| Differences in thrombolytic effects in accordance with dosing- resimens of tissue- type plasminogen activator in experimental pulmonary embolism. |
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Hee Soon Chung1, Ho Jung Kim2, Yong Chol Han3 |
1Department of Internal Medicine, Seoul City Boramae Hospital and Seoul National University College of Medicine, Seoul, Korea
2Department of Internal Medicine, College of Medicine, Hanlim University, Seoul, Korea
3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea |
| 실험적 폐색전증에서 조직형플라스미노겐활성체의 투여방법에 따른 혈전용해효과의 차이 |
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| Abstract |
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 selecti vi t y is influenced by the dose and duration of t-PA infusion, and many studies have performed in an attempt to optim ize the dura ti on 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 a rteria l and mixed venous blood.
Results
1) While total clot lysis was similar (36.2±3.3% and 39.6 ±2.3% respectively, p >0.05) when t-PA was infused over 15 or 180 minutes, the rate of Iysis during infusion was markedly increased with the shorter infusion (8 1.4±16.8% / hr vs 37.3 ± 2.4 %/ hr, p < 0.05). 2) The duration of thrombolysis was 63.3±22.2 minutes although t.PA was administered over 15 minutes, and it was only 148.5± 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.
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| Key Words:
Duration on of t-PA infusion, Total clot Iysis, Rate of thrombolysis, Pulmonary embolism |
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