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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, Lesley E. Scudder, BSc, Marian T. Nakada, PhD^||, Robert E. Jordan, PhD^||, Susan Smyth, MD, PhD, Ronald E. Gordon, PhD, John T. Fallon, MD, PhD and Barry S. Coller, MD^,*

^* Istituto di Cardiologia, Policlinico S. Orsola, University of Bologna, Bologna, Italy
Primedica Corporation, Worcester, Massachusetts, USA
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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