FIBRIN-RICH AND PLATELET-RICH THROMBUS FORMATION ON NEOINTIMA - RECOMBINANT TISSUE FACTOR PATHWAY INHIBITOR PREVENTS FIBRIN FORMATION AND NEOINTIMAL DEVELOPMENT FOLLOWING REPEATED BALLOON INJURY OF RABBIT AORTA

Thrombus formation and neointimal growth are the critical events in re stenosis after balloon angioplasty. However, the responses of diseased vessels to injuries caused by balloon angioplasty have not been well examined. We investigated the thrombus formation and neointimal develo pment following the balloon injury to the previously induced neointima in the rabbit aorta and the effects of recombinant tissue factor path way inhibitor (rTFPI) on these responses. Rabbit thoracic aortas were subjected to injury with a Fogarty 4F balloon catheter at 1.75 atm (fi rst injury), and 4 weeks later the same vessels were subjected iu the second injury with a Swan-Ganz 5F balloon catheter at 1.4 arm (mild-in jury group) or 1.8 atm (severe-injury group), and immediately after th at a retrograde bolus injection of rTFPI (100 mu g/kg body weight) or saline was performed into the injured segments via the central tube of the Swan-Ganz catheter. Twenty minutes after the second injury, the i njured surfaces were covered with platelet-rich thrombi in the mild-in jury group and with fibrin-rich thrombi in the severe-injury group. Da maged intimal smooth muscle cells, which were immunohistochemically po sitive for tissue factor (TF), were observed beneath the fibrin rich t hrombi. The neointima 4 weeks after the second injury was significantl y thicker in the severe-injury group than in the mild-injury group. Th e bolus infusion of rTFPI markedly inhibited fibrin formation on the i njured surfaces, and significantly reduced the neointimal development in the severe-injury group at 4 weeks after the second injury. These r esults indicate that TF-dependent coagulation pathway is primarily res ponsible for fibrin-rich thrombus formation and may play an important role in neointimal development following the balloon injury to the rab bit aortic neointima. Additionally the bolus administration of rTFPI t o the injured vessels could prevent mural thrombus formation and neoin timal growth after balloon angioplasty.