title: Influence of antithrombin on ischemia/reperfusion injury in the isolated blood-free perfused rat heart.
abstract: BACKGROUND
  Antithrombin (AT) is well known as an important inhibitor of the coagulation system. An interesting new hypothesis is that antithrombin exerts specific anti-inflammatory effects by stimulating the production of prostacyclin in endothelial cells. Recent studies report beneficial influence on ischemia/reperfusion injury in several organs. These effects are independent of the coagulation system. We investigated the influence of antithrombin on ischemia/reperfusion injury and prostacyclin release in the isolated rat heart. Since the perfusion of the hearts was without blood, the used model essentially describes effects of antithrombin on endothelial cells.
  
  
  METHODS
  Experiments were performed using the temperature-controlled and pressure-constant Langendorff apparatus. The hearts of 32 male Sprague-Dawley rats were subjected to 20 min of global ischemia followed by 30 min of reperfusion. Antithrombin was administered in three different concentrations (1, 4 and 8 U/ml) 15 min prior to global ischemia. Cardiac contractility parameters and biochemical parameters were measured.
  
  
  RESULTS
  Treatment with antithrombin did not increase the release of prostacyclin significantly after ischemia. Antithrombin at a concentration of 8 U/ml led to a significant increase in creatine kinase (CK; p<0.05) and troponin I (p<0.05), whereas measurements of lactate dehydrogenase (LDH) revealed no significant differences between treated and untreated hearts.
  
  
  CONCLUSIONS
  Our study shows that antithrombin did not reduce ischemia/reperfusion injury in the isolated heart, and prostacyclin is not significantly released following antithrombin treatment. High concentrations of antithrombin, however, might have a negative influence on the reperfused heart. The underlying mechanism remains unclear.
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, The Leopold-Franzens University of Innsbruck, Austria. josef.margreiter@uibk.ac.at
authors.forename: Josef
authors.initials: J
authors.lastname: Margreiter
authors.forename: Markus
authors.initials: M
authors.lastname: Mittermayr
authors.forename: Johannes
authors.initials: J
authors.lastname: Mair
authors.forename: Angelika
authors.initials: A
authors.lastname: Hammerer-Lercher
authors.forename: Jordan
authors.initials: J
authors.lastname: Kountchev
authors.forename: Anton
authors.initials: A
authors.lastname: Klingler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schobersberger
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D011464:Epoprostenol / Q000096:biosynthesis; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D019210:Troponin I / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000991:Antithrombins; D019210:Troponin I; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase