Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
J Heart Lung Transplant. 2013 May;32(5):505-10. doi: 10.1016/j.healun.2013.02.007. Epub 2013 Mar 15.
Donor lung thrombi are considered an important etiology for primary graft dysfunction in lung transplantation. We hypothesized that thrombolysis before lung transplantation could alleviate ischemia-reperfusion injury. This study was designed to evaluate the effect of the fibrinolytic agent plasmin on lungs damaged by thrombi in an ex vivo lung perfusion (EVLP) system.
Rats were divided into control, non-plasmin, and plasmin groups (n = 7 each). In the control and plasmin groups, cardiac arrest was induced by withdrawal of mechanical ventilation without heparinization. Ventilation was restarted 150 minutes after cardiac arrest. The lungs were flushed, and the heart and lungs were excised en bloc. The lungs were perfused in the EVLP system for 60 minutes, and plasmin or placebo was administered upon EVLP initiation.
Fibrin/fibrinogen degradation products in the perfusate were significantly higher in the plasmin group than in the control and non-control groups (p < 0.001 for both). Plasmin administration significantly decreased pulmonary vascular resistance (plasmin vs non-plasmin, p = 0.011) and inhibited the exacerbation of dynamic compliance (plasmin vs non-plasmin, p = 0.003). Lung weight gain was less in the plasmin group than in the non-plasmin group (p = 0.04).
Our results confirmed that plasmin administration in an EVLP model dissolved thrombi in the lungs, resulting in reconditioning of the lungs as assessed by various physiologic parameters.
供体肺血栓被认为是肺移植中原发性移植物功能障碍的一个重要病因。我们假设在肺移植前进行溶栓可以减轻缺血再灌注损伤。本研究旨在评估纤溶剂纤溶酶对体外肺灌注（EVLP）系统中血栓损伤肺的作用。
大鼠分为对照组、非纤溶酶组和纤溶酶组（每组 7 只）。在对照组和纤溶酶组中，通过停止机械通气而不给予肝素来诱导心脏骤停。心脏骤停后 150 分钟重新开始通气。冲洗肺，整块取出心脏和肺。将肺在 EVLP 系统中灌注 60 分钟，并在 EVLP 开始时给予纤溶酶或安慰剂。
纤溶酶组灌流液中的纤维蛋白/纤维蛋白原降解产物明显高于对照组和非对照组（两者均 p < 0.001）。纤溶酶给药显著降低肺血管阻力（纤溶酶与非纤溶酶，p = 0.011），并抑制动态顺应性的恶化（纤溶酶与非纤溶酶，p = 0.003）。纤溶酶组的肺重量增加明显低于非纤溶酶组（p = 0.04）。
我们的结果证实，纤溶酶在 EVLP 模型中的给药溶解了肺中的血栓，导致各种生理参数评估的肺再 conditioning。
