Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty

Abstract Background Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibr...

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Main Authors: Jodie L. Morris, Hayley L. Letson, Peter McEwen, Erik Biros, Constantin Dlaska, Kaushik Hazratwala, Matthew Wilkinson, Geoffrey P. Dobson
Format: Article
Language:English
Published: BMC 2021-12-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-021-02871-y
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author Jodie L. Morris
Hayley L. Letson
Peter McEwen
Erik Biros
Constantin Dlaska
Kaushik Hazratwala
Matthew Wilkinson
Geoffrey P. Dobson
author_facet Jodie L. Morris
Hayley L. Letson
Peter McEwen
Erik Biros
Constantin Dlaska
Kaushik Hazratwala
Matthew Wilkinson
Geoffrey P. Dobson
author_sort Jodie L. Morris
collection DOAJ
description Abstract Background Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery. Methods Male Sprague–Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery. Results Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1β, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68+ cells) and markers of fibrosis (α-SMA, TGF-β) were also lower in capsular tissue of ALM-treated knees at day 28. Conclusion Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.
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spelling doaj.art-ae1742be39814d9bbeb8235e83400beb2022-12-22T02:15:00ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-12-0116111510.1186/s13018-021-02871-yComparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplastyJodie L. Morris0Hayley L. Letson1Peter McEwen2Erik Biros3Constantin Dlaska4Kaushik Hazratwala5Matthew Wilkinson6Geoffrey P. Dobson7Orthopaedic Research Institute of QueenslandHeart and Trauma Research Laboratory, Division of Tropical Health and Medicine, College of Medicine and Dentistry,, James Cook UniversityOrthopaedic Research Institute of QueenslandHeart and Trauma Research Laboratory, Division of Tropical Health and Medicine, College of Medicine and Dentistry,, James Cook UniversityOrthopaedic Research Institute of QueenslandOrthopaedic Research Institute of QueenslandOrthopaedic Research Institute of QueenslandHeart and Trauma Research Laboratory, Division of Tropical Health and Medicine, College of Medicine and Dentistry,, James Cook UniversityAbstract Background Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery. Methods Male Sprague–Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery. Results Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1β, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68+ cells) and markers of fibrosis (α-SMA, TGF-β) were also lower in capsular tissue of ALM-treated knees at day 28. Conclusion Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.https://doi.org/10.1186/s13018-021-02871-yTotal knee arthroplastyStiffnessArthrofibrosisInflammationTranexamic acid
spellingShingle Jodie L. Morris
Hayley L. Letson
Peter McEwen
Erik Biros
Constantin Dlaska
Kaushik Hazratwala
Matthew Wilkinson
Geoffrey P. Dobson
Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty
Journal of Orthopaedic Surgery and Research
Total knee arthroplasty
Stiffness
Arthrofibrosis
Inflammation
Tranexamic acid
title Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty
title_full Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty
title_fullStr Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty
title_full_unstemmed Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty
title_short Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty
title_sort comparison of intra articular administration of adenosine lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty
topic Total knee arthroplasty
Stiffness
Arthrofibrosis
Inflammation
Tranexamic acid
url https://doi.org/10.1186/s13018-021-02871-y
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