QUANTITATIVE-EVALUATION OF LOCAL-DRUG DELIVERY USING THE INFUSASLEEVECATHETER

Background: Restenosis is the most common long-term complication after angioplasty. Local delivery of pharmacologic agents at the site of an gioplasty holds promise as a means of achieving higher concentrations of drug in the arterial wall than can be obtained by systemic infusion . In this study, a novel local drug delivery catheter system, the Infu saSleeve(TM) catheter, was evaluated in a porcine coronary balloon inj ury model. The purpose of the study was to evaluate the efficacy of so lute transfer to the arterial wall and the influence of varying suppor ting angioplasty balloon pressure. Methods and Results: Ten pigs (tota l of 22 arterial segments) underwent overstretch balloon injury (arter y/balloon ratio 1:1.29) with a standard angioplasty balloon, In 7 anim als (16 arterial segments) horseradish peroxidase(HRP; 10 mg/ml) was a dministered locally after injury, by tracking the local infusion cathe ter as a sheath over the angioplasty balloon to the intended site of a rterial drug delivery, Supporting angioplasty balloons were inflated t o one of the three different pressures. In 3 pigs HRP (10 mg/ml) was a dministered intravenously. No significant arterial injury caused by th e local delivery device was evident on histological examination (disru ption of the internal lamina elastica, arterial media, or thrombosis). Radial concentrations of the HRP reaction product in the first 150 mu m of the arterial wall were quantified against known standards by mea surement of light transmission through tissue sections. Mean HRP conce ntrations were not significantly different from those obtained by intr avenous infusion using a supporting pressure of 1 atm or a supporting pressure of 3 atm of the underlying angioplasty balloon. However, a su pporting pressure of 6 atm resulted in a 6-fold greater mean HRP conce ntration in the arterial wall than that which could be achieved by sys temic administration of an equal volume of tracer (P < 0.001). Conclus ion: Thus solute can be delivered throughout the coronary media by the InfusaSleeve, with the magnitude of wall uptake related to support pr essure. Local delivery at 6 atm support pressure produced substantiall y greater uptake than did systemic delivery. (C) 1997 Wiley-Liss, Inc.