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Myointimal hyperplasia (MIH) after vascular intervention is a major problem. Recent reports describing elimination of within-stent restenosis by means of rapamycin-eluting stents prompted us to examine the effect of systemic oral rapamycin on MIH induced by arterial trauma. We studied the effect of oral rapamycin on MIH after rabbit aorta balloon injury. Thirty-five New Zealand white rabbits (2.5-3 kg) had aortic injury and were given either no rapamycin (control), 0.1 (low dose) rapamycin mg/kg/day, or 0.4 mg/kg/day (high dose). Rapamycin was started 1 week before injury and continued for 3 (4 weeks total) or 6 weeks (7 weeks total) post-injury. Sections were analyzed to measure aortic intima/media area ratios (I:M) at either 3 or 6 weeks. At 3 weeks, the I:M (mean +/- SD) for controls was 0.53 +/- 0.1; for low dose, 0.17 +/- 0.13; and for high dose, 0.24 +/- 0.07 (p < 0.001 vs. control). At 6 weeks, the I:M for controls was 0.52 +/- 0.12; for low dose-4 weeks, 0.29 +/- 0.15; low dose-7 weeks, 0.33 +/- 0.07; and high dose-4 weeks, 0.47 +/- 0.16. At 6 weeks only the difference between the low dose-4 weeks and control I:M ratios was significant (p = 0.018). The results confirm earlier studies showing that systemic rapamycin inhibits MIH after arterial injury when drug therapy is started before injury. Therapy for 3 or 6 weeks after injury yields similar inhibition, indicating that exposure to the drug early in the response to injury is more important than prolonged exposure. We observed a paradoxical relation between dose and degree of MIH inhibition, with the low dose being more effective than the high dose at both time intervals studied. Overall, the results suggest that oral rapamycin therapy might be a useful adjunct to clinical interventions at risk for development of MIH.

Our objective was to evaluate restenosis after stenting of femoropopliteal occlusions and the impact of percutaneous transluminal angioplasty (PTA) on recurrent stenosis. We used a retrospective analysis of contrast angiograms obtained during follow-up of stented limbs. Subjects included 27 claudicants (34 limbs) who had complete superficial femoral artery occlusion treated with PTA and Wallstents at the Veterans Adminstration Medical Center. During follow-up, 31 PTAs, three thrombolytic treatments, and one additional stenting were performed. Outcome was measured by contrast angiography. Primary patency at 1 and 3 years was 38% and 8% after stenting, and secondary patency (PTA required at least once in 21/34 limbs) was 89% and 55%, respectively. PTA performed during follow-up reduced within-stent restenosis on average from 48.3 ± 13.6% to 22.8 ± 18.0%. Recurrent stenosis after PTA measured 14.9 ± 10.9 months later was 46.8 ± 16.7%, showing little permanent impact of PTA on stenosis. Severe within-stent stenosis develops commonly after initial stenting of complete femoropopliteal occlusions. Supplemental PTA performed during follow-up provides immediate improvement in lumen diameter, but severe restenosis is still likely to recur. [ABSTRACT FROM AUTHOR]