FIBRIN GLUE CONTAINING FIBROBLAST GROWTH-FACTOR TYPE-1 AND HEPARIN WITH AUTOLOGOUS ENDOTHELIAL-CELLS REDUCES INTIMAL HYPERPLASIA IN A CANINE CAROTID-ARTERY BALLOON INJURY MODEL

Purpose: Intimal hyperplasia plagues all types of vascular interventio n. Early confluent reendothelialization may attenuate the smooth muscl e cell (SMC) proliferative response. We previously reported that fibro blast growth factor type 1 (FGF-1) and heparin at relative concentrati ons of 10 ng/ml:250 U/ml delivered in a fibrin glue (FG) suspension ca n selectively stimulate endothelial cells (EC) and inhibit SMC prolife ration in cell culture. This current study evaluates this surface trea tment with and without seeded autologous ECs on intimal hyperplasia in a canine carotid artery balloon injury model. Methods: Twenty-nine ad ult dogs underwent bilateral balloon injury to a 6 an segment of their carotid arteries. The injury resulted in a reproducible removal of th e intima and 4 to 6 medial lamellae. Nine dogs were used in part I to determine the percent retention of FGF-1 and EC when applied in a FG s uspension to the balloon-injured carotid arteries. Part 2 used the rem aining 20 dogs to determine the effect of this surface treatment on in timal hyperplasia. In 10 group I dogs, FG (fibrinogen 32.1 mg/ml and t hrombin 0.32 U/ml) containing FGF-1 (11 ng/ml) and heparin (250 U/ml) was applied to the luminal surface of one carotid artery,whereas the c ontralateral carotid artery underwent balloon injury alone. In 10 grou p TI dogs, an identical FG preparation with FGF-1 and heparin was appl ied to the surface of one carotid artery, whereas the contralateral ca rotid artery received FG/FGP-1/heparin that also contained autologous ECs (P3; 5 x 10(4) to 10 x 10(4) cells/cm(2)). Five dogs from both gro up I and group II were killed at 10 days and the remaining 10 dogs at 30 days. Histologic analysis and computerized morphometric analysis we re used to determine intimal and medial thickness and area, percent en dothelialization, and medial SMC proliferative rate. Results: There wa s no measurable neointima in any 10-day dog. There was no difference i n neointimal area between the treatments in group I 30-day dogs. There was a significant decrease in maximal neointimal area, intima/media t hickness ratio, and intima/media area ratio in group II 30-day dogs th at were treated with PG/FGF-1/heparin plus EC. There was an insignific ant increase in percent EC coverage and an insignificant decrease in m edial SMC proliferative rate in group II 10-day dogs treated with FG/E GF-1/heparin plus EC. Conclusions: In this canine carotid model, FG wi th FGF-1 and heparin did not induce significant intimal or medial thic kening after 10 or 30 days when compared with vessels that were only b alloon-injured. The seeding of autologous ECs within the FG/EGF-1/hepa rin suspension caused a reduction in neointima formation with no conco mitant medial thickening 30 days after injury. The use of FG to locall y deliver FGF-1 and ECs may have clinical relevance in the inhibition of intimal hyperplasia.