THE EFFECT OF POROUS INFUSION BALLOON DELIVERED ANGIOPEPTIN ON MYOINTIMAL HYPERPLASIA AFTER BALLOON INJURY IN THE RABBIT

Background. Angiopeptin, a synthetic somatostatin analogne, reduces my ointimal hyperplasia after experimental balloon angioplasty when given subcutaneously. The feasibility and efficacy of a single dose of angi opeptin delivered locally via the Wolinsky porous balloon on myointima l hyperplasia were studied. Methods and Results. Three rabbits receive d I-125-angiopeptin in the mid abdominal aorta via the Wolinsky balloo n at 5 atm for 1 minute after balloon injury. Thirty minutes later, au toradiography demonstrated radioactivity in the media and the adventit ia. Forty rabbits were divided equally into one control group receivin g saline and three angiopeptin groups receiving 1, 10, or 100 mug/mL o f angiopeptin delivered locally at 5 atm for 1 minute via the Wolinsky balloon into the mid abdominal aorta after balloon injury of the enti re abdominal aorta. On day 21, the abdominal aortas were fixed in situ and harvested. There was no statistical difference in the amount of m yointimal hyperplasia in the locally treated aorta in the angiopeptin groups compared with the control group. However, in the lower abdomina l aorta, where balloon injury without local delivery was performed, th ere was a significant reduction of myointimal hyperplasia in the highe st-concentration angiopeptin group (P<.001 versus the control group). Electron microscopy showed that the control animals had a pseudointima of smooth muscle cells throughout the aorta, whereas in all the angio peptin-treated animals, endothelial cells were present at both locatio ns. Conclusions. Angiopeptin can be delivered intramurally via the Wol insky porous balloon and reduces myointimal hyperplasia only in the ar ea distal to the local drug delivery site (downstream effect), possibl y by heating the injured endothelium, by transport via the vasa vasora , and/or by systemic effect.