Localization of tissue plasminogen activator on experimental thrombi in rats.
The localization of tissue plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA) on thrombi was investigated in disseminated intravascular coagulation rats (DIC rats) induced by thrombin. One hour after the intravenous infusion of thrombin to rats, the plasma fibrinogen level decreased, while the plasminogen activator activity in the plasma euglobulin fraction increased. The whole body autoradiography was studied after an injection of [125I]fibrinogen in DIC rats. The high radioactivity which indicated the presence of microthrombi was observed in the renal cortex, liver, spleen and lung. Furthermore, a large venous thrombus with higher radioactivity was observed in the abdominal vena cava. These results show that the thrombin-treated animal is one of the best DIC models. After the intravenous administration of [125I]t-PA, the autoradiograms of DIC rats showed a radioactivity in the blood and much higher radioactivities in the renal cortex, spleen and lung in comparison with the normal rat. However, there was no difference in the distribution of [125I]u-PA between normal and DIC rats at all. The strong radioactivity of [125I]t-PA but not [125I]u-PA was observed on the surface of large thrombus in the vena cava. These results suggest that t-PA localizes more preferentially on microthrombi than u-PA. The ratio of the radioactivity in the tissue to that in the blood was calculated to compare quantitatively the localization of [125I]t-PA and [125I]u-PA on microthrombi formed in organs.(ABSTRACT TRUNCATED AT 250 WORDS)
Kimata
H
H
Tokyo Research Laboratories Kowa Co., Ltd., Japan.
Nakajima
K
K
Koide
T
T
Yamamoto
S
S
Kondo
S
S
D000818:Animals; D001345:Autoradiography; D004211:Disseminated Intravascular Coagulation / Q000209:etiology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D010960:Plasminogen Activators / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000493:pharmacokinetics; D013917:Thrombin / Q000008:administration & dosage; D013927:Thrombosis / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics*; D014568:Urokinase-Type Plasminogen Activator / Q000493:pharmacokinetics
D007457:Iodine Radioisotopes; D012709:Serum Albumin; D010960:Plasminogen Activators; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator