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Effect of pretreatment of ezetimibe/simvastatin on arterial healing and endothelialization after drug-eluting stent implantation in a porcine coronary restenosis model.

Sim DS, Jeong MH, Park DS, Kim JH, Lim KS, Kim HK, Kim SS, Cho JY, Jeong HC, Park KH, Hong YJ, Kim JH, Ahn Y, Cho JG, Park JC - Korean Circ J (2015)

Bottom Line: The pretreatment group (n=20) received oral ezetimibe/simvastatin (10/20 mg) daily for 7 days before stenting and the no pretreatment group (n=20) did not.There were no significant differences between the pretreatment and no pretreatment groups in the internal elastic lamina area, lumen area, neointima area, stenotic area, injury score, fibrin score, and inflammation score.In a porcine model of coronary restenosis, pretreatment with ezetimibe/simvastatin before DES implantation failed to improve arterial healing and endothelialization compared to treatment after stenting.

View Article: PubMed Central - PubMed

Affiliation: The Heart Research Center of Chonnam National University Hospital Designated by Korea Ministry of Health, Welfare and Family Affairs, Gwangju, Korea.

ABSTRACT

Background and objectives: We sought to evaluate the effect of the early use of ezetimibe/simvastatin (Vytorin®) on arterial healing and endothelialization after the implantation of a drug-eluting stent (DES) in a porcine model of coronary restenosis.

Materials and methods: A total of 20 pigs (40 coronary arteries) were randomly allocated to a pretreatment or no treatment group. The pretreatment group (n=20) received oral ezetimibe/simvastatin (10/20 mg) daily for 7 days before stenting and the no pretreatment group (n=20) did not. All pigs were treated with ezetimibe/simvastatin (10/20 mg) daily after stenting for 4 weeks. Stenting was performed using a bare-metal stent (BMS, n=10) and three types of DES: biolimus A9-eluting stent (BES, n=10), zotarolimus-eluting stent (ZES, n=10), and everolimus-eluting stents (EES, n=10). Four weeks later, pigs underwent a follow-up coronary angiography and were sacrificed for histopathologic analysis.

Results: There were no significant differences between the pretreatment and no pretreatment groups in the internal elastic lamina area, lumen area, neointima area, stenotic area, injury score, fibrin score, and inflammation score. In both groups, the fibrin score was higher in pigs with DES than in BMS, particularly in ZES and EES. The inflammatory score was not different between DES and BMS.

Conclusion: In a porcine model of coronary restenosis, pretreatment with ezetimibe/simvastatin before DES implantation failed to improve arterial healing and endothelialization compared to treatment after stenting.

No MeSH data available.


Related in: MedlinePlus

The hematoxylin-eosin stain (A-D) and Carstair's fibrin stain (E-H) (magnitude×20) by stent type in swine without ezetimibe/simvastatin pretreatment. A and E: BES, B and F: ZES, C and G: EES, D and H: BMS. Greater fibrin deposition and inflammation around the stent struts are observed in DES, compared to BMS. EES shows the most severe inflammatory cell infiltration. BES: biolimus A9-eluting stent, BMS: bare-metal stent, DES: drug-eluting stent, EES: everolimus-eluting stent, ZES: zotarolimus-eluting stent.
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Figure 2: The hematoxylin-eosin stain (A-D) and Carstair's fibrin stain (E-H) (magnitude×20) by stent type in swine without ezetimibe/simvastatin pretreatment. A and E: BES, B and F: ZES, C and G: EES, D and H: BMS. Greater fibrin deposition and inflammation around the stent struts are observed in DES, compared to BMS. EES shows the most severe inflammatory cell infiltration. BES: biolimus A9-eluting stent, BMS: bare-metal stent, DES: drug-eluting stent, EES: everolimus-eluting stent, ZES: zotarolimus-eluting stent.

Mentions: Histopathologic evaluation was conducted by an experienced cardiovascular pathologist. The specimens were embedded in methyl methacrylate and sections were cut with a low-speed diamond wafer mounted to a Buehler Isomet saw (Buehler Ltd., Lake Bluff, IL, USA). The stent wires were left intact in the cross sections to minimize potential artifacts from their removal. Fifty to 100 µm sections were obtained approximately 1 mm apart and stained with hematoxylin-eosin and Carstair's stain (Figs. 1 and 2). Measurements of the histopathologic sections were performed using a calibrated microscope, digital video imaging system, and microcomputer program (Visus 2000 Visual Image Analysis System, IMT Tech, San Diego, CA, USA). Borders were manually traced for the lumen area, the area circumscribed by the internal elastic lamina (IEL), and the innermost border of the external elastic lamina area. Morphometric analysis of the neointimal area for a given vessel was calculated as the measured IEL area minus the lumen area. The measurements were made on 5 cross sections from the proximal and distal ends and 3 midpoints of each stented segment. Histopathologic stenosis was calculated as 100×{1-(lesion lumen area/lesion IEL area)} and fibrin was identified on hematoxylin and eosin and Carstair's histochemical stained sections.


Effect of pretreatment of ezetimibe/simvastatin on arterial healing and endothelialization after drug-eluting stent implantation in a porcine coronary restenosis model.

Sim DS, Jeong MH, Park DS, Kim JH, Lim KS, Kim HK, Kim SS, Cho JY, Jeong HC, Park KH, Hong YJ, Kim JH, Ahn Y, Cho JG, Park JC - Korean Circ J (2015)

The hematoxylin-eosin stain (A-D) and Carstair's fibrin stain (E-H) (magnitude×20) by stent type in swine without ezetimibe/simvastatin pretreatment. A and E: BES, B and F: ZES, C and G: EES, D and H: BMS. Greater fibrin deposition and inflammation around the stent struts are observed in DES, compared to BMS. EES shows the most severe inflammatory cell infiltration. BES: biolimus A9-eluting stent, BMS: bare-metal stent, DES: drug-eluting stent, EES: everolimus-eluting stent, ZES: zotarolimus-eluting stent.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4372976&req=5

Figure 2: The hematoxylin-eosin stain (A-D) and Carstair's fibrin stain (E-H) (magnitude×20) by stent type in swine without ezetimibe/simvastatin pretreatment. A and E: BES, B and F: ZES, C and G: EES, D and H: BMS. Greater fibrin deposition and inflammation around the stent struts are observed in DES, compared to BMS. EES shows the most severe inflammatory cell infiltration. BES: biolimus A9-eluting stent, BMS: bare-metal stent, DES: drug-eluting stent, EES: everolimus-eluting stent, ZES: zotarolimus-eluting stent.
Mentions: Histopathologic evaluation was conducted by an experienced cardiovascular pathologist. The specimens were embedded in methyl methacrylate and sections were cut with a low-speed diamond wafer mounted to a Buehler Isomet saw (Buehler Ltd., Lake Bluff, IL, USA). The stent wires were left intact in the cross sections to minimize potential artifacts from their removal. Fifty to 100 µm sections were obtained approximately 1 mm apart and stained with hematoxylin-eosin and Carstair's stain (Figs. 1 and 2). Measurements of the histopathologic sections were performed using a calibrated microscope, digital video imaging system, and microcomputer program (Visus 2000 Visual Image Analysis System, IMT Tech, San Diego, CA, USA). Borders were manually traced for the lumen area, the area circumscribed by the internal elastic lamina (IEL), and the innermost border of the external elastic lamina area. Morphometric analysis of the neointimal area for a given vessel was calculated as the measured IEL area minus the lumen area. The measurements were made on 5 cross sections from the proximal and distal ends and 3 midpoints of each stented segment. Histopathologic stenosis was calculated as 100×{1-(lesion lumen area/lesion IEL area)} and fibrin was identified on hematoxylin and eosin and Carstair's histochemical stained sections.

Bottom Line: The pretreatment group (n=20) received oral ezetimibe/simvastatin (10/20 mg) daily for 7 days before stenting and the no pretreatment group (n=20) did not.There were no significant differences between the pretreatment and no pretreatment groups in the internal elastic lamina area, lumen area, neointima area, stenotic area, injury score, fibrin score, and inflammation score.In a porcine model of coronary restenosis, pretreatment with ezetimibe/simvastatin before DES implantation failed to improve arterial healing and endothelialization compared to treatment after stenting.

View Article: PubMed Central - PubMed

Affiliation: The Heart Research Center of Chonnam National University Hospital Designated by Korea Ministry of Health, Welfare and Family Affairs, Gwangju, Korea.

ABSTRACT

Background and objectives: We sought to evaluate the effect of the early use of ezetimibe/simvastatin (Vytorin®) on arterial healing and endothelialization after the implantation of a drug-eluting stent (DES) in a porcine model of coronary restenosis.

Materials and methods: A total of 20 pigs (40 coronary arteries) were randomly allocated to a pretreatment or no treatment group. The pretreatment group (n=20) received oral ezetimibe/simvastatin (10/20 mg) daily for 7 days before stenting and the no pretreatment group (n=20) did not. All pigs were treated with ezetimibe/simvastatin (10/20 mg) daily after stenting for 4 weeks. Stenting was performed using a bare-metal stent (BMS, n=10) and three types of DES: biolimus A9-eluting stent (BES, n=10), zotarolimus-eluting stent (ZES, n=10), and everolimus-eluting stents (EES, n=10). Four weeks later, pigs underwent a follow-up coronary angiography and were sacrificed for histopathologic analysis.

Results: There were no significant differences between the pretreatment and no pretreatment groups in the internal elastic lamina area, lumen area, neointima area, stenotic area, injury score, fibrin score, and inflammation score. In both groups, the fibrin score was higher in pigs with DES than in BMS, particularly in ZES and EES. The inflammatory score was not different between DES and BMS.

Conclusion: In a porcine model of coronary restenosis, pretreatment with ezetimibe/simvastatin before DES implantation failed to improve arterial healing and endothelialization compared to treatment after stenting.

No MeSH data available.


Related in: MedlinePlus