What is the clinical evidence from this study?

Study design: Other. Population: Intimal hyperplasia after carotid balloon injury (n=48). Intervention: Rapamycin, imatinib mesilate, or cysteamine vs. Control. Primary outcome: Intimal area at 2 weeks (rapamycin group) (p=0.016).

January 1, 2013Open Access

Inhibition of intimal hyperplasia by local perivascular application of rapamycin and imatinib mesilate after carotid balloon injury

Key Result

Perivascular application of rapamycin significantly reduced the intimal area compared to control at 2 weeks after carotid injury (0.06 vs 0.2 mm2, P=0.016).

Structured PICO

Does perivascular application of rapamycin, imatinib mesylate, or cysteamine reduce intimal hyperplasia in a rat carotid balloon injury model?

Population

48 male Sprague-Dawley rats underwent carotid balloon injury and were treated with perivascular drugs to assess intimal hyperplasia over 2 to 4 weeks.

Intervention

Topical perivascular application of rapamycin (1 mg/kg), imatinib mesylate (10 mg/kg), or cysteamine (60 mg/kg) mixed with 40% pluronic gel solution over the injured carotid artery.

Comparator

Control group receiving carotid injury without active drug application.

Outcome

Intimal area and intima-to-media (I/M) ratio at 2 and 4 weeks after injury.surrogate

Perivascular delivery of rapamycin or imatinib mesylate using pluronic gel effectively attenuates intimal hyperplasia following carotid balloon injury in rats without causing medial thinning.

Main Result

Absolute Event Rate: 0.06% vs 0.2%

p-value: p=0.016

Limitations

The duration of effective drug delivery by the perivascular gel is not defined.
The local tissue concentrations of the drugs were not investigated due to technical difficulties.
The submaximal dose of perivascular delivery was not defined.

Abstract

PURPOSE: Inhibition of the intimal hyperplasia after vascular surgery is an important issue. The purpose of this study is to define whether perivascular application of rapamycin, imatinib mesylate or cysteamine can reduce intimal hyperplasia in a carotid balloon injury model. METHODS: Each drug was mixed with 40% pluronic gel solution and was topically applied over the injured carotid artery evenly. Two or four weeks after injury, the arteries were harvested and morphometric analysis was done. RESULTS: The medial areas were not significantly different in each group and a thinning of the media as a toxic drug effect was not observed in any treatment group. The intimal area and intima-to-media (I/M) ratio were significantly reduced in rapamycin-treated group and imatinib-treated group (P < 0.05). But cysteamine-treated group showed a trend of decrease in I/M ratio in 2 weeks, but no difference in 4 weeks. CONCLUSION: Perivascular delivery of imatinib or rapamycin with pluronic gel attenuated the development of intimal hyperplasia. But cysteamine did not. Further studies are needed to refine the optimal drug dosages in large animal models.

Ask AI

Helpful

Bookmark

View Full Paper