Pathology of radiation-induced coronary artery disease in human and pig.
OBJECTIVE
External beam mediastinal radiation-induced accelerated coronary atherosclerotic heart disease in humans has been recognized, especially when the condition occurs in young persons. The purpose of the present study was to compare external beam radiation-induced accelerated coronary atherosclerosis in humans with that seen in the pig coronary arteries following radioactive stent placement.


METHODS
A literature review of radiation-induced coronary artery disease was performed. In addition, clinical records and coronary histology from the Armed Forces Institute of Pathology Registry were reviewed from patients who had received external beam radiation for mediastinal malignancies. Coronary arteries from pigs that had radioactive coronary stent placement were evaluated from our stent pathology laboratory and analyzed for comparison with the human disease.


RESULTS
In humans, the characteristics of the intimal plaque in accelerated atherosclerosis postradiation therapy were similar to that seen in typical atherosclerotic coronary disease in the absence of radiation therapy. However, medial thinning and adventitial fibrosis were the distinguishing pathologic arterial changes secondary to radiation seen in humans. Radioactive stent placement in pig coronary arteries produced similar changes to that observed in humans post-external beam radiation, consisting of medial injury and adventitial thickening accompanied by intimal foam cell collections, calcification, and necrotic core formation containing cholesterol clefts resulting in severe luminal narrowing.


CONCLUSIONS
Radiation, delivered via external beam or radioactive stent, induces changes of intimal atherosclerosis with medial thinning and adventitial scarring in human and pig. Therefore, pending completion of long-term clinical studies, caution should be exercised before the widespread use of brachytherapy is advocated for the treatment and prevention of coronary restenosis.
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA. virmani@afip.osd.mil
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Virmani
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Farb
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Carter
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Jones
D000818:Animals; D001918:Brachytherapy / Q000009:adverse effects; D003327:Coronary Disease / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008479:Mediastinal Neoplasms / Q000532:radiotherapy; D011832:Radiation Injuries / Q000209:etiology* / Q000473:pathology*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000473:pathology; D015607:Stents; D013552:Swine