ARTICLE
Inhibition of neointima formation by tranilast in pig coronary arteries after balloon angioplasty and stent implantation
Sugao Ishiwata, MD, FACC*,
Stefan Verheye, MD*,
Keith A. Robinson, PhD, FACC ,
Mahomed Y. Salame, MRCP*,
Hector de Leon, MD, PhD*,
Spencer B. King, III, MD, FACC* and
Nicolas A. F. Chronos, MD, FACC
* Andreas Gruentzig Cardiovascular Center, Department of Medicine (Cardiology), Emory University School of Medicine, Atlanta, Georgia, USA
Atlanta Cardiovascular Research Institute, Atlanta, Georgia, USA
Manuscript received June 29, 1999;
revised manuscript received October 27, 1999,
accepted December 15, 1999.
Reprint requests and correspondence: Dr. Nicolas Chronos, Atlanta Cardiovascular Research Institute, Suite 225, 5665 Peachtree Dunwoody Road, Atlanta, GA 30342
nchronos{at}acri.com
OBJECTIVES
We evaluated the effect of orally administered tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, on histologic and histomorphometric changes after angioplasty or stent implantation in pig coronary arteries.
BACKGROUND
Tranilast, which has antikeloid and antiallergic properties and therefore may modulate the fibrotic and inflammatory tissue responses to angioplasty and stenting, has been shown to inhibit angiographic restenosis in small clinical trials. However, its effect on histomorphometric changes in coronary arteries after angioplasty and stenting is unknown.
METHODS
Following initial pharmacokinetic studies in two pigs to determine desirable plasma levels of orally administered tranilast, 36 crossbred juvenile pigs were randomized to placebo or tranilast before undergoing balloon angioplasty in both the left anterior descending and left circumflex plus stent implantation in the right coronary artery. Oral tranilast was administered at 3 g/day starting 3 days before coronary injury and continued for 28 days until euthanasia. Injured vessels were harvested and sections analyzed by computer-assisted microscopic planimetry.
RESULTS
In balloon-injured vessels, tranilast was associated with a 37% reduction in neointimal area normalized to fracture length (0.47 ± 0.01 vs. 0.74 ± 0.03 mm; p < 0.001) and a 23% reduction in adventitial area normalized to vessel size (0.43 ± 0.02 vs. 0.56 ± 0.03; p = 0.003). In stented arteries, neointimal area normalized to injury score was 32% lower in the tranilast-treated group compared to control (1.94 ± 0.17 vs. 2.86 ± 0.29; p = 0.01).
CONCLUSIONS
In pig coronary arteries, tranilast was associated with a reduction in neointima formation and adventitial reaction after balloon injury. In stented vessels, tranilast was associated with a reduction in neointima formation normalized to injury score.
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Abbreviations and Acronyms
| | AA | = adventitial area | | FL | = fracture length | | IA | = neointimal area | | IS | = injury score | | MIT | = maximal intimal thickness | | PDGF | = platelet-derived growth factor | | PTCA | = percutaneous transluminal coronary angioplasty | | SMC | = smooth muscle cell | | TGF | = transforming growth factor | | VA | = vessel area |
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