Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine.
Abstract: Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. Objective: Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. Methods: Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flunixin meglumine 1 mg/kg bwt every 12 h or lidocaine 1.3 mg/kg bwt loading dose followed by 0.05 mg/kg bwt/min constant rate infusion, or both flunixin meglumine and lidocaine, with 6 horses allocated randomly to each group. Two sections of jejunum were subjected to 2 h of ischaemia by temporary occlusion of the local blood supply, via a midline celiotomy. Horses were monitored with a behavioural pain score and were subjected to euthanasia 18 h after reversal of ischaemia. Ischaemic-injured and control jejunum was mounted in Ussing chambers for measurement of transepithelial electrical resistance (TER) and permeability to lipopolysaccharide (LPS). Results: In ischaemic-injured jejunum TER was significantly higher in horses treated with saline, lidocaine or lidocaine and flunixin meglumine combined, compared to horses treated with flunixin meglumine. In ischaemic-injured jejunum LPS permeability was significantly increased in horses treated with flunixin meglumine alone. Behavioural pain scores did not increase significantly after surgery in horses treated with flunixin meglumine. Conclusions: Treatment with systemic lidocaine ameliorated the inhibitory effects of flunixin meglumine on recovery of the mucosal barrier from ischaemic injury, when the 2 treatments were combined. The mechanism of lidocaine in improving mucosal repair has not yet been elucidated.
Publication Date: 2008-03-07 PubMed ID: 18321812DOI: 10.2746/042516408X293574Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates how the use of systemic lidocaine, a common anesthetic, can help improve the recovery of mucosal tissues in horses afflicted by ischemic injury and reverse the negative effects of flunixin meglumine, a conventional pain relief medicine.
Research Context
- Ischemic injury to the intestinal jejunum mucosa is a common issue in horses undergoing colic surgery. The absorption of endotoxin (a damaging cell component of harmful bacteria) across this damaged tissue is a leading cause of death following the surgical procedure.
- A popular medication, flunixin meglumine, used for analgesia (pain relief) in such circumstances, was found to hamper the healing of the mucosa.
- Lidocaine, usually used in treating post-operative ileus (disruption of normal bowel movement), has been found to have anti-inflammatory properties that might aid the recovery of the mucosa after ischemic injury.
Aim of the Study
- The research aimed to ascertain whether lidocaine can counteract the negative effects of flunixin meglumine on mucosal healing following ischemic injury.
Methods Used
- The horses in the study were subjected to intentional ischaemia of the jejunum (interruption of the blood supply), mimicking the condition found in complicated colic surgeries. They were then treated with one of four treatments: 0.9% saline, flunixin meglumine, lidocaine, or a combination of both flunixin meglumine and lidocaine.
- Each treatment group consisted of 6 horses, assigned randomly.
- Through a series of measurements, including transepithelial electrical resistance (TER) and permeability to lipopolysaccharide (LPS), the researchers objectively evaluated the function of the mucosal barrier.
Findings
- The study found that in the ischaemic-injured jejunum, TER was significantly higher (suggesting better mucosal health) in those treated with saline, lidocaine, or a combination of both lidocaine and flunixin meglumine, compared to those given only flunixin meglumine.
- The permeability for LPS was also significantly increased in the injured jejunum of horses treated solely with flunixin meglumine, suggesting it failed to protect the mucosa from absorbing harmful endotoxins.
- Pain scores after surgery did not significantly increase for groups treated with flunixin meglumine, which suggests this drug was able to control pain effectively despite its negative effect on mucosal repair.
Conclusion
- The study concluded that lidocaine can counteract the inhibitory effects of flunixin meglumine on the recovery of the jejunum mucosal barrier following an ischemic injury.
- The exact mechanism of how lidocaine aids in mucosal repair remains undetermined and necessitates further research.
Cite This Article
APA
Cook VL, Jones Shults J, McDowell M, Campbell NB, Davis JL, Blikslager AT.
(2008).
Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine.
Equine Vet J, 40(4), 353-357.
https://doi.org/10.2746/042516408X293574 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
MeSH Terms
- Anesthetics, Local / blood
- Anesthetics, Local / therapeutic use
- Animals
- Clonixin / analogs & derivatives
- Clonixin / pharmacology
- Electric Impedance
- Female
- Horse Diseases / drug therapy
- Horse Diseases / prevention & control
- Horses
- Infusions, Intravenous / veterinary
- Intestinal Mucosa / blood supply
- Intestinal Mucosa / drug effects
- Ischemia / drug therapy
- Ischemia / prevention & control
- Ischemia / veterinary
- Jejunum / blood supply
- Jejunum / drug effects
- Jejunum / metabolism
- Lidocaine / blood
- Lidocaine / therapeutic use
- Lipopolysaccharides / pharmacology
- Male
- Pain Measurement / veterinary
- Permeability / drug effects
- Reperfusion / veterinary
- Time Factors
- Tissue Culture Techniques / veterinary
Citations
This article has been cited 14 times.- Sousa LN, Winter IC, Varela DD, Luvison EZ, Guzmán JFC, Machado AMV, Figueiredo RDV, Pena GT, Dos Santos ACS, Faleiros RR, Carvalho AM. Lidocaine's Ineffectiveness in Mitigating Lipopolysaccharide-Induced Pain and Peristaltic Effects in Horses. Animals (Basel) 2024 Nov 2;14(21).
- Wu Y, Chen Z, Yao C, Sun H, Li H, Du X, Cheng J, Wan X. Effect of systemic lidocaine on postoperative quality of recovery, the gastrointestinal function, inflammatory cytokines of lumbar spinal stenosis surgery: a randomized trial. Sci Rep 2023 Oct 17;13(1):17661.
- Grages AM, Verhaar N, Pfarrer C, Breves G, Burmester M, Neudeck S, Kästner S. Low Flow versus No Flow: Ischaemia Reperfusion Injury Following Different Experimental Models in the Equine Small Intestine. Animals (Basel) 2022 Aug 22;12(16).
- Ziegler AL, Blikslager AT. Sparing the gut: COX-2 inhibitors herald a new era for treatment of horses with surgical colic. Equine Vet Educ 2020 Nov;32(11):611-616.
- Lv X, Li X, Guo K, Li T, Yang Y, Lu W, Wang S, Liu S. Effects of Systemic Lidocaine on Postoperative Recovery Quality and Immune Function in Patients Undergoing Laparoscopic Radical Gastrectomy. Drug Des Devel Ther 2021;15:1861-1872.
- Slifer ZM, Hernandez L, Pridgen TA, Carlson AR, Messenger KM, Madan J, Krishnan BR, Laumas S, Blikslager AT. Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions. PLoS One 2021;16(4):e0250165.
- Ziegler AL, Fogle CA, Burke M, Blikslager AT. Letter to the Editor: Bias in statistics or bias in equine veterinary medicine?. Equine Vet J 2019 May;51(3):423.
- Beaussier M, Delbos A, Maurice-Szamburski A, Ecoffey C, Mercadal L. Perioperative Use of Intravenous Lidocaine. Drugs 2018 Aug;78(12):1229-1246.
- Strand-Amundsen RJ, Reims HM, Reinholt FP, Ruud TE, Yang R, Høgetveit JO, Tønnessen TI. Ischemia/reperfusion injury in porcine intestine - Viability assessment. World J Gastroenterol 2018 May 14;24(18):2009-2023.
- Blikslager A, Gonzalez L. Equine Intestinal Mucosal Pathobiology. Annu Rev Anim Biosci 2018 Feb 15;6:157-175.
- Dholakia U, Clark-Price SC, Keating SCJ, Stern AW. Anesthetic effects and body weight changes associated with ketamine-xylazine-lidocaine administered to CD-1 mice. PLoS One 2017;12(9):e0184911.
- Ziegler A, Gonzalez L, Blikslager A. Large Animal Models: The Key to Translational Discovery in Digestive Disease Research. Cell Mol Gastroenterol Hepatol 2016 Nov;2(6):716-724.
- 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.
- Davis HA, Munsterman A. Ileal impaction and jejunal enterotomy in a 4-month-old Arabian filly. Can Vet J 2012 Jan;53(1):71-4.
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