Late Stent Thrombosis: Problem or Not? Somberg, John, MD; Weinberger, Judah, MD, PhD
The American journal of cardiology,
04/2007, Letnik:
99, Številka:
7
Journal Article
Objectives. This study examined the effects of intracoronary Irradiation on neointimal proliferation after overstretch balloon angioplasty in a normolipemic swine model of restenosis.
Background. ...Restenosis after percutaneous transluminal coronary angioplasty represents, in part, a proliferative response of vascular smooth muscle at the site of injury. We have previously shown that ionizing radiation, delivered by means of an intracoronary source, causes focal medial fibrosis. We therefore hypothesized that ntracoronary irradiation delivered at the time of balloon angtoplasty might impair the restenosis process.
Methods. Nineteen juvenile swine underwent coronary angiography; a segment of the coronary artery was chosen as a target for balloon injury. In 10 swine, a ribbon of iridiun-192 was positioned at the target segment, and 2,000 cGy was delivered at the vessel wall. Subsequently, overdilation balloon angioplasty was perfromed at the irradiated segment. In nine control swine, overdilation balloon angioplasty was performed without previous irradiation. Eighteen animals survived and were killed at 30 days. Histopathologic analysis was performed by a pathologist in blinded manner. The area of maximal lumen compromise within the target segment was analyzed by computer-assisted planimetry.
Results. In the control group, mean (± SD) neointimal area was 0.84 ± 0.60 mm2compared with that in the irradiated group, 0.24 ± 0.13 mm2(p = 0.01). In the control group, mean percent area stenosis was 47.6 ± 20.7%, whereas that in the irradiated group was 17.6 ± 10.5% (p = 0.001). This represents a 71.4% reduction in neointimal area and a 63.0% reduction in percent area stenosis in the irradiated group. Adjacent coronary segments and surrounding myocardium were unaffected.
Conclusions. Intracoronary irradiation (2,000 cGy) delivered to a target porcine coronary segment before balloon overdilation markedly reduces neointima formation at 30 days and thus significantly impairs the restenosis process.
This study examined the long-term efficacy of intracoronary irradiation for limiting neointimal proliferation after overstretch balloon angioplasty in a porcine model of restenosis. In addition, this ...study sought to identify any adverse late sequelae of this novel therapy for restenosis.
Restenosis after coronary angioplasty represents in part a proliferative response of vascular smooth muscle at the site of injury. We have shown previously that high dose intracoronary radiation induces focal medial fibrosis and markedly reduces neointimal proliferation early after balloon angioplasty in swine.
Twenty-two juvenile swine underwent intervention at a target segment of the left coronary artery. In 11 swine, a 2-cm ribbon of iridium-192 was positioned at the target segment and 2,000 cGy was delivered to the vessel wall. Subsequently, overdilation balloon angioplasty was performed at the irradiated segment. In 11 control swine, overdilation balloon angioplasty was performed without previous irradiation. Twenty animals survived and underwent histopathologic analysis at 180 ± 8 days.
Mean (±SD) neointimal area was 1.59 ± 0.78 and 0.46 ± 0.35 mm2(p < 0.001) in control and irradiated animals, respectively. Mean percent area stenosis was 37.9 ± 12.4% and 14.2 ± 9.0% (p < 0.001) in the control and irradiated animals, respectively. Thus, by 6-month follow-up, intracoronary irradiation before balloon angioplasty had reduced the bulk of the neointimal lesion by 71.1% and reduced percent area stenosis by 62.5% compared with that in control animals. There was no evidence of radiation vasculopathy or myocardial damage at 6 months.
Intracoronary irradiation (2,000 cGy) produces persistent impairment of neointimal proliferation 6 months after balloon injury, with no evidence of late radiation sequelae.
Coronary drug-eluting stents are commonplace in clinical practice with acceptable safety and efficacy. Preclinical evaluation of novel drug-eluting stent technologies has great importance for ...understanding safety and possibly efficacy of these technologies, and well-defined preclinical testing methods clearly benefit multiple communities within the developmental, testing, and clinical evaluation chain. An earlier consensus publication enjoyed widespread adoption but is in need of updating. This publication is an update, presenting an integrated view for testing drug-eluting technologies in preclinical models, including novel devices such as bioabsorbable coatings, totally bioabsorbable stents, bifurcation stents, and stent-free balloon-based drug delivery. This consensus document was produced by preclinical and translational scientists and investigators engaged in interventional technology community. The United States Food and Drug Administration (USFDA) recently issued a Draft Guidance for Industry Document for Drug-Eluting Stents. This expert consensus document is consistent with the Food and Drug Administration guidance. The dynamic nature of this field mandates future modifications and additions that will be added over time.
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