Influence of the fast-acting inhibitor of plasminogen activator on in vivo thrombolysis induced by tissue-type plasminogen activator in rabbits. Interference of tissue-derived components.
The influence of endotoxin-induced elevated plasma levels of the fast-acting inhibitor of plasminogen activator (PA-inhibitor) on thrombolysis was investigated in rabbits with a jugular vein thrombus. Infusion of human tissue-type plasminogen activator (t-PA) produced similar degrees of thrombolysis in control and endotoxin-treated rabbits, although no free t-PA could be demonstrated in plasma of endotoxin-treated animals. Infusion of t-PA in an extracorporeal arteriovenous shunt resulted in loss of thrombolytic activity in endotoxin-treated animals but not in control animals. Blood clots superfused in vitro with mixtures of t-PA and normal plasma lysed in contrast to clots superfused with t-PA and PA-inhibitor-rich plasma. However, addition of rabbit lung slices to the plasma surrounding the blood clot, reversed the inhibition of thrombolysis by PA-inhibitor-rich plasma. This indicates that tissue-derived factor(s) are involved in the regulation of in vivo thrombolysis. These hypothetical factor(s) are, however, very unstable in plasma, which has thus far precluded their further characterization.
D000818:Animals; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006023:Glycoproteins / Q000494:pharmacology*; D015849:Plasminogen Inactivators; D011817:Rabbits; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors*
D004731:Endotoxins; D006023:Glycoproteins; D015849:Plasminogen Inactivators; D005337:Fibrin; D010959:Tissue Plasminogen Activator