title: 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; P<0.01 vs. control) and propofol significantly prevented this effect (P>0.05 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.
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy. Electronic address: luigicalz@gmail.com.
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.affiliation: Dipartimento di Scienze Veterinarie e Sanità Pubblica (DIVET), Università degli Studi di Milano, Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Soggiu
authors.affiliation: Dipartimento di Scienze Veterinarie e Sanità Pubblica (DIVET), Università degli Studi di Milano, Milan, Italy; Istituto Sperimentale Italiano L. Spallanzani, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Roncada
authors.affiliation: Dipartimento di Scienze Veterinarie e Sanità Pubblica (DIVET), Università degli Studi di Milano, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bonizzi
authors.affiliation: CDVet, Laboratorio Analisi Veterinarie, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Pistocchini
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rinaldi
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000633:toxicity; D000771:Anesthesia, Intravenous; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006736:Horses; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D015742:Propofol / Q000008:administration & dosage*
chemical_list: D000701:Analgesics, Opioid; D015742:Propofol
keywords: Bronchial hyperresponsiveness; Drug interaction; Equine isolated bronchi; Propofol; Remifentanil; Veterinary anaesthesia