title: Role of tissue factor-mediated coagulation in ischemia/ reperfusion-induced injury of Langendorf-perfused rabbit hearts.
abstract: BACKGROUND
  Production of oxygen free radicals, and activation of neutrophils and plasma complement contribute to myocardial reperfusion injury, but the role of coagulation has not been assessed.
  
  
  OBJECTIVE
  To characterize tissue-factor-mediated generation of thrombin and its association with tissue injury during reperfusion from normothermic ischemia of isolated, Langendorf-perfused rabbit hearts.
  
  
  METHODS
  Activation of coagulation was assessed by addition of 12% rabbit plasma and human fibrinogen to Krebs-Henseleit-buffer perfusate with measurement of levels of human fibrinopeptide A (hFPA) in the heart effluent as an index of thrombin-mediated formation of fibrin.
  
  
  RESULTS
  Concentrations of hFPA in the effluent were minimal during non-ischemic perfusion (5 +/- 5 ng/ml, n=6) and during 50 min of ischemia (13 +/- 3 ng/ml, n=6), but increased markedly during the first 20 min of reperfusion (to 41 +/- 29 ng/ml, P=0.03 versus before reperfusion). Addition to the perfusate of 10 microg/ml recombinant human tissue-factor-pathway inhibitor, the physiologic inhibitor of tissue-factor-mediated coagulation, abolished increases in the level of hFPA after reperfusion. However, indexes of myocardial injury manifested during reperfusion, including decrease in recovery of left ventricular pressure developed, increase in left ventricular end-diastolic pressure, and increase in activity of creatine kinase in the heart effluent, were not improved by anticoagulation with recombinant human tissue-factor-pathway inhibitor.
  
  
  CONCLUSIONS
  Our results do not support the hypothesis that coagulation plays a major role in ischemia/reperfusion injury of Langendorf-perfused rabbit hearts.
authors.affiliation: Wisconsin Heart and Vascular Clinics, Milwaukee, USA.
authors.forename: L
authors.initials: L
authors.lastname: Armaganian
authors.forename: G
authors.initials: G
authors.lastname: Kam
authors.forename: P R
authors.initials: PR
authors.lastname: Eisenberg
authors.forename: K B
authors.initials: KB
authors.lastname: Schechtman
authors.forename: D R
authors.initials: DR
authors.lastname: Abendschein
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology; D003402:Creatine Kinase / Q000097:blood; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005344:Fibrinopeptide A / Q000032:analysis; D006321:Heart / Q000502:physiology; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D013917:Thrombin / Q000096:biosynthesis; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D005343:Fibrinolytic Agents; D008074:Lipoproteins; D010446:Peptide Fragments; C081249:tissue factor pathway inhibitor (1-161); D005344:Fibrinopeptide A; D013925:Thromboplastin; D003402:Creatine Kinase; D013917:Thrombin