Thrombin inactivation and the effects of antithrombin and heparin in a recirculating Langendorff preparation.
A recirculating Langendorff preparation was developed in order to study the effects of antithrombin III (AT) and heparin on thrombin inactivation in the capillary bed. Using this technique, rat hearts were shown to inhibit approximately 50% of the recirculated thrombin, while surface-bound thrombin displayed no enzymatic activity towards recirculated fibrinogen. By displacing thrombin bound to the endothelial surface with Polybrene, thrombin enzymatic activity was found to be equally active against a synthetic chromogenic substrate (S-2238) and fibrinogen. This indicates that thrombin bound to the capillary endothelial surface is not coagulantly active, but, when displaced from the endothelium, its coagulant activity is retained. Hearts pretreated with AT or heparin had no effect on thrombin inhibition or surface-bound thrombin, although there was an uptake of both substances to the heart. These findings are in contrast with the results obtained from large vessel preparations, where pretreatment with AT increased thrombin inhibition and also demonstrated lower levels of surface-bound thrombin, and where heparin eluted endogenous AT from the endothelium. It is concluded that AT plays a more important role in the inhibition of thrombin on large vessels than in the microcapillary system where thrombomodulin is the major inactivator of thrombin.
Nydahl
S
S
Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
Frebelius
S
S
Swedenborg
J
J
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000032:analysis; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008833:Microcirculation; D010100:Oxygen / Q000032:analysis; D010477:Perfusion; D011188:Potassium / Q000032:analysis; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013917:Thrombin / Q000037:antagonists & inhibitors*
D002245:Carbon Dioxide; D000990:Antithrombin III; D006493:Heparin; D013917:Thrombin; D011188:Potassium; D010100:Oxygen