Influence of antithrombin on ischemia/reperfusion injury in the isolated blood-free perfused rat heart.
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.
Margreiter
Josef
J
Department of Anesthesia and Intensive Care Medicine, The Leopold-Franzens University of Innsbruck, Austria. josef.margreiter@uibk.ac.at
Mittermayr
Markus
M
Mair
Johannes
J
Hammerer-Lercher
Angelika
A
Kountchev
Jordan
J
Klingler
Anton
A
Schobersberger
Wolfgang
W
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
D000991:Antithrombins; D019210:Troponin I; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase