Effectiveness of Methylene Blue in the Prevention of Stifle Joint Arthrofibrosis in Rabbit Models

Document Type : RESEARCH PAPER

Authors

1 Bone and Joint Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: One of the major challenges in orthopedic surgery is the prevention of arthrofibrosis, which can be
successfully alleviated in its early stages. Many studies suggest the administration of methylene blue (MB) as an
accessible and effective agent for the prevention of post-operation adhesions. The purpose of this study was to evaluate
the efficacy of MB in the prevention of arthrofibrosis.
Methods: This study was conducted on 18 New Zealand white female mature rabbits. The anterior cruciate ligament
of the left stifle joint of each animal was cut during aseptic surgery. In the next step, the rabbits were divided into three
groups based on their treatments. The rabbits in the first, second, and third groups were subjected to the injection of
normal saline, 1% MB solution, and 2% MB solution into their synovial space, respectively. The postoperative stifle
range of motion was measured every week. After 4 weeks, the animals were euthanized and all joints were dissected
for histopathology.
Results: The histopathological evaluation of tissues indicated the presence of fibrotic connective tissue as a sign of
fibrosis in all groups. The fibrosis rate, inflammatory rate, tissue disarrangement, fibroblastic cellularity, and granulation
tissue formation were at their highest levels in the 1% MB group. The integrity of articular cartilage in the 2% MB group
was lower than the other groups. The level of bone degeneration was similar in both MB groups; however, it was more
than the control saline group. The range of motion was reduced during the first week, then increased in the second and
third weeks, and finally decreased in the fourth week.
Conclusion: The MB was not an effective method regarding the prevention or treatment of arthofibrosis and the
subsequent osteoarthritis. In contrast with previous studies, fibrosis was lower in the high dose MB group, compared
to the low dose MB group. The alterations in the range of motion were related to the reduced movement caused by the
pain and stiffness of the operated joints. The current study can be considered as the first report addressing the adverse
effect of MB on synovial components.

Keywords

Main Subjects

References

1. Noyes FR, Mangine RE, Barber S. Early knee motion
after open and arthroscopic anterior cruciate
ligament reconstruction. Am J Sports Med. 1987;
15(2):149-60.
2. Noyes FR, Wojtys EM, Marshall MT. The early
diagnosis and treatment of developmental patella
infera syndrome. Clin Orthop Relat Res. 1991;
265(1):241-52.
3. Cetin M, Duran B, Demirkoprulu N, Guvenal T, Erden
O, Cetin A. Effects of diazeniumdiolates (NONOates)
and methylene blue on the reduction of postoperative
adhesion in rats. Gynecol Obstet Invest. 2004;
57(4):186-90.
4. Dinc S, Ozaslan C, Kuru B, Karaca S, Ustun H, Alagol
H, et al. Methylene blue prevents surgery-induced
peritoneal adhesions but impairs the early phase
of anastomotic wound healing. Can J Surg. 2006;
49(5):321-8.
5. Galili Y, Ben-Abraham R, Rabau M, Klausner J,
Kluger Y. Reduction of surgery-induced peritoneal
adhesions by methylene blue. Am J Surg. 1998;
175(1):30-2.
6. Heydrick SJ, Reed KL, Cohen PA, Aarons CB, Gower
AC, Becker JM, et al. Intraperitoneal administration of
methylene blue attenuates oxidative stress, increases
peritoneal fibrinolysis, and inhibits intraabdominal
adhesion formation. J Surg Res. 2007; 143(2):311-9.
7. Kluger Y, Weinbroum A, Ben-Avraham R, Galili Y,
Klausner J, Rabau M. Reduction in formation of
peritoneal adhesions by methylene blue in rats: a
dose response study. Eur J Surg. 2000; 166(7):568-71.
8. Yildiz H, Durmus AS, Simsek H, Yaman I. The
comparison of methylene blue and vitamin E in
prevention of abdominal postoperative adhesion
formation in rat uterine horn models: biochemical
and histopathologic evaluation. Acta Cir Bras. 2011;
26(1):51-7.
9. Farrokhi MR, Vasei M, Fareghbal S, Farrokhi N.
The effect of methylene blue on peridural fibrosis
formation after laminectomy in rats: an experimental
novel study. Spine J. 2011; 11(2):147-52.
10. Namazi H. Botulinum toxin as a novel addition to
anti-arthritis armamentarium: an experimental
study in rabbits. Int Immunopharmacol. 2006;
6(11):1743-7.
11. Namazi H, Torabi S. Novel use of botulinum toxin to
ameliorate arthrofibrosis: an experimental study in
rabbits. Toxicol Pathol. 2007; 35(5):715-8.
12. Seydi N, Dehghani S. Radiological study of the effect
of Platelet Rich Plasma (PRP) on experimentally
induced osteoarthritis in Guinea Pig’s stifle joint. J
Animal Poultry Sci. 2013; 2(3):73-8.
13. Toghraie FS, Chenari N, Gholipour MA, Faghih
Z, Torabinejad S, Dehghani S, et al. Treatment of
osteoarthritis with infrapatellar fat pad derived
mesenchymal stem cells in Rabbit. Knee. 2011;
18(2):71-5.
14. National Toxicology Program. Toxicology and
carcinogenesis studies of methylene blue trihydrate
(Cas No. 7220-79-3) in F344/N rats and B6C3F1
mice (gavage studies). Natl Toxicol Program Tech Rep
Ser. 2008; 540(1):1-224.
15. Luna LG. Manual of histologic staining methods of
the armed forces institute of pathology. 3rd ed. New
York: Blakiston Division, McGraw-Hill; 1968.
16. Aydin E, Uckan S, Ozdemir BH, Uyar P. Mitomycin
C effect on fibrous adhesions of rabbit
temporomandibular joint. Otolaryngol Head Neck
Surg. 2005; 133(5):672-6.
17. Brunelli G, Longinotti C, Bertazzo C, Pavesio A,
Pressato D. Adhesion reduction after knee surgery
in a rabbit model by hyaloglide®, a hyaluronan
derivative gel. J Orthop Res. 2005; 23(6):1377-82.
18. Emami MJ, Jaberi FM, Azarpira N, Vosoughi
AR, Tanideh N. Prevention of arthrofibrosis by
monoclonal antibody against vascular endothelial
growth factor: a novel use of bevacizumab in rabbits.
Orthop Traumatol Surg Res. 2012; 98(7):759-64.
19. Kocaoglu B, Akgun U, Nalbantoglu U, Poyanlı O,
Karahan M. Adhesion reduction after knee surgery
in a rat model by mitomycin C. Knee Surg Sports
Traumatol Arthrosc. 2011; 19(1):94-8.
20. Zhao S, Sun Y, Li X, Wang J, Yan L, Chen H, et al.
Reduction of intraarticular adhesion of knee by local
application of rapamycin in rabbits via inhibition
of fibroblast proliferation and collagen synthesis. J
Orthop Surg Res. 2016; 11(1):45.
21. Johnson R, Zenhausen A, Zollinger H, Mark H, Mcketta
J. Krik-Othmer encyclopedia of chemical technology.
New York: Wiley, Hoboken; 1978. P. 379.
22. Lide DR. CRC handbook of chemistry and physics.
Florida: CRC Press; 2004.
23. Osol A, Remington JP. Remington’s pharmaceutical
sciences. North Carolina: Mack; 1980.
24. American Society of Hospital Pharmacists. American
hospital formulary service drug information.
Maryland: Authority of the Board of Directors of the
American Society of Hospital Pharmacists; 1994.
25. Sunshine I. Handbook of analytical toxicology.
Florida: CRC Press; 1969. P. 77.
26. Aksu B, Inan M, Kanter M, Oz Puyan F, Uzun H,
Durmus-Altun G, et al. The effects of methylene
blue on renal scarring due to pyelonephritis in rats.
Pediatr Nephrol. 2007; 22(7):992-1001.
27. Demirbilek S, Sizanli E, Karadag N, Karaman
A, Bayraktar N, Turkmen E, et al. The effects of
methylene blue on lung injury in septic rats. Eur Surg
Res. 2006; 38(1):35-41.
28. Mentes BB, Akin M, Leventoglu S, Gultekin FA,
Oguz M. Intradermal methylene blue injectionfor
the treatment of intractable idiopathic pruritus
ani:results of 30 cases. Tech Coloproctol. 2004;
8(1):11-4.
29. Miclescu A, Basu S, Wiklund L. Methylene blue added
to a hypertonic–hyperoncotic solution increases
short-term survival in experimental cardiac arrest.
Crit Care Med. 2006; 34(11):2806-13.
30. O’Neil MJ. The merck index an encylopedia of
chemiclas, drugs and biologicals: Cambridge: RSC
Publishing; 2006.
31. Peng B, Zhang Y, Hou S, Wu W, Fu X. Intradiscal
methylene blue injection for the treatment of
chronic discogenic low back pain. Eur Spine J. 2007;
16(1):33-8.
32. Sharr MM, Weller RO, Brice JG. Spinal cord necrosis
after intrathecal injection of methylene blue. J Neurol
Neurosurg Psychiatry. 1978; 41(4):384-6.
33. Sutherland AD, Faragher IG, Frizelle FA. Intradermal
injection of methylene blue for the treatment
of refractory pruritus ani. Colorectal Dis. 2009;
11(3):282-7.
34. Wainwright M, Crossley K. Methylene blue--a
therapeutic dye for all seasons? J Chemother. 2002;
14(5):431-43.
35. Salaris SC, Babbs CF, Voorhees WD 3rd. Methylene
blue as an inhibitor of superoxide generation
by xanthine oxidase. A potential new drug for
the attenuation of ischemia/reperfusion injury.
Biochem Pharmacol. 1991; 42(3):499-506.
36. Noyes FR, DeLucas JL, Torvik PJ. Biomechanics of
anterior cruciate ligament failure: an analysis of
strain-rate sensitivity and mechanisms of failure in
primates. J Bone Joint Surg Am. 1974; 56(2):236-53.
37. Weiler A, Förster C, Hunt P, Falk R, Jung TM,
Unterhauser FN, et al. The influence of locally
applied platelet-derived growth factor-BB on free
tendon graft remodeling after anterior cruciate
ligament reconstruction. Am J Sports Med. 2004;
32(4):881-91.
38. Kalbkhani M, Dehghani S, Najafpour A, Ghorbanzadeh
N. The effect of autogenous platelet rich plasma on
experimentally induced osteoarthritis in rabbit’s
stifles joint: a radiological assessment. J Animal
Poultry Sci. 2013; 2(1):27-38.
The Archives of Bone and Joint Surgery
Volume 7, Issue 3
May 2019
Pages 269-277

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History

  • Receive Date: 12 August 2017
  • Revise Date: 13 October 2018
  • Accept Date: 04 April 2018

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