J Int Adv Otol 2015; 11(3): 192-5 • DOI: 10.5152/iao.2015.948
Original Article
INTRODUCTION
Myringosclerosis is an irreversible dystrophic calcification involving the fibrous layer of the tympanic membrane caused by trauma,
myringotomy, ventilation tube insertion, chronic middle ear infection, chemical agents, chronic middle ear effusion, and autoim-
munity
[1-3]
. Tympanosclerosis was first described by Zollner in 1956
[4]
. Calcium deposits are mostly seen on the tympanic mem-
brane; thus, myringosclerosis is a commonly used term during the clinical course of this disease
[5]
. Increased inflammatory reaction
and wound healing process at the fibrous layer of the tympanic membrane induce the formation of myringosclerosis
[6, 7]
.
Many factors affect the wound healing process. Extracellular matrix proteins and other molecules are important factors involved
in the course of wound healing. Glycosaminoglycan molecules are also important molecules that play important roles during the
wound healing process. Hyaluronic acid is a major glycosaminoglycan molecule, and studies have revealed that compared with
spontaneous recovery, hyaluronic acid is more effective in the healing process of the tympanic membrane, particularly in the trans-
parency of the perforated tympanic membrane. McPherson et al.
[8-10]
showed that heparin applied on the wound exerts a favorable
effect on the wound healing process.
Heparin affects multiple levels of the coagulation system. The heparin molecule contains anti-factor Xa/anti-factor IIa at a ratio of
1/1, whereas a low-molecular-weight heparin (LMWH) molecule has a higher anti-factor Xa content, with a corresponding ratio of
3/1 ratio; consequently, it affects only factor Xa. In contrast to LMWH, heparin has a negative effect on platelet aggregation. There-
fore, heparin prolongs the activated partial thromboplastin time and prothrombin time and induces undesirable bleeding episodes
during the treatment period. However, LMWH affects only factor Xa; thus, compared with heparin, undesirable bleeding episodes
are seen less frequently with LMWH
[11, 12]
.
In the light of this knowledge, we aimed to evaluate the effectiveness of enoxaparin sodium (ES), a type of LMWH, on experimen-
tally-induced myringosclerosis in rats.
Corresponding Address: İlker Akyıldız, E-mail: ilkerakyildiz@yahoo.com
Submitted: 05.06.2015 Revision received: 07.09.2015 Accepted: 22.10.2015
Copyright 2015 © The Mediterranean Society of Otology and Audiology
Effect of Enoxaparin Sodium on
Experimentally-Induced Myringosclerosis in Rats
Murat Ayata, Zeynep Kaptan, Hakkı Uzunkulaoğlu, İlker Akyıldız, Arzu Tüzüner,
Hatice Ünverdi, Hatice Karadaş
Department of Otorhinolaryngology, Ankara Training and Research Hospital, Ankara, Turkey (MA, ZK, HU, İA, AT, HK)
Department of Pathology, Ankara Training and Research Hospital, Ankara, Turkey (HÜ)
OBJECTIVE: To evaluate the effectiveness of enoxaparin sodium (ES) on experimentally-induced myringosclerosis in rats.
MATERIALS and METHODS: Twenty Wistar albino-type rats weighing up to 250–300 g each were randomized into four groups containing five rats
each and were then bilaterally myringotomized. The control group (n=5) received intratympanic serum physiologic injections, whereas ES2 (n=5),
ES4 (n=5), and ES6 groups (n=5) received intratympanic ES of 2000 IU, 4000 IU, and 6000 IU, respectively, for 10 days after myringotomy. Rats were
sacrificed at 60 days after intratympanic application and were then prepared for histopathologic evaluation.
RESULTS: As for tympanic membrane hyaline degeneration, there were statistically significant differences among the control, ES2, ES4, and ES6 groups
(p<0.05). As for fibrosis formation on tympanic membranes, a statistically significant difference was observed among the control and study groups;
however, although not statistically significant, the formation of fibrosis was slowed down in the ES2 and ES4 groups compared with the control group.
The control and study groups did not show any significant difference for calcification, hyperemia, and tympanic membrane thickening (p>0.05).
CONCLUSION: Although our study and control groups comprised limited number of animals, and only one parameter demonstrated a statistically
significant difference between the groups, ES may have an ameliorating effect on myringosclerosis induced by myringotomy in the tympanic
membranes of rats. ES proved to be effective in the prevention of hyaline disc formation. Further studies should be conducted for better under-
standing of the effects of low-molecular-weight heparin (LMWH) (i.e., enoxaparin) on myringosclerosis.
KEYWORDS: Tympanic membrane, myringosclerosis, enoxaparin sodium
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