LOCAL-DRUG DELIVERY WITH POROUS BALLOONS IN THE RABBIT - ASSESSMENT OF VASCULAR INJURY FOR AN IMPROVEMENT OF APPLICATION PARAMETERS

Objectives: Sufficient intramural drug concentrations with the use of porous balloon catheters can be achieved with additional vascular trau ma only, However, effective delivery of a potent drug even in deeper l ayers of the vessel wall might outweigh these traumatic side effects. Given the porous balloon catheter, the parameters of injection pressur e and applied fluid volume will influence the interventional result. M ethods: We tested a 2.5-mm porous balloon (35 75-mu m pores) in the ri ght carotid artery of New Zealand rabbits and used injection pressures of 1, 2, and 5 atm and fluid volumes of 2 and 4 mi of low-molecular-w eight heparin solution in combination with the different parameters (n = 5 animals/group). In 50 rabbits, an intimal fibromuscular plaque wa s induced by using the electrostimulation model. Balloon dilatation an d then application of the porous balloon was performed in 30 animals, 10 animals were only electrostimulated, and 10 animals served as a con trol group with balloon dilatation only, The vessels were excised 7 d after intervention, stained, and analyzed histomorpologically, Anti-Xa assays revealed the extent of systemically escaped drug, and serial c uts allowed for exact determination of vessel wall injuries, Results: Effective local drug delivery could not be achieved with an injection pressure of less than 2 atm. Specific pressure-driven effects such as jet injuries could be identified, When the pressure was high enough fo r disruptive drug delivery (greater than or equal to 2 atm), fluid vol umes of 4 mi led to loose elastic membranes and local thickening withi n the media, Conclusions: Sufficient intramural drug distribution usin g porous balloon catheters can be achieved with low injection pressure s. Different fluid volumes strongly determine the extent of additional vascular injury. (C) 1997 Wiley-Liss, Inc.