Effects of recombinant active site-blocked activated factor VII in rabbit models of carotid stenosis and myocardial infarction

We tested the effects of human recombinant active site-blocked activated fa ctor VII (rFVIIai) in a rabbit model of carotid artery thrombosis. Cyclic f low variations (CFVs), due to recurrent thrombus formation, were obtained i n stenotic rabbit carotid arteries with endothelial injury. After 30 min of CFV, the animals received rFVIIai. If CFVs were abolished, animals were ob served for 30 additional minutes, after which human recombinant activated f actor VII was infused into the carotid artery to determine whether it could displace rFVIIai from tissue factor (TF), thus restoring CFV. An additiona l group of animals received rFVIIai to determine its duration of action. Re combinant FVIIai abolished CFVs in 8 of 9 rabbits (P < 0.01), This effect w as reversible, as rFVIIa administration restored CFVs in all animals. A fur ther study was initiated to assess whether TF-dependent reductions in coron ary blood flow might contribute to the occurrence of myocardial injury duri ng postischaemic reperfusion of rabbit hearts, Recombinant FVIIai resulted in significant reductions in both infarct size and no-reflow area, while rF VIIa produced a significant increase in both infarct size and no-reflow are a. These data suggest that rFVIIai might be beneficial in patients with acu te myocardial infarction undergoing reperfusion therapies. Blood Coagal Fib rinolysis 11 (suppl 1):S149-S158 (C) 2000 Lippincott Williams & Wilkins.