Inhibition of neointima formation by tranilast in pig coronary arteries after balloon angioplasty and stent implantation.
OBJECTIVE
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.
Ishiwata
S
S
Andreas Gruentzig Cardiovascular Center, Department of Medicine (cardiology), Emory University School of Medicine, Atlanta, Georgia, USA.
Verheye
S
S
Robinson
K A
KA
Salame
M Y
MY
de Leon
H
H
King
S B
SB
Chronos
N A
NA
D000284:Administration, Oral; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation; D000818:Animals; D018926:Anti-Allergic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003327:Coronary Disease / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003331:Coronary Vessels / Q000293:injuries*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005355:Fibrosis; D007249:Inflammation; D008297:Male; D011897:Random Allocation; D012008:Recurrence; D015607:Stents / Q000009:adverse effects*; D013552:Swine; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries*; D014945:Wound Healing / Q000187:drug effects; D014947:Wounds and Injuries / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D062367:ortho-Aminobenzoates / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
D018926:Anti-Allergic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D062367:ortho-Aminobenzoates; C012293:tranilast