title: Is cardiopulmonary bypass a reason for aspirin resistance after coronary artery bypass grafting?
abstract: OBJECTIVE
  'Off-pump' coronary artery bypass grafting (OPCAB) is an alternative to conventional coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). While midterm results after OPCAB have become available, systematic studies of changes in platelet function after OPCAB are still missing. Since we have previously shown that oral aspirin treatment (100mg) does not achieve sufficient platelet inhibition in the majority of patients operated on with CPB, we hypothesized that bypass surgery without CPB (off-pump coronary artery bypass, OPCAB) causes less impairment of platelet inhibition by aspirin. The aim of this study was to investigate platelet function and the antiplatelet effect of aspirin after off-pump coronary artery bypass grafting in comparison with conventional on-pump surgery.
  
  
  METHODS
  We compared platelet function (in vitro aggregation and thromboxane formation) before and at days 1 and 5 after coronary artery bypass grafting, performed with (n=15) or without (n=14) CPB. Oral aspirin treatment (100mg/d) was started at day 1 after surgery.
  
  
  RESULTS
  After a 5 day oral treatment with aspirin, platelet aggregation was inhibited significantly in OPCAB-patients to 55.7+/-16.3% of control before surgery (P<0.05), whereas aggregation remained unchanged after CPB (105.8+/-26.9% of control before surgery; P>0.05). Since aspirin primarily inhibits platelet thromboxane formation, thromoboxane was determined after in vitro aggregation. According to platelet aggregation, thromboxane formation was only inhibited significantly after OPCAB (29.2+/-13.0% of control before surgery, P<0.05), but not after CPB (74.5+/-21.4% of control before surgery, P>0.05). This resistance to aspirin after CPB may be caused by an increased release of new platelets which are competent to form thromboxane, since the number of platelets decreased from 237+/-11x10(3)/microl before CPB to 174+/-13x10(3)/microl at day 1 after surgery and increased significantly the following days reaching 303+/-17x10(3)/microl at day 5. Platelet counts of patients operated on without CPB showed no significant changes (236+/-16x10(3)/microl before OPCAB, 220+/-16x10(3)/microl at day 1 and 266+/-31x10(3)/microl at day 5 after surgery).
  
  
  CONCLUSIONS
  The antiplatelet effect of aspirin is largely impaired after CPB, but not after CABG without CPB. Hence, increased platelet turnover after CPB seems to contribute to aspirin resistance, since an increased number of platelets might be competent to form thromboxane within the dosing intervals.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Heinrich-Heine-University, Düsseldorf, Germany. hohlfeld@uni-duesseldorf.de
authors.forename: Norbert
authors.initials: N
authors.lastname: Zimmermann
authors.forename: Muhammed
authors.initials: M
authors.lastname: Kurt
authors.forename: Angela
authors.initials: A
authors.lastname: Wenk
authors.forename: Joachim
authors.initials: J
authors.lastname: Winter
authors.forename: Emmeran
authors.initials: E
authors.lastname: Gams
authors.forename: Thomas
authors.initials: T
authors.lastname: Hohlfeld
mesh_terms: D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002315:Cardiopulmonary Bypass; D002478:Cells, Cultured; D001026:Coronary Artery Bypass / Q000379:methods*; D047549:Coronary Artery Bypass, Off-Pump; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count; D011182:Postoperative Care; D011184:Postoperative Period; D013931:Thromboxanes / Q000096:biosynthesis
chemical_list: D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D001241:Aspirin