Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model

Journal Article · Sun Sep 01 04:00:00 EDT 1991 · Circulation; (United States)

DOI:https://doi.org/10.1161/01.CIR.84.3.1279· OSTI ID:5028580

Kaplan, A V; Leung, L L; Leung, W H; Grant, G W; McDougall, I R; Fischell, T A ^[1]

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1. Department of Medicine, Stanford University School of Medicine, CA (United States)

Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis. In a new ex vivo whole artery angioplasty model, the authors examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 {plus minus} 2.2 {times} 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 {plus minus} 0.2 {times} 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin. At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation.

• OSTI ID: 5028580
• Journal Information: Circulation; (United States), Journal Name: Circulation; (United States) Vol. 84:3; ISSN 0009-7322; ISSN CIRCA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMAL TISSUES
ANIMALS
ANTIBODIES
ANTICOAGULANTS
AORTA
ARTERIES
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION
BLOOD COAGULATION FACTORS
BLOOD PLATELETS
BLOOD VESSELS
BODY
BODY FLUIDS
CARBOHYDRATES
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
COAGULANTS
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELECTRON MICROSCOPY
ENZYMES
GLYCOPROTEINS
HEMATOLOGIC AGENTS
HEMOSTATICS
HEPARIN
HYDROLASES
IN VITRO
INDIUM 111
INDIUM ISOTOPES
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MATERIALS
MEDICINE
MICROSCOPY
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
MUCOPOLYSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PERFUSED TISSUES
POLYSACCHARIDES
PROTEINS
RABBITS
RADIOISOTOPES
SACCHARIDES
SCANNING ELECTRON MICROSCOPY
SERINE PROTEINASES
SURGERY
THROMBIN
THROMBOSIS
TISSUES
VASCULAR DISEASES
VERTEBRATES