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The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model [Anatol J Cardiol]
Anatol J Cardiol. 2011; 11(2): 93-100 | DOI: 10.5152/akd.2011.026  

The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model

Mehmet Güzeloğlu1, Mehmet Gül2, Buket Reel3, İsmail Yürekli4, Koray Aykut5, Eyüp Hazan6
1Department of Cardiovascular Surgery, Faculty of Medicine, Mustafa Kemal University, Hatay
2Clinic of Cardiology, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, İstanbul-Turkey
3Department of Pharmacology, Faculty of Pharmacy, Ege University, İzmir
4İzmir Atatürk Eğitim ve Araştırma Hastanesi, Kalp ve Damar Cerrahisi Kliniği, İzmir, Türkiye
5Cardiovascular Surgery Clinics, Ege Hospital, Denizli
6Department of Cardiovascular Surgery, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey

Objective: The aim of the present study was to investigate the effect of zoledronic acid (ZA), as a matrix metalloproteinase inhibitor, on neointimal hyperplasia in rabbit carotid anastomosis model. Methods: New Zealand male rabbits were divided into two groups as placebo and treatment groups in this experimental study. After anesthesia, the right carotid artery of each rabbit was end-to-end anastomosed with an 8/0 polypropylene suture. Left carotid artery was kept as control without any operation. Placebo group (n=6) received phosphate buffered saline (PBS) (0.5mL/kg/day/s.c.) for 28 days postoperatively, whereas ZA group (n=6) received ZA (100 µg/kg/day/s.c.) for the same period. After sacrification, the anastomosed and control arteries were isolated. Morphometric and immunohistochemical examinations were performed. Statistical analyses of morphometric and immunohistochemical data were performed using two-way ANOVA and Chi-square test respectively. Results: In PBS group, vascular injury in the anastomosed artery significantly increased the intimal area (anastomosed: 112.51±61.18 µm2*1000 vs. control: 22.62±4.26µm2*1000, p<0.01) and intima/media index (anastomosed: 0.347±0.29 vs. control: 0.075±0.01, p<0.05) compared to control artery. ZA significantly reduced the intimal area (39.29±18.21 µm2*1000, p<0.01) and intima/media index (0.112±0.07, p<0.05) compared to PBS group. Additionally, α-smooth muscle actin immunopositivity was found significantly decreased in anastomosed arteries from ZA group (ZA: 2.33±0.52 vs. PBS: 3.50±0.5, p<0.05). Moreover, intensive gelatinase (MMP-2 and MMP-9) immunoreactivities were clearly seen in anastomosed arteries compared to control arteries from PBS group. ZA apparently decreased immunopositivities for gelatinases in anastomosed arteries. Conclusion: ZA might be a promising agent for prevention of neointimal hyperplasia, which is the most significant cause of graft failures in late postoperative period.

Keywords: Neointimal, matrix metalloproteinases (MMPs), zoledronic acid, rabbit


Mehmet Güzeloğlu, Mehmet Gül, Buket Reel, İsmail Yürekli, Koray Aykut, Eyüp Hazan. The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model. Anatol J Cardiol. 2011; 11(2): 93-100


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