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Title: Radiation effects on the fibrinolytic system and their relation to hemorrhagic diathesis and increased endothelial permeability

Thesis/Dissertation ·
OSTI ID:5123202

This study was designed to investigate the effects of wholebody X-irradiation on the fibrinolytic system, the causes of radiation-induced changes in plasmin (fibrinolytic) activity, and the contribution of increased plasmin activity to increased capillary (endothelial) permeability and hemorrhagic diathesis. The parameters evaluated using adult, male, Rochester ex-Wistar rats were: (1) plasmin, plasminogen, and plasminogen activator levels in plasma within one month after 425, 655, or 885 rad and at 3.5, 7 and 12 months after 425 rad, by a modified caseinolytic method; (2) tissue plasminogen activator activity (TPAA) in heart, kidneys, lungs, liver, pancreas and spleen, by a fibrin plate method (885 rad); (3) vascular permeability, by a radioisotopic method (885 rad); and (4) gross hemorrhagic response, scored for severity. The dose-dependent changes described in plasmin, plasminogen and plasminogen activator were multi-phasic. Epsilon-amino-caproic acid (0.3 gm/kg body weight) prevented the immediate and early radiation effects on these fibrinolytic components, and partially inhibited the later effects (within one month) whether administered only as a single injection before irradiation or maintained by daily water intake thereafter. The kidneys, spleen and pancreas were markedly susceptible to radiation-induced changes in TPAA. The lungs and liver showed significant changes in capillary permeability, which correlated positively with changes in vascular volume and blood plasmin and plasminogen activator levels. Increased plasmin (fibrinolytic) activity, superimposed on a hemostatic apparatus already impaired because of thrombocytopenia, contributed to hemorrhagic diathesis in acute radiation sickness.

Research Organization:
Rochester Univ., NY (USA)
OSTI ID:
5123202
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English

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