Jahnke Thomas, Schäfer Fritz K W, Bolte Hendrik, Heuer Gerrit, Karbe Ulf, Brossmann Joachim, Brandt Michael, Heller Martin, Müller-Hülsbeck Stefan
Department of Diagnostic Radiology, University Clinics Schleswig-Holstein (UKSH), Campus Kiel, Germany.
J Endovasc Ther. 2005 Jun;12(3):332-42. doi: 10.1583/04-1498R.1.
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.
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.
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.
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.
