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(Circulation. 2000;101:324.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Flavone-8-Acetic Acid (Flavonoid) Profoundly Reduces Platelet-Dependent Thrombosis and Vasoconstriction After Deep Arterial Injury In Vivo

Jozef S. Mruk, MD, PhD; Mark W. I. Webster, MB, ChB; Magda Heras, MD; Joel M. Reid, PhD; Diane E. Grill, MS; James H. Chesebro, MD

From Buchanan County Cardiology, PC (J.S.M.), St. Joseph, Mo; Green Lane Hospital (M.W.I.W.), Epsom, Auckland, New Zealand; Hospital Clinic I Provincial de Barcelona (M.H.), Spain; Department of Oncology and Comprehensive Cancer Center (J.M.R.), and Department of Biostatistics (D.E.G.), Mayo Clinic and Mayo Foundation, Rochester, Minn; and Cardiovascular Institute (J.H.C.), Mount Sinai Medical Center, New York.

Correspondence to James H. Chesebro, MD, Cardiovascular Institute, Box 1030, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029-6574.

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.

Methods and Results—¹¹¹In-labeled autologous platelet and ¹²⁵I-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 m²), randomized to FAA bolus (n=10) of 5.5g/m², 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 (x10⁶/cm² 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 (x10¹² molecules/cm² 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 µg/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 Ib may be beneficial therapy.

Key Words: angioplasty • platelets • platelet aggregation inhibitors • thrombus • vasoconstriction

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				S. Goto and S. Handa Antithrombotic Effects of Flavonoid Circulation, January 30, 2001; 103 (4): e23 - e23. [Full Text] [PDF]