Active-site inactivated FVIIa decreases thrombosis and necrosis in a random skin flap model of acute ischemia.
BACKGROUND
Previous studies have emphasized the role of ischemia in inducing vascular thrombosis.


METHODS
Using a skin flap model of acute ischemia in the rat, we studied the effect of active-site inactivated factor VIIa (FVIIai), an inhibitor of tissue factor (TF), on tissue survival during acute ischemia.


RESULTS
Ribonuclease protection analysis revealed an increase in TF in ischemic parts of the flap, and in situ hybridization localized this increase mainly to perivascular cells. A decrease in vascular thrombosis, as determined by fibrin immunostaining, was observed in FVIIai-treated animals. Intravenous administration of FVIIai had a positive impact on survival of the flap. Laser Doppler flowmetry revealed an increase in blood flow in the FVIIai-treated group. In treated animals, prothrombin time (PT) was increased (P < 0.01), whereas partial thromboplastin time (APTT) was unaltered; no significant impairment in systemic hemostasis (peri- and postoperative bleeding) was observed.


CONCLUSIONS
These findings demonstrate that TF expression is increased in perivascular cells in ischemic skin flaps and that FVIIai, by inhibiting TF, increases flap survival.
Alizadeh
Navid
N
Plastic and Reconstructive Surgery Unit, Geneva University Hospital, Geneva, Switzerland.
Pittet
Brigitte
B
Tenorio
Xavier
X
Pyke
Charles
C
Baetens
Danielle
D
Schlaudraff
Kai-Uwe
KU
Montandon
Denys
D
Ezban
Mirella
M
Pepper
Michael S
MS
D000208:Acute Disease; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D015942:Factor VIIa / Q000494:pharmacology; D005260:Female; D007511:Ischemia / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D013524:Surgical Flaps / Q000473:pathology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology / Q000473:pathology*; D013997:Time Factors; D014022:Tissue Survival / Q000187:drug effects
D013925:Thromboplastin; D015942:Factor VIIa