Effects of Heparin and ε-Aminocaproic Acid in Dogs on Plasmin- 125I Generation in Response to Urokinase Injections and Venous Injury

Abstract

A B S T R A C T The isotopic method described previously for quantification of plasmin-jI by disc gel electrophoresis was modified by inclusion of euglobulin precipitation to expand its applicability to plasmas containing low radioactivity of plasmin-I and plasminogen-'I. It was found that the euglobulin precipitation method precipitates 72.4±2.1 (SD) % of both plasmin-'I and plasminogen-I. Using this method and plasminogen-I as a tracer, studies were first made of the effects of heparin and e-aminocaproic acid in dogs on plasmin-mI generation in responese to a single injection of urokinase and to venous injury; second, of the effects of venous occlusion and thrombosis on plasmin-'I generation; and third, in vitro studies of plasminogen-'I affinity to fibrin and its activation in blood clots. The venous injury was produced by the damage of venous endothelium by an injection of 90% phenol and the thrombosis by a thrombin injection into an occluded vein. Heparin and e-aminocaproic acid under the present experimental conditions inhibited about 78 and 100%, respectively of plasmin-I generation by the urokinase injection. Similar inhibitory effects of heparin and e-aminocaproic acid were observed on plasmin-;I generation in response to venous injury.The venous occlusion caused a small degree of plasmin-'I generation, but thrombin thrombosis did not seem to stimulate the generation of plasmin-;I.

Physicochemical and Biological Properties of Human and Canine Plasmins

“…The electrophoretic analyses of the sample (Fig. 6a) showed in essential agreement with our previous results (1)(2)(3) that the predominant plasmin found at 5 min was one that has the electrophoretic mobility identical to that of our peak 3 plasmin (Figs. 5 and 6).…”

“…A single kind of ['"I]plasmin is generated from ['I]-plasminogen in vivo when urokinase is injected into dogs (1)(2)(3). This was also true in vitro when [jI]plasminogen was incubated with urokinase at 380C for 5 min (1)(2)(3).…”

“…This was also true in vitro when [jI]plasminogen was incubated with urokinase at 380C for 5 min (1)(2)(3). The ['"I]plasmin generated both in vivo and in vitro was detected and quantified by the method devised in this laboratory (1)(2)(3), using disc gel electrophoresis (4).…”

“…However, considerable degrees of affinity were observed with a2-macroglobulin (Fig. 12) (1,2), and the plasma half-life of generated…”

Urine Plasmin-Like Substances as an Index of Kidney Allograft Rejections

“…An initial process of the acute rejection is presumed to be destruction of vascular endothelial cells in graft tissue by both antibodies and lymphocytes against histocompatibility antigens. In this process, plasminogen would be activated into plasmin by plasminogen activator released from the injured endothelial cells (20,28), which contain much of the plasminogen activator (12,29). The injury of the endothelial cells causes platelet aggregation and fibrin clotting (4,11).…”