Circulation, Vol 84, 1279-1288, Copyright © 1991 by American Heart Association
AV Kaplan, LL Leung, WH Leung, GW Grant, IR McDougall and TA Fischell
BACKGROUND. Platelet deposition at the site of injury caused by balloon
angioplasty is associated with acute closure and restenosis. METHODS AND
RESULTS. In a new ex vivo whole artery angioplasty model, we 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 +/- 2.2
x 10(6) platelets/cm2 were deposited at the site of balloon injury compared
with 0.7 +/- 0.2 x 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. CONCLUSIONS. 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. The 7E3 results suggest that approximately 70% of
platelet deposition at the site of balloon injury is GPIIb/IIIa dependent
and that the remaining 30% results from non-GPIIb/IIIa- mediated
platelet-subendothelial adhesion. Finally, the ex vivo whole artery system
is a useful model for studying platelet-vessel wall interactions under
physiologically defined parameters.
ARTICLES
Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model
Department of Medicine, Stanford University School of Medicine, Calif. 94305.
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