Cilostazol as a noninferiority pharmacologic option to paclitaxel in early intimal hyperplasia inhibition after venous balloon angioplasty in a rabbit model: a preliminary study

Background Flow diverters (FDs) are an effective treatment for intracranial aneurysms, though not free from hemorrhagic complications. A previous study demonstrated increased vascular contractility after FD-implantation as a potential mechanism of distal complications. Our study aimed to investigate whether L-arginine medication affects vascular contractility following FD deployment in a rabbit model. Methods FDs were implanted in the aorta of normal rabbits (+FD, n = 10), with sham-operated aorta as controls (n = 5). L-Arginine was given in the drinking water (2.25% L-arginine hydrochloride) of half of the +FD animals (+FD/+Arg). Force contraction vascular contractility studies were performed on the aortic rings proximal and distal to the FD using an organ bath. Total eNOS, eNOS(pS1177), eNOS(pT495), COX-2, and S100A4 were quantified by western analysis on total protein lysates from aortic segments, normalizing to GAPDH. Results Mean vascular contractility was 53% higher in distal relative to proximal aortic segments (P = 0.0038) in +FD animals, but were not significantly different in +FD/+Arg animals, or in sham-operated controls. The +FD animals expressed significantly reduced levels of eNOS(pS1177) than sham-operated controls (P = 0.0335), while both the +FD and +FD/+Arg groups had reduced levels of eNOS(pT495) relative to sham-operated controls (P = 0.0331 and P = 0.0311, respectively). Conclusion These results suggest that L-arginine medication reduces distal vascular contractility after FD treatment via nitric oxide production and thus might mitigate risk for downstream complications.

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Abstract 117: Heparin Derived Oligosaccharide Inhibits Vascular Intimal Hyperplasia in Balloon Injured Carotid Artery and the Mechanism Involved

Circulation Research ◽

10.1161/res.117.suppl_1.117 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

He Shuying ◽

Wu Jie

Keyword(s):

Growth Factor ◽

Carotid Artery ◽

Common Carotid Artery ◽

Intimal Hyperplasia ◽

Serum Lipids ◽

Rabbit Model ◽

High Cholesterol Diet ◽

Type I ◽

Monocyte Chemoattractant Protein 1 ◽

Expression Levels

To determine the effects of heparin-derived oligosaccharides (HDOs) on vascular intimal hyperplasia (IH) in balloon-injured carotid artery and the mechanism involved. The animal model was established by rubbing the endothelia within the common carotid artery (CCA) of male rabbits along with a high-cholesterol diet. The arterial IH was testified by histopathological changes of the CCA. Serum lipids were detected using automated biochemical analysis; Expression of mRNAs corresponding to vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter A1 (ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were detected by western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and bFGF. The results implied that administration of HDO significantly inhibited common carotid artery histopathology and restenosis that was induced by balloon injury. Treatment with HDO also significantly decreased mRNA and protein expression levels of VEGF, bFGF, VCAM-1, MCP-1, and SR-BI in the arterial wall, however ABCA-1 expression levels were elevated. HDO treatment led to a reduction in various serum lipids (total cholesterol, triglycerides, high-density and low-density lipoproteins). We concluded that, in a rabbit model, HDO can ameliorate IH and the mechanisms might involved VEGF, bFGF, VCAM-1, MCP-1, SR-BI and ABCA-1.

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Radioimmunoscintigraphic approach for the in vivo detection of tuberculomas—A preliminary study in a rabbit model

International Journal of Radiation Applications and Instrumentation Part B Nuclear Medicine and Biology ◽

10.1016/0883-2897(92)90184-z ◽

1992 ◽

Vol 19 (1) ◽

pp. 45-53 ◽

Cited By ~ 4

Author(s):

Basant L. Malpani ◽

Gururaj V. Kadival ◽

Aban M. Samuel

Keyword(s):

Rabbit Model ◽

In Vivo Detection ◽

Preliminary Study

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Extracellular matrix remodeling after balloon angioplasty injury in a rabbit model of restenosis.

Circulation Research ◽

10.1161/01.res.75.4.650 ◽

1994 ◽

Vol 75 (4) ◽

pp. 650-658 ◽

Cited By ~ 154

Author(s):

B H Strauss ◽

R J Chisholm ◽

F W Keeley ◽

A I Gotlieb ◽

R A Logan ◽

...

Keyword(s):

Extracellular Matrix ◽

Balloon Angioplasty ◽

Rabbit Model ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling

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L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty.

Arteriosclerosis and Thrombosis A Journal of Vascular Biology ◽

10.1161/01.atv.14.6.938 ◽

1994 ◽

Vol 14 (6) ◽

pp. 938-943 ◽

Cited By ~ 66

Author(s):

W C Tarry ◽

R G Makhoul

Keyword(s):

Balloon Angioplasty ◽

Intimal Hyperplasia

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Percutaneous delivery of the gax gene inhibits vessel stenosis in a rabbit model of balloon angioplasty

Cardiovascular Research ◽

10.1016/s0008-6363(97)00147-8 ◽

1997 ◽

Vol 35 (3) ◽

pp. 536-546 ◽

Cited By ~ 47

Author(s):

L Maillard

Keyword(s):

Balloon Angioplasty ◽

Rabbit Model ◽

Vessel Stenosis

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NO synthesis is involved in structural and functional effects of ACE inhibitors in injured arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.270.1.h298 ◽

1996 ◽

Vol 270 (1) ◽

pp. H298-H305 ◽

Cited By ~ 1

Author(s):

E. Van Belle ◽

B. Vallet ◽

J. L. Auffray ◽

C. Bauters ◽

M. Hamon ◽

...

Keyword(s):

Endothelial Cells ◽

Ace Inhibitors ◽

Intimal Hyperplasia ◽

Vascular Function ◽

Ace Inhibitor ◽

White Male ◽

Rabbit Model ◽

Balloon Injury

Angiotensin-converting enzyme (ACE) inhibitors reduce intimal hyperplasia after balloon injury. A role for nitric oxide (NO) has been suggested in this effect. Because recent data suggest that NO may modulate some features of endothelial cells and because endothelial cells are involved in the control of intimal hyperplasia, we investigated the role of NO synthesis in the effect of an ACE inhibitor, perindopril, on neoendothelial dysfunction and intimal hyperplasia in a rabbit model of unilateral iliac balloon injury. New Zealand White male rabbits received placebo, perindopril, or cotreatment with perindopril and NG-nitro-L-arginine methyl ester (L-NAME) and were evaluated 4 wk after the injury. Fifteen rabbits (5 in each group) were used to assess in vitro vasoreactivity and twenty-four (8 in each group) for morphometric analysis. In injured vessels, neoendothelium-dependent relaxation in ACE inhibitor-treated animals was improved compared with placebo (P < 0.05) and restored to the level of noninjured vessels (NS). The improvement observed with ACE inhibitor was abolished by cotreatment with L-NAME (P < 0.05). In the same vessels, no effect was observed on neoendothelium-independent vasoreactivity. The improved neoendothelial dysfunction with ACE inhibitor was associated with a 66% reduction in intimal thickening (P < 0.01). The effect was also reversed by cotreatment with L-NAME (P < 0.01). In noninjured vessels, treatment did not alter vasoreactivity or morphology of the vessel wall. These results suggest that NO synthesis may play a key role in the improvement of vascular function seen with ACE inhibitor in balloon-injured vessels.

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