title: Effect of remote ischaemic conditioning on coagulation and fibrinolysis.
abstract: BACKGROUND
  Remote ischaemic conditioning (RIC) reduces infarct size and may improve prognosis in patients with acute myocardial infarction. To explore the potential mechanisms, we investigated the effects of RIC on coagulation and fibrinolysis.
  
  
  METHODS
  Interventional crossover study including 30 healthy drug-naïve males. Participants were exposed to a sham intervention (visit 1) and to RIC (visit 2 and 3) induced by intermittent arm ischaemia through four cycles of 5-min inflation of a blood pressure cuff followed by 5-min deflation. Prior to visit 3, all participants received aspirin 75mg daily for seven days. Blood samples were obtained at baseline as well as 5 and 45min after intervention. Whole blood coagulation was assessed by thromboelastometry (ROTEM®) and thrombin generation. Fibrinolysis was evaluated by clot turbidity-lysis, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1).
  
  
  RESULTS
  No differences were found in clot initiation, clot propagation or clot strength evaluated by ROTEM® (all p-values≥0.98). During aspirin treatment, clot initiation and clot propagation decreased after RIC evaluated by ROTEM® EXTEM® clotting time (p=0.04) and ROTEM® EXTEM® maximum velocity (p=0.03). After sham and RIC, thrombin generation declined as evaluated by reduced endogenous thrombin potential (RIC: p=0.001) and peak (RIC: p=0.01). After RIC during aspirin treatment, changes in thrombin generation were inconsistent; increased peak (p=0.04) and time to peak (p<0.001) and a decrease in lag-time (p<0.001). Clot lysis time was prolonged both after sham and after RIC (p<0.001). After RIC, PAI-1 levels declined (p=0.03), but t-PA levels also declined after all interventions (p-values≤0.04).
  
  
  CONCLUSIONS
  RIC did not have substantial effects on coagulation or fibrinolysis compared to sham. Overall, aspirin did not influence the results.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jacobina
authors.initials: J
authors.lastname: Kristiansen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Erik L
authors.initials: EL
authors.lastname: Grove
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Rise
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søs
authors.initials: S
authors.lastname: Neergaard-Petersen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Würtz
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Steen Dalby
authors.initials: SD
authors.lastname: Kristensen
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: am.hvas@dadlnet.dk.
authors.forename: Anne-Mette
authors.initials: AM
authors.lastname: Hvas
mesh_terms: D000328:Adult; D001132:Arm / Q000098:blood supply*; D001241:Aspirin / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D018592:Cross-Over Studies; D063285:Fibrin Clot Lysis Time; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D007511:Ischemia / Q000097:blood*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood* / Q000628:therapy*; D013916:Thrombelastography; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D001241:Aspirin
keywords: Aspirin; Blood coagulation; Fibrinolysis; Remote ischemic conditioning; Thromboelastometry