Prewitt R M, Hoy C, Kong A, Gu S A, Greenberg D, Cook R, Chan S M, Ducas J
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Am Rev Respir Dis. 1990 Feb;141(2):290-5. doi: 10.1164/ajrccm/141.2.290.
We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA.
我们比较了重组组织型纤溶酶原激活剂（rtPA）和尿激酶（UK）对犬微小肺血栓栓塞症的溶栓及肺血流动力学影响。用放射性自体血凝块栓塞犬，以升高平均肺动脉压（从13毫米汞柱升至34毫米汞柱，p<0.005）并降低心输出量（从2.5升/分钟降至1.6升/分钟，p<0.005）。将四组每组六只犬进行治疗。我们采用了两种剂量的UK，即30,000 U/kg（UK30）和60,000 U/kg（UK60），以及两种剂量的rtPA，即1 mg/kg（rtPA1）和2 mg/kg（rtPA2）。药物在15分钟内输注完毕。用γ相机持续对双侧肺野计数，评估肺血栓溶解的速率和程度。与UK治疗相比，两种rtPA方案均显著增加了血栓溶解。UK30和UK60的平均总肺血栓溶解率分别为14%和23%，rtPA1和rtPA2分别为35%和43%。与血栓溶解增加相对应，rtPA使肺血流动力学改善最为明显。从90分钟至3小时，两种rtPA方案的肺动脉压均显著低于两种UK方案。这些结果表明，至少在所采用的模型中，与UK治疗相比，rtPA的肺血栓溶解及相应的血流动力学改善最为显著。
