Background: Mechanisms of stenosis after angioplasty are often studied in experimental models created by injury of normal arteries. Sequential rather than single insult may provide the better model. We compared the response of arteries to these two types of injury.
Methods: Two groups of arteries of cholesterol-fed New Zealand white rabbits were compared: single balloon injury arteries and two sequential balloon injury arteries (14-day interval between injuries). At 1-49 days after the first injury lumen dimensions and number of cells and cell proliferation in the media and neointima were assessed.
Results: Single injury resulted in cell proliferation in the artery wall, formation of neointimal, and progressive loss of lumen diameter. In sequentially injured arteries, the second injury caused an immediate increase in angiographic lumen diameter from 1.6 +/- 0.1 mm to 2.0 +/- 0.1 mm but the lumen decreased to 1.3 +/- 0.3 mm by 28 days after the second injury, consistent with restenosis. At late time points after injury the lumen diameter was similar in the two groups of arteries. The sequential lesion neointimal area increased at the same rate as the primary lesion neointimal. The second of the sequential injuries stimulated cell proliferation activity in the vessel wall that was similar in magnitude to that seen after primary injury.
Conclusions: These findings suggest that the primary injury process initiated mechanisms that determine the rate of neointimal area formation and lumen dimensions over the 5-6 week time interval studied here. The second of the sequential injuries initiated a cell proliferation response in the artery wall but did not alter the neointimal area or lumen caliber consequences of primary injury.