Balloon angioplasty: Natural history of the pathophysiological response to injury in a pig model

The restenosis or occlusion that frequently follows balloon angioplasty is poorly understood. Thus, the pathophysiological response to angioplasty of the common carotid artery in 38 heparinized normal pigs was investigated by quantification of the ¹¹¹In-labeled platelet deposition and histological and electron microscopic examination from 1 hour to 60 days after angioplasty. At 1 hour, the following findings were noted: complete endothelial denudation in all arteries, marked platelet deposition (44.7 ± 20.7 x 10⁶/cm²), mural thrombus in seven of 10 pigs, and a medial tear extending through the internal elastic lamina in nine of 18 arteries. All nine arteries with tears had associated mural thrombus and severe platelet deposition (76 x 10⁶/cm²); in contrast, the nine arteries without a tear had no mural thrombus and much lower platelet depostion (6 x 10⁶/cm²). Necrosis of medial smooth muscle cells was evident at 24 hours. Platelet deposition remained high at 24 hours (40.5 ± 20.6 x 10⁶/cm²), but was markedly reduced at 4 days (4.4 ± 1.5 x 10⁶/cm²), coincident with partial growth of endothelium or periluminal lining cells. No significant platelet deposition was noted at 7 days, when the endothelial cell type of regrowth was largely complete. Intimal proliferation of smooth muscle cells was mild and patchy at 7 days, significantly greater and more uniform at 14 days, and unchanged at 30 and 60 days after angioplasty. Complete thrombotic occlusion occurred in four (11%) of the 38 pigs. A significant stenosis present at 30 days after angioplasty was shown by histological examination to be due to organization of mural thrombus. Thus, balloon angioplasty produced extensive arterial damage and was a potent stimulus for acute platelet-thrombus deposition and subsequent intimal hyperplasia. These results may have important clinical implications in the prevention of restenosis and occlusion after angioplasty.