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Thromb Haemost 1996; 76(05): 799-806
DOI: 10.1055/s-0038-1650663
Original Article
Schattauer GmbH Stuttgart

Inhibitory Effect of a Novel Orally Active GP IIb/IIIa Inhibitor, SC-54684A on Intimal Thickening in the Guinea Pig Femoral Artery

Kazuo Umemura
The Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
,
Hiroshi Nishiyama
The Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
,
Shinji Kikuchi
The Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
,
Kazunao Kondo
The Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
,
Mitsuyoshi Nakashima
The Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan
› Author Affiliations
Further Information

Publication History

Received 11 September 1995

Accepted after resubmission 25 July 1996

Publication Date:
11 July 2018 (online)

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Summary

The inhibitory effect of a novel orally active platelet membrane glycoprotein receptor complex IIb/IIIa (GP IIb/IIIa) inhibitor, SC-54684A is studied on intimal thickening in the guinea pig femoral artery. A segment of the femoral artery was occluded by a platelet-rich thrombus induced by photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after successful thrombolysis by tissue-type plasminogen activator, intimal thickening occurred at the irradiated site. SC-54684A (30 mg/kg), administered 2 h before photochemical reaction, significantly (P <0.05) prolonged the time to occlusion of the femoral artery; in this respect aspirin (100 mg/kg) was ineffective. A combination of SC-54684A and recombinant tissue-type plasminogen activator (rt-PA) increased the frequency of reopening and significantly (P <0.05) prolonged the duration of reflow compared with rt-PA alone. Further, SC-54684A administered orally twice a day for 3 weeks significantly (P <0.05) inhibited intimal thickening but aspirin, administered orally once a day for 3 weeks, was ineffective. Scanning electron microscopy revealed extensive platelet adhesion and aggregation on the denuded vessel walls in the untreated group 24 h after successful thrombolysis. In separate experiments, SC-54684A markedly inhibited platelet aggregation ex-vivo. Inhibition of platelet adhesion and aggregation at the site of endothelial injury by SC-54684A (via GPIIb/IIIa inhibition) may account for its inhibitory effect on intimal thickening

 

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