Remodeling Rather Than Neointimal Formation Explains Luminal Narrowing After Deep Vessel Wall Injury

BACKGROUND: Oversized balloon dilatation of normal porcine coronary arteries usually heals without stenosis formation. METHODS AND RESULTS: With the purpose of developing a stenotic model and examining the mechanisms of luminal narrowing after angioplasty, we produced a circumferential deep vessel wall injury by inflating and withdrawing an oversized chain-encircled angioplasty balloon in the left anterior descending coronary artery (LAD) of 20 pigs. Three pigs died and did not complete the study. In 8 pigs (group 1), serial coronary arteriography was performed. The lumen diameter (mean+/-SD) before dilation was 3.4 +/- .4 mm; after dilation, 4.2 +/- 0.6 mm; and at follow-ups 2 and 4 weeks later, 1.6 +/- 0.4 mm (P<.0001). In 9 pigs (group 2) examined postmortem 3 weeks after dilatation, histology revealed that the injury was deep (out to adventitia) in all arteries and completely circumferential (360 degrees) in all but two arteries. Adventitia was markedly thickened as a result of neoadventitial formation. Injury correlated strongly with neointimal formation (middle LAD, r=.71, P=.00001, but neither injury nor neointima correlated with lumen size (r=.14, P=.46 and r=.34, P=.07, respectively); ie, neointimal formation did not explain late luminal narrowing. Lumen size, however, did correlate strongly with vessel size (r=.74, P=000005). The late loss in lumen diameter observed angiographically in group 1 substantially exceeded that caused by neointimal formation seen by histology in group 2. CONCLUSIONS: The chain-encircled angioplasty balloon produced a circumferential deep vessel wall injury that healed by luminal narrowing. In this porcine model, arterial remodeling was more important than neointimal formation in late luminal narrowing.