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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1271.)
© 2009 American Heart Association, Inc.

National Cholesterol Awareness Month

Inhibition of Platelet-Rich Arterial Thrombus In Vivo

Acute Antithrombotic Effect of Intravenous HMG-CoA Reductase Therapy

Chike Obi; Waldemar Wysokinski; Krzystof Karnicki; Whyte G. Owen; Robert D. McBane, II

From the University of Pittsburgh School of Medicine, Pittsburgh, Penn. (C.O), Division of Cardiology (W.W., K.K., R.D.M.) and the Section of Hematology (W.W., W.G.O., R.D.M.) Research Mayo Clinic, Rochester, Minn.

Correspondence to Robert D. McBane II, Division of Cardiovascular Medicine, Mayo Clinic, 200 First Street, Rochester, MN 55905. E-mail mcbane.robert{at}mayo.edu

Abstract

Objective— To test the hypothesis that statins will acutely inhibit platelet thrombus formation, intravenous lovastatin was assessed in our well-characterized porcine carotid injury model.

Methods and Results— The first carotid artery was crush-injured and harvested after 30 minutes. Pigs then received intravenous lovastatin (100 µg/kg bolus+100 µg/kg/h infusion, n=6) or saline (n=11) before injury of the second carotid artery. Thrombus size was quantified by scintillation detection of autologous ¹¹¹In-platelets. Sequential carotid injury produced a thrombus more than 50% greater in volume in the second (3149±2053x10⁶/cm²) relative to the first injured artery (2081±1552x10⁶/cm²; P=0.04) in control pigs. This augmentation was inhibited by intravenous lovastatin which acutely reduced platelet deposition (944±246x10⁶/cm²) relative to saline control (P=0.02). Flow chamber closure times increased on average by 2.45-fold in response to whole blood lovastatin incubation. Lovastatin (P<0.05) and simvastatin (P<0.05) reduced platelet dense granule secretion in vitro.

Conclusions— Sequential arterial injury augments the thrombotic response suggesting that the propensity for arterial thrombosis is at least partially acquired. This thrombotic augmentation can be acutely attenuated by intravenous lovastatin which may result from a pleiotropic impact on platelet function. These results appear to be a class effect of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors.

Sequential carotid crush injury augments the thrombus size by 50% when comparing the second to the first carotid injury in control pigs. This augmentation is acutely attenuated by intravenous lovastatin which appears at least in part attributable to platelet inhibition as evidenced by in vitro measures of platelet function.

Key Words: thrombosis • platelets • statins • pleiotropic effects • HMG-CoA reductase inhibitors