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J Am Coll Cardiol, 2002; 40:360-366
© 2002 by the American College of Cardiology Foundation
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EXPERIMENTAL STUDY

Effects of abciximab on the acute pathology of blood vessels after arterial stenting in nonhuman primates

Tullio Palmerini, MD*, Mark A. Nedelman, MS{dagger}, Lesley E. Scudder, BSc{ddagger}, Marian T. Nakada, PhD||, Robert E. Jordan, PhD||, Susan Smyth, MD, PhD{ddagger}, Ronald E. Gordon, PhD§, John T. Fallon, MD, PhD§ and Barry S. Coller, MD{ddagger},*

* Istituto di Cardiologia, Policlinico S. Orsola, University of Bologna, Bologna, Italy
{dagger} Primedica Corporation, Worcester, Massachusetts, USA
{ddagger} Medicine, New York, New York, USA
§ Pathology, Mount Sinai Medical School, New York, New York, USA
|| Centocor, Malvern, Pennsylvania, USA

Manuscript received September 18, 2001; revised manuscript received April 8, 2002, accepted April 18, 2002.

* Reprint requests and correspondence: Dr. Barry S. Coller, Head, Laboratory of Blood and Vascular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
collerb{at}rockefeller.edu

OBJECTIVES: This study was designed to assess the effect of abciximab on platelet and leukocyte deposition 60 min after stent insertion in nonhuman primates.

BACKGROUND: Although it is well established that abciximab improves both short- and long-term clinical outcomes after stent placement, there have been no studies assessing its effect on early platelet and leukocyte deposition.

METHODS: Cynomolgus monkeys were pretreated with aspirin and either saline or a 0.4 mg/kg bolus of abciximab, and then subjected to angioplasty and Palmaz-Schatz stent placement in the common iliac artery or abdominal aorta. After 60 min, animals were euthanized and the stented artery was evaluated by immunohistochemistry and morphometry.

RESULTS: Complete occlusion of the stented vessel with a thin fibrin(ogen) meshwork and trapped blood occurred in two saline-treated and two abciximab-treated animals. In the four remaining saline-treated animals, a layer of erythrocytes trapped in a network of fibrin(ogen) was noted close to the vessel wall, and this was covered by a layer of large, irregular platelet thrombi. Leukocytes formed a monolayer on top of the platelets and near stent struts. In the four remaining abciximab-treated animals, the mean erythrocyte area was 65% smaller (p = 0.070), the platelet aggregate area was 89% smaller (p = 0.049) and the luminal area was 59% larger (p = 0.004). A monolayer of leukocytes also formed on top of the platelets and near stent struts.

CONCLUSIONS: In control stented blood vessels in this study, platelet thrombi formed not at the vessel wall, but on top of an erythrocyte-rich layer, and platelets recruited leukocytes. Abciximab decreased the size of platelet thrombi, but did not prevent leukocyte recruitment.

Abbreviations and Acronyms
  GP
  glycoprotein
  IEL
  internal elastic lamina
  PAI-1
  plasminogen activating inhibitor-1
  PBS
  phosphate-buffered saline
  PSGL-1
  P-selectin glycoprotein ligand-1
  RPFA
  rapid platelet function assay
  TF
  tissue factor
  t-PA
  tissue plasminogen activator




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