title: Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery.
abstract: BACKGROUND
  Aspirin inhibits platelet activation and reduces atherothrombotic complications in patients at risk of myocardial infarction and stroke. However, a sufficient inhibition of platelet function by aspirin is not always achieved. The causes of this aspirin resistance are unknown.
  
  
  RESULTS
  Patients undergoing coronary artery bypass grafting (CABG) have a high incidence of aspirin resistance. To evaluate functional and biochemical responses to aspirin, platelet-rich plasma was obtained before and at days 1, 5, and 10 after CABG. Thromboxane formation, aggregation, and alpha-granule secretion were effectively inhibited by 30 or 100 micromol/L aspirin in vitro before CABG, but this inhibition was prevented or attenuated after CABG. Whereas the inhibition of thromboxane formation and aggregation by aspirin in vitro partly recovered at day 10 after CABG, oral aspirin (100 mg/d) remained ineffective. The inducible isoform of cyclooxygenase in platelets, COX-2, has been suggested to confer aspirin resistance. In fact, immunoreactive COX-2 was increased 16-fold in platelets at day 5 after CABG, but the COX-2 selective inhibitor celecoxib did not alter aspirin-resistant thromboxane formation. By contrast, the combined inhibitor of thromboxane synthase and thromboxane receptor antagonist terbogrel equally prevented thromboxane formation of platelets obtained before (control) and after CABG.
  
  
  CONCLUSIONS
  Platelet aspirin resistance involves an impairment of both in vivo and in vitro inhibition of platelet functions and is probably due to a disturbed inhibition of platelet COX-1 by aspirin.
authors.affiliation: Institut für Pharmakologie und Klinische Pharmakologie, UniversitätsKlinikum, Heinrich Heine-Universität, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Zimmermann
authors.forename: A
authors.initials: A
authors.lastname: Wenk
authors.forename: U
authors.initials: U
authors.lastname: Kim
authors.forename: P
authors.initials: P
authors.lastname: Kienzle
authors.forename: A-A
authors.initials: AA
authors.lastname: Weber
authors.forename: E
authors.initials: E
authors.lastname: Gams
authors.forename: K
authors.initials: K
authors.lastname: Schrör
authors.forename: T
authors.initials: T
authors.lastname: Hohlfeld
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D001026:Coronary Artery Bypass; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins; D019007:P-Selectin / Q000096:biosynthesis; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000096:biosynthesis; D013931:Thromboxanes / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D019007:P-Selectin; D011725:Pyridines; D013931:Thromboxanes; D016718:Arachidonic Acid; C112331:terbogrel; D003094:Collagen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; D001241:Aspirin; D007213:Indomethacin