Histopathologic alterations after endovascular radiation and antiproliferative stents: similarities and differences.
BACKGROUND
Endovascular radiation and drug-eluting antiproliferative stents in experimental animals (normal pigs and rabbit arteries) show a decrease in the neointimal growth at 1 month vs. controls. However, this is accompanied by delayed healing characterized by persistence of neointimal fibrin (with or without inflammation), a decrease in smooth muscle cells, and incomplete endothelialization. Conversely, stainless steel control stents show complete healing with the neointima consisting of smooth muscle cells in a proteoglycan-collagen matrix and near complete luminal surface endothelialization.


RESULTS
Long-term (3 and 6 months) animal studies fail to show any benefit with radiation or drug-eluting stents. These experimental results are discrepant from those seen clinically in man where both therapies have shown benefit at 6 months, suggesting that animal data may not be predictive of clinical results. The main differences can be explained on the basis of preclinical studies performed in juvenile animals without underlying atherosclerosis, which leads to accelerated healing in animals vs. man such that 1 month animal data likely correspond to 6 months in man. Therefore long-term (24-30 months) angiographic and/or IVUS follow-up studies in man will be required to determine if drug-eluting stents will behave similarly to animal studies at 3 and 6 months.
Virmani
Renu
R
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, USA. virmani@afip.osd.mil
Farb
Andrew
A
Kolodgie
Frank D
FD
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D001918:Brachytherapy; D023903:Coronary Restenosis / Q000517:prevention & control*; D003331:Coronary Vessels / Q000473:pathology*; D005337:Fibrin / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007083:Iliac Artery / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D008855:Microscopy, Electron, Scanning; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010974:Platelet Aggregation; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D013193:Stainless Steel; D015607:Stents / Q000009:adverse effects; D013552:Swine; D013927:Thrombosis / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; D013193:Stainless Steel; D005337:Fibrin; D017239:Paclitaxel