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Veterinary surgery : VS2024; doi: 10.1111/vsu.14186

Intrathecal enalapril reduces adhesion formation in experimentally induced digital flexor tendon sheath injuries in horses.

Abstract: The objectives of the study were to describe a standing percutaneous adhesion induction model in the digital flexor tendon sheath (DFTS) of horses and to evaluate the effect of intrathecal administration of the angiotensin-converting enzyme (ACE) inhibitor enalapril on tendon healing and adhesion formation. Methods: Randomized, blinded, controlled experimental study. Methods: Eight healthy horses. Methods: A collagenase-induced adhesion model was implemented in the deep digital flexor tendon (DDFT) of both forelimbs under standing ultrasonographic guidance. Daily intrathecal injections of 5 mg enalapril (the treatment condition) were administered to a randomly assigned forelimb for 5 days, with the contralateral limb receiving an equivalent volume of 0.9% NaCl (the control). Lameness and limb circumference were recorded weekly. Horses were euthanized after 8 weeks and evaluated for gross digital flexor tendon sheath (DFTS) adhesions. Tendons were collected for histopathologic scoring of DDFT healing. Paired data were analyzed using a one-sided alternative sign test and longitudinal regression. Results: Multiple DFTS adhesions were formed in control limbs of all horses. The median number of gross DFTS adhesions in treated limbs was less than in control limbs (p = .0039). The average reduction in limb circumference and lameness scores over time occurred faster in treated versus control limbs (p < .025). There were no differences in DDFT histopathologic scores between groups. Conclusions: The standing percutaneous DFTS adhesion induction model demonstrated that intrathecal enalapril reduced DFTS adhesion formation, lameness scores, and limb circumference over time. Conclusions: Intrathecal enalapril administration may reduce morbidity in horses with naturally occurring tendon injuries.
Publication Date: 2024-11-05 PubMed ID: 39498787DOI: 10.1111/vsu.14186Google Scholar: Lookup
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  • Journal Article

Summary

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This study investigated the effect of injecting enalapril, an angiotensin-converting enzyme (ACE) inhibitor, into the sheaths of tendon injuries in horses. The findings suggest that this treatment can reduce complications such as adhesion formation and associated swelling and limping in horse tendon injuries.

Objectives and Methods

  • The prime aim of the study was to illustrate a model for generating adhesions (scar tissue) in the digital flexor tendon sheath (DFTS) of horses when they’re standing and to assess the impact of intrathecal (administered into the space around the spinal cord) enalapril in the healing process.
  • A randomized, controlled, and blinded experimental design was applied, involving eight healthy horses.
  • The researchers induced a model of adhesions in the deep digital flexor tendon (DDFT) in both front legs of the horses using ultrasonographic guidance.
  • The horses received either the treatment (daily intrathecal injections of 5 mg enalapril) or control (an equivalent volume of 0.9% NaCl solution) for 5 days. The assignment of the forelimb to receive the treatment was selected randomly.
  • The team regularly recorded any signs of lameness and changes in limb circumference weekly. At the end of 8 weeks, all horses were euthanized, and their tendons were evaluated for any potential DFTS adhesions. The study also evaluated the healing of the DDFT using histopathology.

Results

  • The study found that all horses receiving the control treatment developed multiple adhesions in their tendons.
  • Horses receiving the enalapril treatment demonstrated significantly fewer DFTS adhesions, decreased limb circumference, and reduced lameness scores compared to control horses.
  • Despite the noted differences in adhesions, lameness, and limb circumference, the histopathology scores indicated no significant difference in tendon healing between the treatment and control groups.

Conclusion

  • This study’s findings support that using intrathecal enalapril can reduce adhesion formation in the DFTS. It also appears to have additional benefits, including a reduction in lameness scores and limb circumference over time.
  • While it did not significantly impact the histopathological healing scores, the reduction in tendon adhesions might make enalapril a worthy intervention to consider for naturally occurring tendon injuries in horses.

Cite This Article

APA
Willette JA, Tsoi M, Frobish D, VanderBroek AR. (2024). Intrathecal enalapril reduces adhesion formation in experimentally induced digital flexor tendon sheath injuries in horses. Vet Surg. https://doi.org/10.1111/vsu.14186

Publication

ISSN: 1532-950X
NlmUniqueID: 8113214
Country: United States
Language: English

Researcher Affiliations

Willette, Jaclyn A
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Tsoi, Mayra
  • Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, Lansing, Michigan, USA.
Frobish, Daniel
  • Department of Statistics, College of Liberal Arts and Sciences, Grand Valley State University, Allendale, Michigan, USA.
VanderBroek, Ashley R
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.

Grant Funding

  • RH082218-VANDE / Robert & Janet Hafner Fund for Animal Health fund via the Endowed Research Funds

References

This article includes 53 references
  1. Amadio PC. Friction of the gliding surface. Implications for tendon surgery and rehabilitation.. J Hand Ther 2005;18(2):112‐119.
    doi: 10.1197/j.jht.2005.02.005google scholar: lookup
  2. Capella-Monsonís H, Kearns S, Kelly J. Battling adhesions: from understanding to prevention.. BMC Biomed Eng 2019;1:5.
    doi: 10.1186/s42490-019-0005-0google scholar: lookup
  3. Tang JB. Clinical outcomes associated with flexor tendon repair.. Hand Clin 2005;21(2):199‐210.
    doi: 10.1016/j.hcl.2004.11.005google scholar: lookup
  4. Voleti PB, Buckley MR, Soslowsky LJ. Tendon healing: repair and regeneration.. Annu Rev Biomed Eng 2012;14:47‐71.
  5. Gaughan EM, Nixon AJ, Krook LP. Effects of sodium hyaluronate on tendon healing and adhesion formation in horses.. Am J Vet Res 1991;52(5):764‐773.
  6. Dyson SJ, Denoix JM. Tendon, tendon sheath, and ligament injuries in the pastern.. Vet Clin North Am Equine Pract 1995;11(2):217‐233.
  7. Dik KJ, Dyson SJ, Vail TB. Aseptic tenosynovitis of the digital flexor tendon sheath, fetlock and pastern annular ligament constriction.. Vet Clin North Am Equine Pract 1995;11(2):151‐162.
  8. Meier Bürgisser G, Buschmann J. History and performance of implant materials applied as peritendinous antiadhesives.. J Biomed Mater Res B Appl Biomater 2015;103(1):212‐228.
    doi: 10.1002/jbm.b.33182google scholar: lookup
  9. Meier Bürgisser G, Calcagni M, Bachmann E. Rabbit Achilles tendon full transection model ‐ wound healing, adhesion formation and biomechanics at 3, 6 and 12 weeks post‐surgery.. Biol Open 2016;5(9):1324‐1333.
    doi: 10.1242/bio.020644google scholar: lookup
  10. Taylor SH, Al-Youha S, Van Agtmael T. Tendon is covered by a basement membrane epithelium that is required for cell retention and the prevention of adhesion formation.. PLoS One 2011;6(1):e16337.
  11. Kajikawa Y, Morihara T, Watanabe N. GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing.. J Cell Physiol 2007;210(3):684‐691.
    doi: 10.1002/jcp.20876google scholar: lookup
  12. Tomlinson JE, Byrne E, Pusterla N. The use of recombinant tissue plasminogen activator (rTPA) in the treatment of fibrinous pleuropneumonia in horses: 25 cases (2007–2012).. J Vet Intern Med 2015;29(5):1403‐1409.
    doi: 10.1111/jvim.13594google scholar: lookup
  13. Bäumer W, Herrling GM, Feige K. Pharmacokinetics and thrombolytic effects of the recombinant tissue‐type plasminogen activator in horses.. BMC Vet Res 2013;9(9):158.
    doi: 10.1186/1746-6148-9-158google scholar: lookup
  14. Bulbuller N, Ilhan YS, Kirkil C. Can angiotensin converting enzyme inhibitors prevent postoperative adhesions?. J Surg Res 2005;125(1):94‐97.
    doi: 10.1016/j.jss.2004.11.030google scholar: lookup
  15. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis.. N Engl J Med 1994;331(19):1286‐1292.
  16. Biernacka A, Dobaczewski M, Frangogiannis NG. TGF‐β signaling in fibrosis.. Growth Factors 2011;29(5):196‐202.
  17. Roberts AB. Transforming growth factor‐beta: activity and efficacy in animal models of wound healing.. Wound Repair Regen 1995;3(4):408‐418.
  18. Shi Y, Massagué J. Mechanisms of TGF‐beta signaling from cell membrane to the nucleus.. Cell 2003;113(6):685‐700.
  19. Wolf G, Haberstroh U, Neilson EG. Angiotensin II stimulates the proliferation and biosynthesis of type I collagen in cultured murine mesangial cells.. Am J Pathol 1992;140(1):95‐107.
  20. Fang QQ, Wang XF, Zhao WY. Angiotensin‐converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF‐β1 pathways.. Sci Rep 2018;8(1):3332.
  21. Yasak T, Özkaya Ö, Ergan Şahin A, Aksu Sayman Ö, Bozdağ E. The efficacy of angiotensin‐converting enzyme inhibitors in preventing postoperative tendon adhesion formation: an experimental study in rats.. Acta Orthop Traumatol Turc 2022;56(1):1‐7.
    doi: 10.5152/j.aott.2022.21231google scholar: lookup
  22. ANON. Guide to Veterinary Services for Horse Shows.. 7th ed. American Association of Equine Practitioners; 1999.
  23. Edinger J, Möbius G, Ferguson J. Comparison of tenoscopic and ultrasonographic methods of examination of the digital flexor tendon sheath in horses.. Vet Comp Orthop Traumatol 2005;18(4):209‐214.
  24. Padaliya NR, Ranpariya JJ, Kumar D, Javia CB, Barvalia DR. Ultrasonographic assessment of the equine palmar tendons.. Vet World 2015;8(2):208‐212.
  25. Crovace A, Lacitignola L, Rossi G, Francioso E. Histological and immunohistochemical evaluation of autologous cultured bone marrow mesenchymal stem cells and bone marrow mononucleated cells in collagenase‐induced tendinitis of equine superficial digital flexor tendon.. Vet Med Int 2010;2010:250978.
    doi: 10.4061/2010/250978google scholar: lookup
  26. Auer JA, Stick JA, Kümmerle JM, Prange T. Phalanges and the metacarpophalangeal and metatarsophalangeal joints.. Equine Surgery. 5th ed. Elsevier; 2019:1612.
  27. Dykgraaf S, Dechant JE, Johns JL, Christopher MM, Bolt DM, Snyder JR. Effect of intrathecal amikacin administration and repeated centesis on digital flexor tendon sheath synovial fluid in horses.. Vet Surg 2007;36(1):57‐63.
  28. Bussières G, Jacques C, Lainay O. Development of a composite orthopaedic pain scale in horses.. Res Vet Sci 2008;85(2):294‐306.
  29. Jacobson E, Dart AJ, Mondori T. Focal experimental injury leads to widespread gene expression and histologic changes in equine flexor tendons.. PLoS One 2015;10(4):e0122220.
  30. Smith RKW. Tendon and Ligament Injury.. American Association of Equine Practitioners 60th Annual Convention Proceedings; 2008:54.
  31. Bates SJ, Morrow E, Zhang AY, Pham H, Longaker MT, Chang J. Mannose‐6‐phosphate, an inhibitor of transforming growth factor‐beta, improves range of motion after flexor tendon repair.. J Bone Joint Surg Am 2006;88(11):2465‐2472.
    doi: 10.2106/jbjs.e.00143google scholar: lookup
  32. Branford OA, Klass BR, Grobbelaar AO, Rolfe KJ. The growth factors involved in flexor tendon repair and adhesion formation.. J Hand Surg Eur 2014;39(1):60‐70.
    doi: 10.1177/1753193413509231google scholar: lookup
  33. Chang J, Thunder R, Most D, Longaker MT, Lineaweaver WC. Studies in flexor tendon wound healing: neutralizing antibody to TGF‐beta1 increases postoperative range of motion.. Plast Reconstr Surg 2000;105(1):148‐155.
  34. Chen CH, Zhou YL, Wu YF, Cao Y, Gao JS, Tang JB. Effectiveness of microRNA in Down‐regulation of TGF‐beta gene expression in digital flexor tendons of chickens: in vitro and in vivo study.. J Hand Surg Am 2009;34(10):1777‐1784.e1.
  35. Sener M, Akhan S, Kazimoglu C, Karapinar H, Tuna B, Cecen B. The effects of suramin in prevention of peritendinous adhesions following flexor tendon injury in a chicken model.. Orthopedics 2008;31(6):542.
  36. Krause DM, Pezzanite LM, Griffenhagen GM, Hendrickson DA. Comparison of equine synovial sepsis rate following intrasynovial injection in ambulatory versus hospital settings.. Equine Vet J 2022;54(3):523‐530.
    doi: 10.1111/evj.13485google scholar: lookup
  37. Pezzanite L, Chow L, Soontararak S, Phillips J, Goodrich L, Dow S. Amikacin induces rapid dose‐dependent apoptotic cell death in equine chondrocytes and synovial cells in vitro.. Equine Vet J 2020;52(5):715‐724.
    doi: 10.1111/evj.13243google scholar: lookup
  38. Pezzanite L, Chow L, Piquini G. Use of in vitro assays to identify antibiotics that are cytotoxic to normal equine chondrocytes and synovial cells.. Equine Vet J 2021;53(3):579‐589.
    doi: 10.1111/evj.13314google scholar: lookup
  39. Pezzanite L, Chow L, Hendrickson D. Evaluation of intra‐articular amikacin Administration in an Equine non‐inflammatory Joint Model to identify effective bactericidal concentrations while minimizing cytotoxicity.. Front Vet Sci 2021;8:676774.
    doi: 10.3389/fvets.2021.676774google scholar: lookup
  40. Gómez-Díez M, Muñoz A, Caballero JMS, Riber C, Castejón F, Serrano-Rodríguez JM. Pharmacokinetics and pharmacodynamics of enalapril and its active metabolite, enalaprilat, at four different doses in healthy horses.. Res Vet Sci 2014;97(1):105‐110.
  41. Sleeper MM, McDonnell SM, Ely JJ, Reef VB. Chronic oral therapy with enalapril in normal ponies.. J Vet Cardiol 2008;10(2):111‐115.
    doi: 10.1016/j.jvc.2008.08.002google scholar: lookup
  42. Malark JA, Nixon AJ, Skinner KL, Mohammed H. Characteristics of digital flexor tendon sheath fluid from clinically normal horses.. Am J Vet Res 1991;52(8):1292‐1294.
  43. Foland JW, Trotter GW, Powers BE, Wrigley RH, Smith FW. Effect of sodium hyaluronate in collagenase‐induced superficial digital flexor tendinitis in horses.. Am J Vet Res 1992;53(12):2371‐2376.
  44. Wu YF, Tang JB. Apoptosis in adhesions and the adhesion‐tendon gliding interface: relationship to adhesion‐tendon gliding mechanics.. J Hand Surg Am 2013;38(6):1071‐1078.
  45. Wu YF, Tang JB. Tendon healing, edema, and resistance to flexor tendon gliding: clinical implications.. Hand Clin 2013;29(2):167‐178.
    doi: 10.1016/j.hcl.2013.02.002google scholar: lookup
  46. Jørgensen HG, McLellan SD, Crossan JF, Curtis AS. Neutralisation of TGF beta or binding of VLA‐4 to fibronectin prevents rat tendon adhesion following transection.. Cytokine 2005;30(4):195‐202.
  47. Katzel EB, Wolenski M, Loiselle AE. Impact of Smad3 loss of function on scarring and adhesion formation during tendon healing.. J Orthop Res 2011;29(5):684‐693.
    doi: 10.1002/jor.21235google scholar: lookup
  48. Spaas JH, Guest DJ, Van de Walle GR. Tendon regeneration in human and equine athletes: Ubi Sumus‐quo Vadimus (where are we and where are we going to)?. Sports Med 2012;42(10):871‐890.
    doi: 10.1007/bf03262300google scholar: lookup
  49. Crosby DE, Labens R, Hughes KJ, Nielsen S, Hilbert BJ. Factors associated with survival and return to function following synovial infections in horses.. Front Vet Sci 2019;6:367.
    doi: 10.3389/fvets.2019.00367google scholar: lookup
  50. Wereszka MM, White NA, Furr MO. Factors associated with outcome following treatment of horses with septic tenosynovitis: 51 cases (1986–2003).. J Am Vet Med Assoc 2007;230(8):1195‐1200.
    doi: 10.2460/javma.230.8.1195google scholar: lookup
  51. Arensburg L, Wilderjans H, Simon O, Dewulf J, Boussauw B. Nonseptic tenosynovitis of the digital flexor tendon sheath caused by longitudinal tears in the digital flexor tendons: a retrospective study of 135 tenoscopic procedures: tenosynovitis caused by longitudinal tears in the digital flexor tendons.. Equine Vet J 2011;43(6):660‐668.
  52. McIlwraith CW. Diseases of joints, tendons, ligaments and related structures.. In: Stashak TS, ed. Adam's Lameness in Horses. Lea & Febiger; 1987:612‐630.
  53. Mählmann K, Koch C, Bodo G. Diagnostic endoscopy of the navicular bursa using a needle endoscope by direct or transthecal approach: a comparative cadaver study.. Vet Surg 2015;44(7):816‐824.
    doi: 10.1111/vsu.12369google scholar: lookup

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