Balloon angioplasty—Natural history of the pathophysiological response to injury in a pig model: Steele PM, Chesebro JH, Stanson AW, et al. Circulation 1985; 57:105-12

Abstract

This article reviews the histopathologic responses that were seen after balloon angioplasty of the carotid arteries was performed in a series of normal nonatherosclerotic pigs. A standard balloon angioplasty was performed. Intraoperative heparinization was used but antiplatelet agents were not. The animals were put to death over varying periods between 1 hour and 60 days after dilation and the carotid arteries were immediately fixed in situ with a glutaraldehyde solution. Labeled autologous platelets were administered to the animals 18 to 24 hours before death. Harvested specimens were then examined for evidence of wall injury, platelet and thrombus deposition, and smooth muscle cell proliferation. Angioplasty consistently produced complete endothelial denudation and the subintima in these areas was regularly coated with a layer of adherent platelets within 1 hour of the procedure. Endothelial regrowth was partial within 4 days and generally complete within 7 days, with a parallel reduction in platelet deposition such that there was no significant platelet deposition after 1 week. Fifty percent of the arteries examined at 1 hour revealed tears extending from the luminal surface to varying depths into the media. Platelet deposition was invariably heaviest in these arteries and, in addition, there was invariably associated macroscopic mural thrombus. In 11% of the animals the mural thrombus eventually resulted in complete occlusion within the 60-day study period. Mural thrombi, which were seen in animals killed after 7 days, demonstrated fibrous organization, with frequent associated significant stenosis. Intimal proliferation of smooth muscle cells was apparent within 7 days and increased to a stable level by 14 days. The authors have noted that the acute changes they have produced in the normal nonatherosclerotic pig artery are similar to and less severe than those produced in the atherosclerotic patient. As expected, platelet deposition was directly related to the degree of denudation of the intima and the enhanced platelet deposition and mural thrombus formation seen in arteries with deeper injuries was related to the enhanced thrombogenic potential of the exposed media, as well as the lower levels of prostacyclin found in the deeper layers of the arterial wall. This study suggests that recurrent stenosis occurring later after angioplasty may be the result of organization of early mural thrombus that eventually develops histologic features identical to that of a fibrous plaque, or by the stimulation of smooth muscle proliferation in the intima, or by a combination of the two.