The Effect of Endovascular Irradiation on Platelet Recruitment at Sites of Balloon Angioplasty in Pig Coronary Arteries

Salame, Mahomed Y.; Verheye, Stefan; Mulkey, Stephen P.; Chronos, Nicolas; King, Spencer B.; Crocker, Ian; Robinson, Keith A.

doi:10.1161/01.cir.101.10.1087

Cited by 49 publications

(31 citation statements)

References 14 publications

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“…4 -6 We previously documented a significant increase in platelet recruitment and a larger thrombus area at 1 month in injured irradiated vessels compared with nonirradiated injured arteries in adult miniature pigs. 22 The current experiments showed that, unlike nonirradiated arteries in which a complete resolution of thrombus and thin neointima was seen by 6 months, thrombus persisted in irradiated arteries and neointima was augmented.…”

Section: Summary Of Histomorphometry Datamentioning

confidence: 49%

Intracoronary β-Radiation Exacerbates Long-Term Neointima Formation in Balloon-Injured Pig Coronary Arteries

Coussement¹,

León²,

Ueno³

et al. 2001

Circulation

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Background Long-term biological effects of ionizing radiation on coronary arteries remain poorly defined. We examined late arterial responses 6 months after balloon angioplasty and β-radiation in normal pig coronary arteries. Methods and Results Coronary arteries of 25 adult pigs were randomized to receive 20 Gy (n=8) or 30 Gy (n=9) of 186 Re β-radiation or sham radiation (n=8) immediately after balloon angioplasty. Aspirin was given daily during follow-up. The study vessels were analyzed histopathologically at 6 months. β-Radiation decreased lumen area (20 Gy, 1.55±0.99 mm 2 ; 30 Gy, 1.03±0.82 mm 2 ; and 0 Gy, 2.05±0.80 mm 2 ; P <0.05) but not overall vessel area. The neointimal area was significantly larger within the injured segment with β-radiation (20 Gy, 1.92±1.23 mm 2 ; 30 Gy, 1.51±0.97 mm 2 ; and 0 Gy, 0.89±0.31 mm 2 ; 0 Gy versus 20 Gy, P <0.05), and a significant increase of edge stenosis was observed with β-radiation. Irradiated vessels also had larger thrombus areas within the neointima (30 Gy, 0.24±0.61 mm 2 ; 20 Gy, 0.98±1.57 mm2; and 0 Gy, 0.00±0.01 mm 2 ; P <0.05) and larger adventitial areas (20 Gy, 2.25±0.75 mm 2 ; 30 Gy, 2.38±0.98 mm 2 ; and 0 Gy, 1.23±0.29 mm 2 ; 0 Gy versus 20 or 30 Gy, P <0.05) that showed substantial collagen accumulation. Conclusions Intracoronary β-radiation did not inhibit neointima formation in balloon-injured normal pig coronary arteries 6 months after the interventional procedure. Unresorbed thrombus contributed to, but was not the sole component of, augmented neointima formation. Irradiated vessels demonstrated more adventitial thickening and fibrosis. These observations may have relevance for long-term clinical outcomes after intracoronary β-radiation.

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Section: Summary Of Histomorphometry Datamentioning

confidence: 49%

Intracoronary β-Radiation Exacerbates Long-Term Neointima Formation in Balloon-Injured Pig Coronary Arteries

Coussement¹,

León²,

Ueno³

et al. 2001

Circulation

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“…8,9 The release of vasoconstrictive mediators from activated platelets may also be a mechanism that could contribute to the development of arterial spasm.…”

Section: Discussionmentioning

confidence: 99%

High-Dose Intravascular β-Radiation After De Novo Stent Implantation Induces Coronary Artery Spasm

et al. 2002

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Background-Intracoronary brachytherapy is effective in preventing restenosis after coronary interventions. However, in vitro and animal studies have shown that irradiation produces immediate and sustained endothelial dysfunction. This study assesses the clinical relevance of impaired vasomotoric function induced by brachytherapy. Methods and Results-We analyzed the occurrence of postradiation coronary artery spasms in 1 animal study and 2 clinical trials investigating the effects of high-dose intracoronary ␤-radiation after de novo coronary artery stenting. Irradiated segments (IRSs) proximal and distal to the stent were studied by quantitative coronary angiography after stenting, after radiation, and at the end of the procedure. There was an 67% overall incidence of coronary artery spasm in the IRSs immediately after ␤-radiation compared with 9% after sham treatment (PϽ0.001). Whereas in most cases this phenomenon was only minor or moderate, in 12 cases, 4 (22%) animals and 8 (28%) patients, severe coronary spasm (Ͼ90% diameter stenosis) with significant ECG-changes or hemodynamic instability was observed. Relief of spasms was protracted (mean time until complete relief of spasm 423Ϯ122 seconds) and required repetitive intracoronary administration of nitroglycerin (mean dose: 1.2Ϯ0.6 mg). Conclusions-Vasoconstriction is a frequent reaction of coronary arteries after high-dose intracoronary ␤-radiation, necessitating repetitive administration of vasodilators.

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“…A later study in adult Yucatan miniature pigs by Salame, et al found that coronary arteries irradiated at 15 or 30 Gy at 2 mm from the 90 Sr / Y source had areas within the injured segment that had not been fully re-endothelialized by 1 month and this was associated with a significant increase in platelet recruitment at the angioplasty site compared to balloon injured non-irradiated controls even at 1 month post injury. 80) Additionally, Waksman, et al investigated potential mechanisms of the radiation effects detected as suppression of neointima formation and inhibition of post-angioplasty vessel chronic constriction. 81,82) Cell proliferation, as detected by quantitative immunohistochemistry for incorporated BrdU, was found to be significantly attenuated in the arterial media and adventitia at 3 days following injury in a dose-dependent manner.…”

Section: Studies Of Endovascular Irradiationmentioning

confidence: 99%

<b>Irradiation and Postangioplasty Restenosis</b>

et al. 2000

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SUMMARYOne of the most intriguing developments in recent years towards prevention of restenosis after angioplasty is the use of ionizing radiation. The background for the use of radiation treatment for this application is sound, since radiation is used not only to treat malignant cancerous growths but also is used for treatment of benign hyperplastic disorders such as post-surgical keloid formation and recurrence of pterygium after surgical removal. Restenosis can be considered a form of overexuberant wound healing triggered by angioplasty. Ionizing radiation inhibits serum-stimulated proliferation of many cell types including fibroblasts and smooth muscle cells in vitro and also suppresses the synthesis of collagen by cultured fibroblasts. Liermann who showed inhibition of post-stent restenosis first used ionizing radiation for restenosis prevention clinically in iliac and iliofemoral arteries. Subsequently, extensive animal studies in various restenosis models have shown a profound inhibitory effect of catheter-based radiation (endovascular brachytherapy) on neointima formation and overall vessel shrinkage (negative remodeling). 1) performed the first coronary balloon angioplasty. After more than 20 years, percutaneous transluminal coronary angioplasty (PTCA) is now widely accepted as an effective therapy for selected patients with symptomatic coronary artery disease. However, the over-compensatory wound healing response to angioplasty causing restenosis significantly limits the long-

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The Effect of Endovascular Irradiation on Platelet Recruitment at Sites of Balloon Angioplasty in Pig Coronary Arteries

Abstract: Endovascular irradiation at 15Gy or 30Gy after balloon angioplasty results in incomplete endothelial recovery, impaired resolution of intramural hemorrhage, and a dose-dependent increase in platelet recruitment at 1 month.

Cited by 49 publications

References 14 publications

Intracoronary β-Radiation Exacerbates Long-Term Neointima Formation in Balloon-Injured Pig Coronary Arteries

Intracoronary β-Radiation Exacerbates Long-Term Neointima Formation in Balloon-Injured Pig Coronary Arteries

High-Dose Intravascular β-Radiation After De Novo Stent Implantation Induces Coronary Artery Spasm

<b>Irradiation and Postangioplasty Restenosis</b>

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