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

Y. Takeda; T. R. Parkhill; M. Nakabayashi

doi:10.1172/JCI107086

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

Y. Takeda, T. R. Parkhill, and M. Nakabayashi

Published October 1, 1972 - More info

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Abstract

The isotopic method described previously for quantification of plasmin- ¹²⁵I by disc gel electrophoresis was modified by inclusion of euglobulin precipitation to expand its applicability to plasmas containing low radioactivity of plasmin- ¹²⁵I and plasminogen- ¹²⁵I. It was found that the euglobulin precipitation method precipitates 72.4±2.1 (sd)% of both plasmin- ¹²⁵I and plasminogen- ¹²⁵I. Using this method and plasminogen- ¹²⁵I as a tracer, studies were first made of the effects of heparin and ε-aminocaproic acid in dogs on plasmin- ¹²⁵I generation in responese to a single injection of urokinase and to venous injury; second, of the effects of venous occlusion and thrombosis on plasmin- ¹²⁵I generation; and third, in vitro studies of plasminogen- ¹²⁵I 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 ε-aminocaproic acid under the present experimental conditions inhibited about 78 and 100%, respectively of plasmin- ¹²⁵I generation by the urokinase injection. Similar inhibitory effects of heparin and ε-aminocaproic acid were observed on plasmin- ¹²⁵I generation in response to venous injury. The venous occlusion caused a small degree of plasmin- ¹²⁵I generation, but thrombin thrombosis did not seem to stimulate the generation of plasmin- ¹²⁵I. The in vitro studies showed that plasminogen- ¹²⁵I does not have a specific affinity to fibrin and is incorporated into blood clots in approximately equal concentrations as those in serum during clotting processes, and that blood clots per se do not stimulate plasmin- ¹²⁵I generation. These results suggest that injured veins release considerable amounts of vascular plasminogen activators into circulation and that these play an important role in thrombus dissolution in vivo.