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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 In-platelets. Sequential carotid injury produced a thrombus more than 50% greater in volume in the second (3149±2053×10/cm) relative to the first injured artery (2081±1552×10/cm; P=0.04) in control pigs. This augmentation was inhibited by intravenous lovastatin which acutely reduced platelet deposition (944±246×10/cm) 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.

Original languageEnglish (US)
Pages (from-to)1271-1276
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number9
DOIs
StatePublished - Sep 2009

Fingerprint

Hydroxymethylglutaryl CoA Reductases
Lovastatin
Thrombosis
Blood Platelets
Swine
Wounds and Injuries
Therapeutics
Carotid Artery Injuries
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Carotid Arteries
Oxidoreductases
Arteries

Keywords

  • HMG-CoA reductase inhibitors
  • Platelets
  • Pleiotropic effects
  • Statins
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Inhibition of platelet-rich arterial thrombus in vivo : Acute antithrombotic effect of intravenous HMG-CoA reductase therapy. / Obi, Chike; Wysokinski, Waldemar; Karnicki, Krzystof; Owen, Whyte G.; McBane, Robert D.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 29, No. 9, 09.2009, p. 1271-1276.

Research output: Contribution to journalArticle

Obi, Chike ; Wysokinski, Waldemar ; Karnicki, Krzystof ; Owen, Whyte G. ; McBane, Robert D. / Inhibition of platelet-rich arterial thrombus in vivo : Acute antithrombotic effect of intravenous HMG-CoA reductase therapy. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2009 ; Vol. 29, No. 9. pp. 1271-1276.
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