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Thromb Haemost 2006; 95(02): 354-361
DOI: 10.1160/TH05-05-0377
Animal Models
Schattauer GmbH

Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina

Benjamin Bierbach   *
1   Deptartment of Cardiothoracic and vascular surgery
,
Georg Horstick   *
2   2nd Medical Clinic, Johannes Gutenberg-University Mainz, Germany
,
Oliver Berg
2   2nd Medical Clinic, Johannes Gutenberg-University Mainz, Germany
,
Axel Heimann
3   Institute for Neurosurgical Pathophysiology, Johannes Gutenberg-University Mainz, Germany
,
Thomas Münzel
2   2nd Medical Clinic, Johannes Gutenberg-University Mainz, Germany
,
Christian-Friedrich Vahl
1   Deptartment of Cardiothoracic and vascular surgery
,
Oliver Kempski
3   Institute for Neurosurgical Pathophysiology, Johannes Gutenberg-University Mainz, Germany
,
Harald Darius
2   2nd Medical Clinic, Johannes Gutenberg-University Mainz, Germany
› Author AffiliationsFinancial support: We gratefully acknowledge Sanofi-Synthelabo and Bristol-Myers Squibb for supplying clopidogrel.
Further Information

Publication History

Received 30 May 2005

Accepted after resubmission 09 January 2005

Publication Date:
28 November 2017 (online)

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Summary

Application of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG. Therefore, the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions. The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0.1 mg/kg or5 mg/kg), aspirin (1 mg/kg or 7 mg/kg) or LDC (0.1 mg/kg clopidogrel and 1 mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min. CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, −48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg, −65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0.1 mg/kg) plus aspirin (1 mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (−70%, p<0.05). Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application. The effect occurs before inhibition of platelet aggregation is detectable.

Keywords

Aspirin - clopidogrel - platelets - acute coronary syndrome - coronary artery bypass grafting

* Authors contributed equally to this work.


 

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