Inhibition of platelet-rich arterial thrombus in vivo: acute antithrombotic effect of intravenous HMG-CoA reductase therapy.
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.


RESULTS
The first carotid artery was crush-injured and harvested after 30 minutes. Pigs then received intravenous lovastatin (100 microg/kg bolus+100 microg/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 (111)In-platelets. Sequential carotid injury produced a thrombus more than 50% greater in volume in the second (3149+/-2053 x 10(6)/cm(2)) relative to the first injured artery (2081+/-1552 x 10(6)/cm(2); P=0.04) in control pigs. This augmentation was inhibited by intravenous lovastatin which acutely reduced platelet deposition (944+/-246 x 10(6)/cm(2)) 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.
Obi
Chike
C
University of Pittsburgh School of Medicine, Pittsburgh, Penn., USA.
Wysokinski
Waldemar
W
Karnicki
Krzystof
K
Owen
Whyte G
WG
McBane
Robert D
RD
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D020212:Carotid Artery Injuries / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008148:Lovastatin / Q000008:administration & dosage*; D015388:Organelles / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D013552:Swine; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin