INTRAMURAL DELIVERY OF AGENT VIA A DRUG-DELIVERY SLEEVE - HISTOLOGICAL AND FUNCTIONAL-EVALUATION

Background The infusion sleeve is a novel drug-delivery catheter syste m designed to deliver an agent under controlled conditions into the ar terial wall at the site of angioplasty. The purpose of the present stu dy was to characterize the delivery agent via the infusion sleeve in e x vivo and in vivo models. Methods and Results The delivery of horsera dish peroxidase via the infusion sleeve was studied in a porcine expla nted heart model. Under physiological conditions, arteries underwent b alloon injury (approximate to 10% overstretch), after which horseradis h peroxidase (2.5 mL) was delivered at specific pressures. Cross-secti onal analysis demonstrated greater staining when the agent was deliver ed at increasing pressures. The infusion sleeve was evaluated in an in vivo canine coronary model. With an infusion sleeve loaded over a sta ndard dilatation catheter through a 9F guide, overstretch balloon inju ry was performed, after which fluoresceinated heparin was delivered. A nimals were killed 2 hours after delivery. Fluoresceinated heparin-tre ated segments demonstrated high fluorescence signals, localizing with smooth muscle cell nuclei with less activity in the interstitium. The functional significance of intramural heparin delivery was studied in a porcine carotid model. In the presence of In-111-labeled platelets, arteries underwent overstretch injury followed by delivery of heparin (50 or 100 units/kg) or vehicle. Platelet deposition was reduced at 30 minutes (57%, P<.01) and 12 hours (39%, P=.06) compared with saline c ontrols. Conclusions Agent delivery via the infusion sleeve is pressur e dependent. transmural delivery is possible with minimal disruption o f arterial wall architecture; the infusion sleeve is compatible with s tandard angioplasty equipment; and heparin delivery at the site of bal loon injury significantly reduces platelet deposition in a porcine mod el for a minimum of 12 hours.