effect, suggesting a protective role of this medication.
  • Furthermore, the inactivation of capsaicin-sensitive sensory nerves and blocking of the NK2 receptor inhibited the BHR induced by remifentanil.
  • In contrast, inhibiting iNOS, a molecule that can suppress inflammation, reverted the protective effect of propofol on BHR induced by remifentanil.
  • Overall, propofol was found to interact synergistically in preventing remifentanil-induced BHR.

Implications

  • This study suggests that remifentanil stimulates capsaicin-sensitive sensory nerves that facilitate the cholinergic neurotransmission through the activation of NK2 receptor — a pathway which leads to BHR.
  • The findings of this study indicate that the combination of propofol and remifentanil can be safely administered during TIVA procedures, even in horses affected by heaves, a chronic lung condition.

Cite This Article

APA
(2015). Propofol protects against opioid-induced hyperresponsiveness of airway smooth muscle in a horse model of target-controlled infusion anaesthesia. Eur J Pharmacol, 765, 463-471. https://doi.org/10.1016/j.ejphar.2015.09.007

Publication

ISSN: 1879-0712
NlmUniqueID: 1254354
Country: Netherlands
Language: English
Volume: 765
Pages: 463-471
PII: S0014-2999(15)30240-5

Researcher Affiliations

MeSH Terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / toxicity
  • Anesthesia, Intravenous
  • Animals
  • Bronchi / drug effects
  • Bronchi / physiopathology
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / physiology
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Horses
  • Male
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Organ Culture Techniques
  • Propofol / administration & dosage

Citations

This article has been cited 4 times.
  1. Calzetta L, Pistocchini E, Ritondo BL, Cavalli F, Camardelli F, Rogliani P. Muscarinic receptor antagonists and airway inflammation: A systematic review on pharmacological models. Heliyon 2022 Jun;8(6):e09760.
    doi: 10.1016/j.heliyon.2022.e09760pubmed: 35785239google scholar: lookup
  2. Calzetta L, Matera MG, Facciolo F, Cazzola M, Rogliani P. Beclomethasone dipropionate and formoterol fumarate synergistically interact in hyperresponsive medium bronchi and small airways. Respir Res 2018 Apr 12;19(1):65.
    doi: 10.1186/s12931-018-0770-7pubmed: 29650006google scholar: lookup
  3. Cazzola M, Calzetta L, Facciolo F, Rogliani P, Matera MG. Pharmacological investigation on the anti-oxidant and anti-inflammatory activity of N-acetylcysteine in an ex vivo model of COPD exacerbation. Respir Res 2017 Jan 24;18(1):26.
    doi: 10.1186/s12931-016-0500-ypubmed: 28118826google scholar: lookup
  4. Santus P, Signorello JC, Danzo F, Lazzaroni G, Saad M, Radovanovic D. Anti-Inflammatory and Anti-Oxidant Properties of N-Acetylcysteine: A Fresh Perspective. J Clin Med 2024 Jul 15;13(14).
    doi: 10.3390/jcm13144127pubmed: 39064168google scholar: lookup