Flavone-8-acetic acid (Flavonoid) profoundly reduces platelet-dependent thrombosis and vasoconstriction after deep arterial injury in vivo

Jozef S. Mruk, Mark W I Webster, Magda Heras, Joel M Reid, Diane E. Grill, James H. Chesebro

Research output: Contribution to journalArticle

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Abstract

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 Ibα may be beneficial therapy.

Original languageEnglish (US)
Pages (from-to)324-328
Number of pages5
JournalCirculation
Volume101
Issue number3
StatePublished - Jan 25 2000

Fingerprint

flavone acetic acid
Vasoconstriction
Flavonoids
Thrombosis
Swine
Blood Platelets
Wounds and Injuries
Placebos
Carotid Arteries
Fibrin
Platelet Glycoprotein GPIb-IX Complex
Ristocetin
Tunica Media
Platelet Membrane Glycoproteins
Balloon Angioplasty
Body Surface Area
Platelet Aggregation
Antineoplastic Agents
Angiography

Keywords

  • Angioplasty
  • Platelet aggregation inhibitors
  • Platelets
  • Thrombus
  • Vasoconstriction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Flavone-8-acetic acid (Flavonoid) profoundly reduces platelet-dependent thrombosis and vasoconstriction after deep arterial injury in vivo. / Mruk, Jozef S.; Webster, Mark W I; Heras, Magda; Reid, Joel M; Grill, Diane E.; Chesebro, James H.

In: Circulation, Vol. 101, No. 3, 25.01.2000, p. 324-328.

Research output: Contribution to journalArticle

Mruk, Jozef S. ; Webster, Mark W I ; Heras, Magda ; Reid, Joel M ; Grill, Diane E. ; Chesebro, James H. / Flavone-8-acetic acid (Flavonoid) profoundly reduces platelet-dependent thrombosis and vasoconstriction after deep arterial injury in vivo. In: Circulation. 2000 ; Vol. 101, No. 3. pp. 324-328.
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T1 - Flavone-8-acetic acid (Flavonoid) profoundly reduces platelet-dependent thrombosis and vasoconstriction after deep arterial injury in vivo

AU - Mruk, Jozef S.

AU - Webster, Mark W I

AU - Heras, Magda

AU - Reid, Joel M

AU - Grill, Diane E.

AU - Chesebro, James H.

PY - 2000/1/25

Y1 - 2000/1/25

N2 - 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 Ibα may be beneficial therapy.

AB - 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 Ibα may be beneficial therapy.

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KW - Platelet aggregation inhibitors

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