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165 Thrombus age and thrombolysis with tissue plasminogen activator in rats
71
P. wendt, W. Siebels, A. GrUner and G. Bliirel (Institut fiir Experimzntelle Cbirunjie der Tectmiscben Universitit Miinchen) A depression of the intraperitoneal fibrinolytic activity due to surgical trauna provides the basis for adhesion formation. Tbfzt-efonz, the prophylactic local application of fibrinolysis activators s&sms to be prwtising. Possible side effects include the interference With surgical means of ti ssufs adaptation such as resorb&le suture materi al s or fibrin glue. These effects were exanined in an in-vitro study. Resorbable suture materials (Cat Plain and Cbrun Cat, Set-q Wiessner; Vicryl-Polyglactin 910 ti PUS-Polydioxznon, Etbicon; Bexon-Polyglycolic acid, Dexpn) wet-e in&&d over 7 days in physiologic saline and saline B+ loo0 IU/ml Streptckinase/Streptodbmase (SK/SD, Varidase - Cyananid
164
Fibrinolytic therapy of thromboembolic vascular occlusions: Streptokinase versus Urokinase F. Grahenwoezerand W. Dock II Chirurgische Univ. Klinik Wien, Austria Until today only a few studies have been published which compare the clinical efficacy of streptokinase(SK) and urokinase (UK). Therefore we present our experience with 87 patients treated with these fibrinolytic agents. Both agents were injected directly into the thrombus. If thrombosis dated back less than 2 months a primary success rate of 81% could he reachedin the UK group and in 55% of the SK group. If the occlusion was older than 2 months the-overall successrate came up to only 38%. In 44 casesof complete occlusion of the
165 THRCMBUS T ISSUE
AGE AND PLASMINOGEN
THRCMBOLYSIS ACT IVATDR
IN
WITH RATS.
L. J. Ga. Frade, M. Loren, M. Torrado, J. L. Na varro. S. Hematologfa. Hospital Ram6n y Cajal. Madrid. Spain. Changes in thrombus related to age, are an important determinant of the outcome of thrombolysis. To study this effect we used: Recombinant tissue plasminogen activator (R-tPA) on a inferi or vena cava thrombus model. After seven days of the surgical procedure, the animals were inA ected with 0. 5 ml of: sterile saline (150 mM) (n= 40) or R-tPA (15~10~ IU/3OOg rat weight) (n= 27), given i. v. via a tail vein. After 1 hour blo od samples were collected. The inferior vena ca_ va thrombus was r”emoved, kept at 37gC for 24h. and then weighed. In vitro clot lysis assays with 1251 incorporated previously to clot Fibrinogen-
Lederle) as well as in titrated hunan plasma Reid plasma + SK/So (N = 7). The bredting strengths of surgical knots in either material inc&&.ed in SK/So were at a level from 86,3 to 107 % of that of materials incubated in the control msdia. Fran ttte fibrinogen preparations of carmercial fibrin glues (Tissucol, Imnno and Beriplast, Bebring) fibrin plates were cast (0,3 % fibrin and 1 % agarose w/v in (kren’s buffer). In pun&d boles 20 pi of SK/SD dilution series in NaCl and plasma (0 - 500 IU/ml) were applied. After irc&ation at 37°C for 17 h the lysis areas ranged dose dependently ft-un 0 - 102 m#. Fibrinolysis was greatly ~X&IXI in plates containing 1,3 KIU of aprotinin/ml gel (O-18 m$) and was ccepletely blazked with 15 KIU/ml. This pmtection was not reduced upon repeated elution With the tile volunz of Tris t&fer (3 x 12 h) before SK/SO application. Conclusicui: SK/SD does not attack resorb&le suture materials witbin 7 d. Fibrin glue is protected by lcw m~xlts of aprotinin (15 KIU/ml as catpared to loo0 - 3ooo KIU/ml in routine application). The inhibitor is bourni to the fibrin gel and not readily eluted.
peripheral vascular bed a revascularisation could be reachedin 63% of the patients treated with UK and in only 29% by using SK. In 52 patients long term results after a mean interval of 20 months (3 - 44 months) could be evaluated.In the patient group with good primary results satisfying long term results were obtained in 69% whereas in caseswith incomplete primary revascularisation good long term results came up to 30%. Concerning these results there existed no significant differences in both groups. Summarizing theseresults it seemsobvious that treatment with UK provides better results than with SK and should be recommended for fibrinolytic therapy.
fort-ration Fibrinogen
were alsc evaluated at 1,3,7 days. was measured according to Ratnoff,
t-PA according to Verheijen, D-D EL ISA method. In thrombus aged in viva for 7 days ed a significant decrease in thrombus 0. 01). Though there was no bleeding
concentration
decreased
significantly.
dimer
by
an
R-tPA show_ weight (PC , fibrinogn
After
1h
injected t-PA was not detected in plasma. Human plasma clot lysis assays showed an obvious effect for R-tPA (40 lU/ml) measured as D-D di mer prcduction, a range from 5000 to 200 UI/ml release a similar amount of c. p. m. The t-PA effect was abolished by a rabbit polyclonal anti body against R-tPA. It is concluded that R-tPA is an efficient throm_ bolytic agent in 7 days cld experimental thromb Lower doses seem possible to be useful. us.
P. wendt, W. Siebels, A. GrUner and G. Bliirel (Institut fiir Experimzntelle Cbirunjie der Tectmiscben Universitit Miinchen) A depression of the intraperitoneal fibrinolytic activity due to surgical trauna provides the basis for adhesion formation. Tbfzt-efonz, the prophylactic local application of fibrinolysis activators s&sms to be prwtising. Possible side effects include the interference With surgical means of ti ssufs adaptation such as resorb&le suture materi al s or fibrin glue. These effects were exanined in an in-vitro study. Resorbable suture materials (Cat Plain and Cbrun Cat, Set-q Wiessner; Vicryl-Polyglactin 910 ti PUS-Polydioxznon, Etbicon; Bexon-Polyglycolic acid, Dexpn) wet-e in&&d over 7 days in physiologic saline and saline B+ loo0 IU/ml Streptckinase/Streptodbmase (SK/SD, Varidase - Cyananid
164
Fibrinolytic therapy of thromboembolic vascular occlusions: Streptokinase versus Urokinase F. Grahenwoezerand W. Dock II Chirurgische Univ. Klinik Wien, Austria Until today only a few studies have been published which compare the clinical efficacy of streptokinase(SK) and urokinase (UK). Therefore we present our experience with 87 patients treated with these fibrinolytic agents. Both agents were injected directly into the thrombus. If thrombosis dated back less than 2 months a primary success rate of 81% could he reachedin the UK group and in 55% of the SK group. If the occlusion was older than 2 months the-overall successrate came up to only 38%. In 44 casesof complete occlusion of the
165 THRCMBUS T ISSUE
AGE AND PLASMINOGEN
THRCMBOLYSIS ACT IVATDR
IN
WITH RATS.
L. J. Ga. Frade, M. Loren, M. Torrado, J. L. Na varro. S. Hematologfa. Hospital Ram6n y Cajal. Madrid. Spain. Changes in thrombus related to age, are an important determinant of the outcome of thrombolysis. To study this effect we used: Recombinant tissue plasminogen activator (R-tPA) on a inferi or vena cava thrombus model. After seven days of the surgical procedure, the animals were inA ected with 0. 5 ml of: sterile saline (150 mM) (n= 40) or R-tPA (15~10~ IU/3OOg rat weight) (n= 27), given i. v. via a tail vein. After 1 hour blo od samples were collected. The inferior vena ca_ va thrombus was r”emoved, kept at 37gC for 24h. and then weighed. In vitro clot lysis assays with 1251 incorporated previously to clot Fibrinogen-
Lederle) as well as in titrated hunan plasma Reid plasma + SK/So (N = 7). The bredting strengths of surgical knots in either material inc&&.ed in SK/So were at a level from 86,3 to 107 % of that of materials incubated in the control msdia. Fran ttte fibrinogen preparations of carmercial fibrin glues (Tissucol, Imnno and Beriplast, Bebring) fibrin plates were cast (0,3 % fibrin and 1 % agarose w/v in (kren’s buffer). In pun&d boles 20 pi of SK/SD dilution series in NaCl and plasma (0 - 500 IU/ml) were applied. After irc&ation at 37°C for 17 h the lysis areas ranged dose dependently ft-un 0 - 102 m#. Fibrinolysis was greatly ~X&IXI in plates containing 1,3 KIU of aprotinin/ml gel (O-18 m$) and was ccepletely blazked with 15 KIU/ml. This pmtection was not reduced upon repeated elution With the tile volunz of Tris t&fer (3 x 12 h) before SK/SO application. Conclusicui: SK/SD does not attack resorb&le suture materials witbin 7 d. Fibrin glue is protected by lcw m~xlts of aprotinin (15 KIU/ml as catpared to loo0 - 3ooo KIU/ml in routine application). The inhibitor is bourni to the fibrin gel and not readily eluted.
peripheral vascular bed a revascularisation could be reachedin 63% of the patients treated with UK and in only 29% by using SK. In 52 patients long term results after a mean interval of 20 months (3 - 44 months) could be evaluated.In the patient group with good primary results satisfying long term results were obtained in 69% whereas in caseswith incomplete primary revascularisation good long term results came up to 30%. Concerning these results there existed no significant differences in both groups. Summarizing theseresults it seemsobvious that treatment with UK provides better results than with SK and should be recommended for fibrinolytic therapy.
fort-ration Fibrinogen
were alsc evaluated at 1,3,7 days. was measured according to Ratnoff,
t-PA according to Verheijen, D-D EL ISA method. In thrombus aged in viva for 7 days ed a significant decrease in thrombus 0. 01). Though there was no bleeding
concentration
decreased
significantly.
dimer
by
an
R-tPA show_ weight (PC , fibrinogn
After
1h
injected t-PA was not detected in plasma. Human plasma clot lysis assays showed an obvious effect for R-tPA (40 lU/ml) measured as D-D di mer prcduction, a range from 5000 to 200 UI/ml release a similar amount of c. p. m. The t-PA effect was abolished by a rabbit polyclonal anti body against R-tPA. It is concluded that R-tPA is an efficient throm_ bolytic agent in 7 days cld experimental thromb Lower doses seem possible to be useful. us.