Introduction
Thrombosis is commonly associated with arterial injury. Clinically, this is seen with all interventional procedures designed to treat coronary artery stenosis, such as percutaneous transluminal coronary angioplasty (PTCA),1 directional coronary, 1 atherectomy (DCA)2 and coronary artery stenting.3 Acute thrombosis occasionally results in total occlusion of the vessel lumen. However, more typical is the deposition of smaller nonocclusive mural thrombi.
Thrombosis is also a common feature of many animal models of arterial injury.4-8 These models have provided considerable information about the molecular events associated with injury-induced thrombus formation. Platelet adherence to the injured arterial wall occurs within minutes in all models of arterial injury. In some models, platelet deposition is followed by fibrin deposition, a consequence of activation of the coagulation cascade. The presence and extent of fibrin deposition varies with the degree of injury (superficial or deep), the type of vessel (carotid, femoral, aorta, or coronary), the state of the vessel prior to injury (normal, cholesterol fed, previously injured), and the species. In the pig carotid balloon injury model, endothelial denudation in the absence of medial injury is associated with platelet deposition but no fibrin generation. More severe injury, defined by the presence of a medial tear, results in marked platelet accumulation and fibrin generation, even in the presence of high doses of heparin.4,9 Unlike the porcine model, balloon injury to normal rodent arteries is associated with rapid platelet deposition but does not result in significant fibrin deposition, even in the presence of medial injury.5-8
In contrast to that found using normal arteries, fibrin deposition is seen when previously injured rabbit arteries, possessing a neointima, are subjected to a second injury.5,7,8,10 As determined by scanning and transmission electron microscopy, abundant fibrin formation is detected within 30 minutes of the reinjury. Platelet deposition is also more dense after the second injury and associated with fibrin-platelet microthrombi. We have recently found a similar difference between single and double injury in rat aorta and carotid arteries. These studies suggest that, in contrast to the deposition of platelets, which accompanies any injury to the arterial wall, the deposition of fibrin and the formation of large thrombi are more dependent on the type of injury produced and may be regulated by specific processes occurring in the arterial wall.
