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 factor VII (rFVIIai) in a rabbit model of carotid artery thrombosis. Cyclic flow variations (CFVs), due to recurrent thrombus formation, were obtained in stenotic rabbit carotid arteries with endothelial injury. After 30 min of CFV, the animals received rFVIIai. If CFVs were abolished, animals were observed for 30 additional minutes, after which human recombinant activated factor VII was infused into the carotid artery to determine whether it could displace rFVIIai from tissue factor (TF), thus restoring CFV. An additional group of animals received rFVIIai to determine its duration of action. Recombinant FVIIai abolished CFVs in 8 of 9 rabbits (P < 0.01). This effect was reversible, as rFVIIa administration restored CFVs in all animals. A further study was initiated to assess whether TF-dependent reductions in coronary blood flow might contribute to the occurrence of myocardial injury during postischaemic reperfusion of rabbit hearts. Recombinant FVIIai resulted in significant reductions in both infarct size and no-reflow area, while rFVIIa produced a significant increase in both infarct size and no-reflow area. These data suggest that rFVIIai might be beneficial in patients with acute myocardial infarction undergoing reperfusion therapies.
Golino
P
P
Department of Internal Medicine, University of Naples Federico II, Italy. golino@unina.it
Ragni
M
M
Cirillo
P
P
D'Andrea
D
D
Ravera
M
M
Calabro
P
P
Ezban
M
M
Tommasini
P
P
Chiariello
M
M
D000818:Animals; D016893:Carotid Stenosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D015942:Factor VIIa / Q000008:administration & dosage*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D015942:Factor VIIa