Document Detail

The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model.
MedLine Citation:
PMID:  21285021     Owner:  NLM     Status:  MEDLINE    
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 µm(2)*1000 vs. control: 22.62±4.26 µm(2)*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 µm(2)*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.
Mehmet Güzeloğlu; Mehmet Gül; Buket Reel; Ismail Yürekli; Koray Aykut; Eyüp Hazan
Publication Detail:
Type:  Journal Article     Date:  2011-02-02
Journal Detail:
Title:  Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology     Volume:  11     ISSN:  1308-0032     ISO Abbreviation:  Anadolu Kardiyol Derg     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-07     Completed Date:  2012-01-05     Revised Date:  2012-01-19    
Medline Journal Info:
Nlm Unique ID:  101095069     Medline TA:  Anadolu Kardiyol Derg     Country:  Turkey    
Other Details:
Languages:  eng     Pagination:  93-100     Citation Subset:  IM    
Department of Cardiovascular Surgery, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey.
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MeSH Terms
Actins / analysis
Anastomosis, Surgical
Carotid Arteries / pathology,  surgery*
Diphosphonates / pharmacology,  therapeutic use*
Disease Models, Animal
Hyperplasia / drug therapy,  prevention & control
Imidazoles / pharmacology,  therapeutic use*
Matrix Metalloproteinase 2 / analysis
Matrix Metalloproteinase 9 / analysis
Matrix Metalloproteinases / analysis,  antagonists & inhibitors*
Muscle, Smooth, Vascular / chemistry,  enzymology,  pathology
Neointima / drug therapy,  pathology,  prevention & control*
Random Allocation
Reg. No./Substance:
0/Actins; 0/Diphosphonates; 0/Imidazoles; 118072-93-8/zoledronic acid; EC 3.4.24.-/Matrix Metalloproteinases; EC Metalloproteinase 2; EC Metalloproteinase 9

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