Hirsh J, Cade J F, Regoeczi E, Gent M, Buchanan M R, Hynes D M
J Clin Invest. 1974 Oct;54(4):782-91. doi: 10.1172/JCI107818.
Thrombolytic agents may be useful in acute pulmonary embolism, but their optimal dosage remains uncertain. We have examined the relative efficacy of heparin and different doses of streptokinase, either alone or in combination, in acute experimental pulmonary embolism. A standardized massive embolus of autologous blood clot incorporating canine [(125)I]-fibrinogen was given to 40 dogs; the degree of resolution after 24 h was quantitated by measuring the radioactivity in the lungs and was compared with detailed postmortem observations. The amount of residual embolus was 49% in control animals, 28% after heparin (200 U/kg loading dose and 800 U/kg/24 h maintenance dose), and 6% after high dose streptokinase (250,000 U loading dose and 100,000 U/h maintenance dose); it was 31% after low dose streptokinase (25,000 U loading dose and 10,000 U/h maintenance dose), 7% after low dose streptokinase with heparin, 14% after very low dose streptokinase (5,000 U/h without a loading dose) with heparin, and 9% after short course streptokinase (250,000 U loading dose and no maintenance dose) with heparin. The combination of heparin and low doses or brief courses of streptokinase appeared to be synergistic and produced as much resolution as did standard high dose streptokinase alone. The enhanced resolution of pulmonary emboli in heparin-treated animals may have been due to the prevention by heparin of further deposition of fibrin on the embolus. It appears that dosage regimens of thrombolytic therapy other than those in current use may be worthy of clinical examination.
溶栓剂可能对急性肺栓塞有用，但它们的最佳剂量仍不确定。我们研究了肝素和不同剂量链激酶单独或联合使用在急性实验性肺栓塞中的相对疗效。将包含犬[(125)I] - 纤维蛋白原的自体血凝块制成的标准化大量栓子给予40只狗；24小时后通过测量肺部放射性对溶解程度进行定量，并与详细的尸检观察结果进行比较。对照动物中残余栓子量为49%，肝素治疗后（负荷剂量200 U/kg，维持剂量800 U/kg/24 h）为28%，高剂量链激酶治疗后（负荷剂量250,000 U，维持剂量100,000 U/h）为6%；低剂量链激酶（负荷剂量25,000 U，维持剂量10,000 U/h）治疗后为31%，低剂量链激酶与肝素联合治疗后为7%，极低剂量链激酶（无负荷剂量，5,000 U/h）与肝素联合治疗后为14%，短疗程链激酶（负荷剂量250,000 U，无维持剂量）与肝素联合治疗后为9%。肝素与低剂量或短疗程链激酶联合使用似乎具有协同作用，产生的溶解效果与单独使用标准高剂量链激酶相同。肝素治疗动物中肺栓塞溶解增强可能是由于肝素防止了纤维蛋白在栓子上进一步沉积。看来，目前使用的溶栓治疗方案以外的其他方案可能值得临床研究。
