Flavone-8-acetic acid (Flavonoid) profoundly reduces platelet-dependent thrombosis and vasoconstriction after deep arterial injury In vivo.
BACKGROUND
Flavone-8-acetic acid (FAA; [Flavonoid]), an adjuvant antitumor drug, inhibits ristocetin-induced aggregation of human platelets. The effect of FAA on platelet-dependent thrombosis was studied in vivo in the porcine carotid artery after deep arterial injury by balloon angioplasty.


RESULTS
(111)In-labeled autologous platelet and (125)I-labeled porcine fibrin(ogen) deposition, and the incidence of macroscopic mural thrombosis onto deeply injured artery (tunica media) were compared in 20 pigs (40+/-1 kg [mean+/-SEM], body surface area=1.0+/-0.1 m(2)), randomized to FAA bolus (n=10) of 5.5g/m(2), followed by an infusion at 0.14g. m(-2). min(-1) or placebo (n=10). Vasoconstriction was measured immediately beyond the dilated segment using quantitative angiography. Platelet deposition (x10(6)/cm(2) of carotid artery) was reduced over 12-fold in pigs treated with FAA (13+/-3 versus 164+/-51, P=0.001) compared with placebo. Fibrin(ogen) deposition (x10(12) molecules/cm(2) of carotid artery) did not significantly differ in FAA-treated pigs versus placebo (40+/-8 versus 140+/-69, P=0.08). Large mural thrombi were present in 100% of placebo-treated pigs versus very small thrombi in 40% of FAA-treated pigs (P=0.005). Vasoconstriction was reduced from 46+/-6% in the placebo group to 15+/-3% in the FAA group (P<0.001). Plasma level of FAA before angioplasty was 515+/-23 microgram/mL. The activated partial thromboplastin time was unchanged. The bleeding time was >2SD above the normal mean in 4 of 5 treated pigs (increased from 157+/-29 to 522+/-123 s).


CONCLUSIONS
FAA markedly reduced platelet deposition, mural thrombi, and injury-induced vasoconstriction after deep arterial injury, suggesting that a major inhibition of platelet glycoprotein Ibalpha may be beneficial therapy.
Mruk
J S
JS
Buchanan County Cardiology, PC, St. Joseph, Missouri, USA.
Webster
M W
MW
Heras
M
M
Reid
J M
JM
Grill
D E
DE
Chesebro
J H
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D002404:Catheterization; D005419:Flavonoids / Q000493:pharmacokinetics / Q000494:pharmacology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors; D013552:Swine; D013927:Thrombosis / Q000188:drug therapy*; D014661:Vasoconstriction / Q000187:drug effects*
D000970:Antineoplastic Agents; D005419:Flavonoids; D019038:Platelet Glycoprotein GPIb-IX Complex; C049328:flavone acetic acid