title: Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery.
abstract: OBJECTIVE
  Anti-inflammatory effects of tranexamic acid and aprotinin, used to abate perioperative blood loss, are reported and might be of substantial clinical relevance. The study of messenger ribonucleic acid synthesis provides a valuable asset in evaluating the inflammatory pathways involved.
  
  
  METHODS
  Whole-blood messenger ribonucleic acid expression of 114 inflammatory genes was compared pre- and postoperatively in 35 patients randomized to receive either placebo, tranexamic acid, or aprotinin. These results were further confirmed by reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Of the 23 genes exhibiting independently altered postoperative gene expression levels, 8 were restricted to the aprotinin group only (growth differentiation factor 3, interleukin 19, interleukin 1 family member 7, transforming growth factor α, tumor necrosis factor superfamily 10, tumor necrosis factor superfamily 12, tumor necrosis factor superfamily 13B, vascular endothelial growth factor α), whereas both aprotinin and tranexamic acid altered gene expression of 3 genes as compared with placebo (FMS-related tyrosine kinase 3 ligand, growth differentiation factor 5, interferon-α8). In general, less upregulation of pro-inflammatory, and more upregulation of anti-inflammatory, genes was observed for patients treated with antifibrinolytics. Gene expression affected by aprotinin coded mostly for proteins that function through serine proteases.
  
  
  CONCLUSIONS
  This study demonstrates that the use of tranexamic acid and aprotinin results in altered inflammatory pathways on the genomic expression level. We further demonstrate that the use of aprotinin leads to significant attenuation of the immune response, with several inhibitory effects restricted to the use of aprotinin only. The results aid in a better understanding of the targets of these drugs, and add to the discussion on which antifibrinolytic can best be used in the cardiac surgical patient.
authors: Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands. a.f.l.later@lumc.nl
authors: Alexander F L
authors: AF
authors: Later
authors: Laura S
authors: LS
authors: Sitniakowsky
authors: Joost A
authors: JA
authors: van Hilten
authors: Leo
authors: L
authors: van de Watering
authors: Anneke
authors: A
authors: Brand
authors: Nico P M
authors: NP
authors: Smit
authors: Robert J M
authors: RJ
authors: Klautz
mesh_terms: D000368:Aged; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D007611:Aprotinin / Q000627:therapeutic use*; D006348:Cardiac Surgical Procedures; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000276:immunology / Q000601:surgery*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014148:Tranexamic Acid / Q000627:therapeutic use*; D015854:Up-Regulation
chemical_list: D000933:Antifibrinolytic Agents; D010919:Placebos; D012333:RNA, Messenger; D014148:Tranexamic Acid; D007611:Aprotinin