title: Acute onset human atrial fibrillation is associated with local cardiac platelet activation and endothelial dysfunction.
abstract: OBJECTIVE
  The purpose of this study was to determine whether acute onset atrial fibrillation (AF), independent of other risk factors, predisposes to an early prothrombotic state.
  
  
  BACKGROUND
  Several risk factors predispose to the hypercoagulable state in human AF, but whether acute onset AF alone is prothrombotic remains unclear.
  
  
  METHODS
  Patients with paroxysmal AF (n = 22) underwent radiofrequency catheter ablation. All patients presented in sinus rhythm. Baseline blood samples were obtained simultaneously from the femoral vein (systemic sample) and the coronary sinus (local cardiac sample). The AF was induced by burst atrial pacing in 14 patients (AF group). A control group (n = 8) underwent atrial pacing at 120 beats/min. Blood samples were recollected after 15 min. Platelet P-selectin expression (CD62) was measured using flow cytometry. Markers of thrombin generation (thrombin antithrombin complex, prothrombin fragment 1.2), inflammation (C-reactive protein, interleukin-6), and nitric oxide were measured using enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Neither local nor systemic platelet activation changed in the control group. In the AF group, local cardiac platelet activation (percent P-selectin [+] platelets) increased significantly (2.2 +/- 0.6% to 2.8 +/- 1.0%, p = 0.007); however, systemic platelet activation did not change. The AF group had increased local thrombin generation (thrombin antithrombin complex: 8.5 +/- 7.6 ng/ml to 33.2 +/- 17.4 ng/ml, p = 0.003; prothrombin fragment 1.2: 95.6 +/- 45.6 micromol/l to 243.8 +/- 120.1 micromol/l, p = 0.003), decreased nitric oxide production (25.2 +/- 10.8 micromol/l to 22.3 +/- 10.0 micromol/l, p < 0.02), and no change in inflammatory markers.
  
  
  CONCLUSIONS
  Human AF causes local cardiac platelet activation within minutes of onset. The results demonstrate how AF alone, independent of other risk factors, may contribute to the hypercoagulable state.
authors.affiliation: Cardiovascular Institute, Loyola University Medical Center, Maywood, Illinois 60153, USA. jakar@lumc.edu
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Akar
authors.forename: Walter
authors.initials: W
authors.lastname: Jeske
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilber
mesh_terms: D000208:Acute Disease; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000503:physiopathology* / Q000601:surgery; D016022:Case-Control Studies; D017115:Catheter Ablation; D004727:Endothelium / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D015539:Platelet Activation; D011516:Prothrombin / Q000378:metabolism*; D012307:Risk Factors; D013917:Thrombin / Q000037:antagonists & inhibitors; D019851:Thrombophilia / Q000097:blood / Q000209:etiology* / Q000503:physiopathology
chemical_list: D009569:Nitric Oxide; D011516:Prothrombin; D013917:Thrombin