Summary

The failure of aspirin to inhibit platelet function has been documentedin patients undergoing coronary artery bypass graft(CABG) surgery , but the causes of “aspirin-resistance” remainuncertain.The aim of this study was to investigate the efficacy ofaspirin in patients undergoing CABG surgery receiving either100 mg or 325 mg of oral aspirin for 5-days.Platelet function wastested the day before surgery and on day+1 and day+5, andevaluated by changes in collagen-induced thromboxane-A2(TxA2) release and platelet aggregation following stimulationwith collagen, ADP and epinephrine. In all patients, baseline plateletaggregation was significantly inhibited by pre-incubationwith in vitro aspirin (150 µmol/l), with a mean reduction inTxA2-release of = 95.5% (82.3,99.1). After 5-days of oral aspirin,platelet aggregation was significantly inhibited, and was not further inhibited by in vitro aspirin. Oral aspirin was also associatedwith a = 99.5% (97.8, 99.7) reduction in TxA2-release, andwith the reversal of the second-phase of ADP-induced aggregationwhich is TxA2-dependent. In addition a single-dose of325mg aspirin on the first post-operative morning may have agreater inhibitory effect on collagen-induced aggregation than100mg aspirin.Western blot analysis provided no evidence forthe presence of COX-2 in platelets, while the up-regulation ofp38-MAPK following platelet-stimulation and surgery was seen.The inhibition of COX-2 (NS398) or p38-MAPK (SB203580) activitydid not affect platelet aggregation and TxA2-release onday+5. In summary, there was no evidence for inherent or acquiredaspirin-resistance in this surgical population,or for the involvementof either COX-2 or p38-MAPK.