Abstract | PURPOSE: To evaluate the efficacy of limited short-term systemic administration of rapamycin to prevent neointimal intimal hyperplasia (NIH) in a double-injury rat model of restenosis. METHODS: Aortic lesions were induced by perivascular placement of silicone cuffs around the aorta of 36 Lewis rats. After 3 weeks, the cuffs were removed, and the vessels were subjected to secondary balloon injury. Rapamycin ( sirolimus) was intravenously administered for 5 days in dosages of 0.5 or 2 mg/kg/d beginning at various time points relative to the balloon injury: (1) days -2 to +2, (2) days 1 to 5, or (3) days 7 to 11. For each treatment period, 6 rats received the 5-day course of the lower or higher dose of rapamycin. Eight rats served as controls undergoing 2-stage injury without rapamycin treatment. Morphometry and immunohistochemistry were performed at 21 days after angioplasty. RESULTS: NIH and intimal alpha-actin expression were inhibited by both dosages when treatment started 2 days before or 1 day after angioplasty. Results were statistically significant for the lower dose when started 1 day after angioplasty (p < 0.01) and for the higher dose when initiated 2 days before the intervention (p < 0.05). Treatment commencing at 7 days did not reduce NIH in either dosage group. CONCLUSIONS: In a double-injury rat model, NIH can be inhibited by short-term systemic rapamycin, but suppression of early cell migration and proliferation is pivotal. A limited peri-interventional antiproliferative therapy may be of value as an adjunct to control restenosis after balloon angioplasty and/or stenting.
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Authors | Thomas Jahnke, Fritz K W Schäfer, Hendrik Bolte, Gerrit Heuer, Ulf Karbe, Joachim Brossmann, Michael Brandt, Martin Heller, Stefan Müller-Hülsbeck |
Journal | Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists
(J Endovasc Ther)
Vol. 12
Issue 3
Pg. 332-42
(Jun 2005)
ISSN: 1526-6028 [Print] United States |
PMID | 15943508
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Actins
- Immunosuppressive Agents
- Sirolimus
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Topics |
- Actins
(metabolism)
- Angioplasty, Balloon
(adverse effects)
- Animals
- Aorta, Abdominal
(injuries, metabolism, pathology)
- Arterial Occlusive Diseases
(etiology, pathology, prevention & control)
- Cell Count
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Follow-Up Studies
- Hyperplasia
(pathology, prevention & control)
- Immunosuppressive Agents
(administration & dosage, therapeutic use)
- Male
- Muscle, Smooth, Vascular
(drug effects, metabolism, pathology)
- Rats
- Rats, Inbred Lew
- Secondary Prevention
- Sirolimus
(administration & dosage, therapeutic use)
- Time Factors
- Treatment Outcome
- Tunica Intima
(drug effects, metabolism, pathology)
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