• Tuberculosis and Respiratory Diseases
• /
• v.40 no.5
• /
• pp.474-482
• /
• 1993

Background: As a physiologic plasminogen activator, tissue-type plasminogen activator (t-PA) could induce effective thrombolysis in massive pulmonary embolism, without the risk of systemic hemorrhage. However, therapeutic doses of t-PA has been associated with systemic lytic state, and fibrin selectivity may be influenced by the dosing regimen of t-PA. To investigate the effects of duration of t-PA infusion on blood coagulation system, we performed this study. Method: In a canine model of pulmonary embolism, which was induced by injection of autologous blood clots, we administered equal doses of t-PA (1 mg/kg) over 15 minutes in $t-PA_{15}$ group, over 180 minutes in $t-PA_{180}$ group, and only saline in control group. Then serial blood samplings were made to check complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, fibrin, plasminogen, ${\alpha}_2$-antiplasmin, coagulation factor V and VIII, and fibrin(ogen) degradation products. Results: 1) In all 3 groups, complete blood count showed same changes. Hemoglobin, hematocrit and platelet count decreased, but WBC count increased. 2) Prothrombin time, activated partial thromboplastin time, and thrombin time were prolonged during 15-60 minutes after t-PA administration in $t-PA_{15}$ group, and from 30 minutes through 180 minutes after administration in $t-PA_{180}$ gorup. 3) Fibrin, ${\alpha}_2$-antiplasmin, and cogulation factor V and VIII decreased in both $t-PA_{15}$ and $t-PA_{180}$ group, but returned to basal levels earlier in $t-PA_{15}$ group. 4) Fibrin(ogen) degradation products increased after pulmonary embolism in all groups, and further increased in both $t-PA_{15}$ and $t-PA_{180}$ groups after t-PA infusion. But more pronounced increment was noted in $t-PA_{180}$ gorup. Conclusion: In pulmonary embolism, the shorter (15 minutes) infusion of t-PA would have less risk of systemic hemorrhage than the longer (180 minutes) infusion when the doses is equal. And, this suggests that manipulating the duration of t-PA infusion can reduce the risk of major bleeding.

• Tuberculosis and Respiratory Diseases
• /
• v.40 no.2
• /
• pp.123-134
• /
• 1993

Background: Tissue-type plasminogen activator is a physiologic activator, which has high affinity for fibrin and is activated by fibrin. Because of these properties, t-PA has the potential to induce effective thrombolysis without producing a systemic lytic state. In practice, however, therapeutically efficacious doses of t-PA has been associated with the development of a systemic lytic state. As experience with t-PA has accumulated, it has suggested that the fibrin selectivity is influenced by the dose and duration of t-PA infusion, and many studies have performed in an attempt to optimize the duration of t-PA regimen. Methods: This study was designed to assess the thrombolytic efficacy of t-PA and the differences of two dosing regimens of t-PA (infusion of 1 mg/kg t-PA over 15 or 180 minutes) in a canine model of pulmonary embolism, induced by injection of radioactive autologous blood clots. By continuously counting over both lung fields with a external gamma counter, we correlated rate and extent of pulmonary thrombolysis with corresponding pulmonary hemodynamics in addition to the gas analyses of arterial and mixed venous blood. Results: 1) While total clot lysis was similar ($36.2{\pm}3.3%$ and $39.6{\pm}2.3%$ respectively, p>0.05) when t-PA was infused over 15 or 180 minutes, the rate of lysis during infusion was markedly increased with the shorter infusion ($81.4{\pm}16.8%/hr$ vs $37.3{\pm}2.4%/hr$, p<0.05). 2) The duration of thrombolysis was $63.3{\pm}22.2$ minutes although t-PA was administered over 15 minutes, and it was only $148.5{\pm}14.0$ minutes in case of the infusion over 180 minutes (p<0.05). 3) The increased rate of thrombolysis with the shorter infusion was accompanied by a faster amelioration of cardiopulmonary impairment from pulmonary embolism (p<0.05). Conclusion: It is concluded that the shorter (15 minutes) infusion of t-PA is superior to the longer (180 minutes) infusion when the dose is equal, in consideration of the faster improvement in cardiopulmonary impairment from pulmonary embolism.

• KSBB Journal
• /
• v.14 no.6
• /
• pp.724-730
• /
• 1999

Characteristics and enzyme activity comparison was made between urokinase isolated from urine and pro-urokinase separated from CHO(Chinese Hamster Ovary) cell culture broth. Both of purified urokinase and pro-urokinase resulted 54Kd single band in electrophoresis. Urokinase which was proved as a single molecule by gel filtration showed two separated 33Kd and 21Kd bands by 2-mercaptoethanol reduction. Isoelectric forcusing resulted same pl value of 8.6 for both of them. N-terminal amino acid sequence of urokinase after 159th Ile was Ile-Gly-Gly-Glu-Phe-Thr-Thr-Ile-Glu which was different from another N-terminal sequence of Ser-Asn-Glu-Leu-His-Gln-Val-Pro-Ser-Asn. Thrombolytic activities of both of them were propotional to the enzyme concentration. Urokinase showed thrombolytic activities in an short period of reaction time. Pro-urokinase, however, showed high thrombolytic activity for 2 hours or longer period of reaction time.