Abstract 1938: Inhibition of Platelet-Rich Arterial Thrombus in vivo: The Acute Antithrombotic Effect of Intravenous HMG CoA Reductase Therapy
Background/Objective: Reduced cardiovascular events with statins have been attributed in part to pleiotropic mechanisms. To test the hypothesis that statins will acutely inhibit platelet thrombus formation, the abrupt effect of intravenous lovastatin on augmentation of thrombotic response to a second vascular injury was assessed in a well-characterized porcine carotid thrombosis model.
Methods: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 minutes before harvesting. Pigs then received intravenous lovastatin (100 μg/kg bolus +100 μg/kg/hour infusion, n=6) or saline (n=14). Thirty minutes after drug initiation, the contralateral artery was injured. Thrombus size was quantified by scintillation detection of autologous 111In-platelets. Platelet function was assessed by dense granule secretion and flow chamber methodologies.
Results: Sequential carotid injury, produced a thrombus nearly 50% greater in volume in the second (2,856±1,596x106/cm2) relative to the first injured artery (1,972±1,054x106/cm2; p=0.02) in control pigs. This augmentation was completely abolish by intravenous lovastatin which acutely and significantly reduced platelet deposition (944±247x106/cm2) relative to saline control (p<0.005). Flow chamber closure times increased on average by 2.45 fold in response to whole blood lovastatin incubation. Lovastatin reduced platelet dense granule secretion by 10–30% in response to thrombin (p<0.05) or convulxin (p=0.06).
Conclusions: When performed sequentially, the first arterial injury enhances thrombotic response of the second injury, which can be inhibited by acute intravenous lovastatin infusion. This antithrombotic effect of intravenous statins may result from an acute pleiotropic impact on platelet function.