Endothelial seeding of angioplasty sites.

The major causes of mortality and morbidity complicating percutaneous transluminal angioplasty (PTA) are acute arterial re-occlusion and the development of chronic restenosis at the angioplasty site. These complications may affect PTA in 40-50% of cases, and their occurrence is directly attributable to loss of the endothelial cell monolayer during balloon dilatation. This study examined the hypothesis that acute and chronic occlusive complications following balloon angioplasty may be reduced by rapid restoration of the endothelial monolayer, achieved in turn by endothelial seeding. To define the optimum parameters for endothelial seeding of angioplasty sites, endothelial attachment to an in vitro model of vascular damage was quantified. Maximal endothelial adherence to damaged vascular surfaces was achieved with a seeding time of 30 min and a seeding density exceeding 3x10.;5 cells/cm2. Although initial endothelialadherence is a prime determinant of successful endothelial seeding, cell retention in arterial flow and maintenance of endothelial function are equally important. These parameters were investigated in vitro and the results suggested that native vascular surfaces provided an excellent substrate for endothelial seeding. Following on from the favourable results achieved during in vitro experiments, a method to transluminally seed experimental angioplasty sites was investigated in vivo. This method used a specially designed double balloon catheter to deliver and retain cultured endothelial cells at angioplasty sites. Using this technique initial endothelial adherence to dilated arterial segments was 49%, with 35% of the initially attached cells remaining attached after 100 min of arterial flow. Subsequent experiments revealed that transluminal endothelial seeding reduced acute platelet deposition following angioplasty, and in the longer term reduced both the degree of injury induced myointimal hyperplasia and the rate of arterial occlusion. Experimental endothelial seeding of angioplasty sites reduced acute and chronic complications after balloon dilatation and clearly has clinical potential as a therapeutic technique.