Lidocaine and structure-related mexiletine induce similar contractility-enhancing effects in ischaemia-reperfusion injured equine intestinal smooth muscle in vitro.
Abstract: Postoperative ileus (POI) is a severe complication following small intestinal surgery in horses. It was hypothesised that prokinetic effects of lidocaine, the most commonly chosen drug for treatment of POI, resulted from drug integration into smooth muscle (SM) cell membranes, thereby modulating cell membrane properties. This would probably depend on the structural and lipophilic characteristics of lidocaine. To assess the influence of molecular structure and lipophilicity on prokinetic effects in vitro, the current study compared the effects of lidocaine with four structure-related drugs, namely, mexiletine, bupivacaine, tetracaine and procaine. The response to cumulative drug administration and reversibility of effects were tested by measuring isometric contractile performance of equine jejunal circular SM strips, challenged by a standardised, artificial in vivo ischaemia-reperfusion injury. A second set of SM strips were incubated with the different drugs to determine changes in creatine kinase (CK) release. All drugs caused a drug-specific increase in contractility, although only lidocaine and mexiletine induced similar concentration-dependent curve progressions, significantly reduced CK release, and featured shorter recovery times of tissue contractility after washing, compared to bupivacaine and tetracaine. In was concluded that the structural and lipophilic similarity of mexiletine and lidocaine were responsible for the similar effects of these drugs on SM contractility and cell membrane permeability, which supported the hypothesis that prokinetic effects of lidocaine are based on interactions with SM cell membranes modulated by these features.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication Date: 2012-12-20 PubMed ID: 23265867DOI: 10.1016/j.tvjl.2012.11.011Google Scholar: Lookup
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- Journal Article
Summary
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The research hypothesizes that lidocaine drugs impact the functioning of smooth muscle cell membranes to treat Postoperative ileus (POI), a significant complication in horses after small intestinal surgery. The study focuses particularly on understanding the influence of the molecular structure and lipophilicity, examining lidocaine’s effects and four other structurally-related drugs – mexiletine, bupivacaine, tetracaine, and procaine.
Examination of Prokinetic Effects
- The study designed an in vitro model to assess the effects of the structural resemblance and lipophilicity on these drugs’ prokinetic effects. Isometric contractile performance of equine jejunal circular muscle strips was measured after being subjected to artificial, standardized in vivo ischaemia-reperfusion injury.
- The muscle strips were treated with cumulative doses of these drugs and studied for reversibility effects.
- In parallel, another set of muscle strips was incubated with these drugs to check for changes in creatine kinase (CK) release, a key player in cellular energy metabolism.
Effect of Drugs on Smooth Muscle Contractility
- All drugs being tested led to different levels of increase in muscle contractility.
- Lidocaine and the structurally-related drug, mexiletine, showed similar concentration-dependent curve progressions. Compared to bupivacaine and tetracaine, they not only significantly reduced CK release but also showed quicker recovery of tissue contractility upon washing.
Conclusion
- The shared structural and lipophilic properties of lidocaine and mexiletine were found to be responsible for their similar impacts on the contractility of smooth muscle and cell membrane permeability.
- This study thus supports the initial hypothesis that the prokinetic effects of lidocaine are due to its interaction and modification of smooth muscle cell membranes, influenced by its structural and lipophilic characteristics.
Cite This Article
APA
Tappenbeck K, Hoppe S, Hopster K, Kietzmann M, Feige K, Huber K.
(2012).
Lidocaine and structure-related mexiletine induce similar contractility-enhancing effects in ischaemia-reperfusion injured equine intestinal smooth muscle in vitro.
Vet J, 196(3), 461-466.
https://doi.org/10.1016/j.tvjl.2012.11.011 Publication
Researcher Affiliations
- Department of Physiology, University of Veterinary Medicine, Bischofsholer Damm 15, D-30173 Hannover, Germany.
MeSH Terms
- Animals
- Creatine Kinase / metabolism
- Horses
- Intestines / blood supply
- Intestines / pathology
- Lidocaine / pharmacology
- Male
- Mexiletine / pharmacology
- Muscle Contraction / drug effects
- Muscle, Smooth / drug effects
- Muscle, Smooth / enzymology
- Muscle, Smooth / pathology
- Reperfusion Injury
- Voltage-Gated Sodium Channel Blockers / pharmacology
Citations
This article has been cited 3 times.- Verhaar N, Hoppe S, Grages AM, Hansen K, Neudeck S, Kästner S, Mazzuoli-Weber G. Dexmedetomidine Has Differential Effects on the Contractility of Equine Jejunal Smooth Muscle Layers In Vitro.. Animals (Basel) 2023 Mar 10;13(6).
- Röhm K, Diener M, Huber K, Seifert J. Characterization of Cecal Smooth Muscle Contraction in Laying Hens.. Vet Sci 2021 May 26;8(6).
- Salem SE, Proudman CJ, Archer DC. Has intravenous lidocaine improved the outcome in horses following surgical management of small intestinal lesions in a UK hospital population?. BMC Vet Res 2016 Jul 27;12(1):157.
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