This research project consists of methods for evaluating six thrombolytic agents in the dog model. The streptokinase-activator complexes of plasminogen, mini-plasminogen, and the plasmin B-chain will be compared with urokinase, tissue plasminogen activator and the acyl-plasminogen-streptokinase complex by both local and systemic infusion of each activator. Clot lysis will be determined using radioactivity measurements on a standardized clot, as well as blood flow, clot weight, and visual clot inspection. The relative effectiveness of pre-infusion of Lys-plasminogen prior to systemic clot lysis will also be determined. Chromogenic substrate assays for functional plasminogen, free protease activity, plasminogen activator activity, alpha-2-plasmin inhibitor activity, and plasmin generation rates will be determined in plasmas obtained from a diverse patient population, including acute myocardial infarction victims, burn victims, premature infants, cancer patients, postoperative patients, and patients undergoing thrombolytic therapy in order to evaluate these kinetic assays as prognostic tools, and to determine whether there is a link between """"""""variant"""""""" plasminogen and an altered hematologic or thrombotic condition in these patients. Plasminogen will be isolated from those patients identified as possessing an abnormal plasminogen and after tryptic digestion, high performance liquid chromatography will be used to isolate the abnormal peptide which will be sequenced to locate the amino acid substitution. Methods are also described for isolating site specific monoclonal antibodies which will be used to determine which regions in plasminogen are critical for the binding of activators, and to delineate the immunological structure of plasminogen. Methods for isolating and characterizing the various forms of vascular plasminogen activator are also described. Our results should further our knowledge of in vivo clot lysis, plasminogen variance, and postoperative venous thrombosis.
| Summaria, L; Pavlovic, B; Sandesara, J (1989) An anti-plasminogen antibody preparation that inhibits the activation of human plasminogen but enhances the activator activity of the B-chain-streptokinase complex. Thromb Res 54:1-15 |
| Summaria, L (1989) Comparison of human normal, full-term, fetal and adult plasminogen by physical and chemical analyses. Haemostasis 19:266-73 |
| Summaria, L; Boreisha, I; Barlow, G H et al. (1987) The isolation and characterization of a ternary human plasmin B-chain-streptokinase-plasminogen complex. Thromb Haemost 58:772-7 |
