Heparin and the nonanticoagulant N-acetyl heparin attenuate capillary no-reflow after normothermic ischemia of the lung
Heparin and the nonanticoagulant N-acetyl heparin attenuate capillary no-reflow after normothermic ischemia of the lung
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DOI：
10.1016/s0003-4975(01)02959-9
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发表时间：
2001-10-01
影响因子：
4.6
通讯作者：
Schäfers, HJ
中科院分区：
文献类型：
--
作者：
Nakamura, T;Vollmar, B;Schäfers, HJ
背景。肺缺血再灌注损伤常发生在体外循环术后、肺血栓动脉内膜切除术后，尤其是肺移植术后。肝素在缺血再灌注损伤中具有保护作用，但出血性疾病的风险可能限制其在各种疾病条件下的使用。因此，我们测试了非抗凝剂n -乙酰肝素（NA）对肺缺血再灌注后损伤的保护作用。经戊巴比妥麻醉、机械通气的Lewis大鼠在插入导管前进行肝素化（100 IU/kg）。此外，动物在缺血前分别给予肝素（200 IU/kg, n = 7）、NA肝素（1.1 mg/kg, n = 7）或生理盐水（对照组，n = 7）。常温缺血So min后，左肺再灌注120 min，或至动物死亡。再灌注10分钟后排除非缺血性右肺。肝素组和na -肝素组再灌注120分钟存活率分别为7 / 7和6 / 7，对照组7 / 0 （p < 0.01）。再灌注30min时，肝素组和na -肝素组升主动脉PaO2血流量和平均体压均显著高于对照组（p < 0.05）。肝素组和na -肝素组肺血管阻力明显降低，肺组织学检查证实有红细胞存在的营养性肺泡毛细血管再灌注。对照组肺标本肺泡毛细血管红细胞缺乏提示毛细血管再灌注失败。肝素和NA肝素对常温缺血后毛细血管无回流具有相似的保护作用。肺的。这表明肝素的保护作用是由不同于其抗凝血活性的特性介导的。因此，非抗凝剂n -乙酰肝素可能是一种安全的治疗肺缺血再灌注损伤的新方法，而不会增加出血性并发症的风险。(C) 2001年由胸外科医生协会。
Background. Ischemia-reperfusion injury of the lung frequently occurs after cardiopulmonary bypass, after pulmonary thromboendarterectomy, and especially after lung transplantation. Heparin is known to be protective in ischemia-reperfusion injury but the risk for bleeding disorders may restrict its use in a variety of diseased conditions. Therefore, we tested the efficiency of nonanticoagulant N-acetyl (NA) heparin to protect from post-ischemic reperfusion injury of the lung.Methods. Pentobarbital-anesthetized, mechanically ventilated Lewis rats were heparinized (100 IU/kg) before insertion of catheters. Additionally, animals received either heparin (200 IU/kg; n = 7), NA heparin (1.1 mg/kg; n = 7), or saline (control, n = 7) before ischemia. After normothermic ischemia for So minutes, the left lung was reperfused for 120 minutes, or until the death of the animal. The nonischemic right lung was excluded after 10 minutes of reperfusion.Results. Survival rate at 120 minutes of reperfusion was 7 of 7 and 6 of 7 in the heparin and the NA-heparin group, but 0 in 7 in the control group (p < 0.01). At 30 minutes of reperfusion, PaO2 blood flow through the ascending aorta and mean systemic blood pressure were also significantly higher in the heparin and the NA-heparin group when compared with the control group (p < 0.05). Pulmonary vascular resistance was significantly lower in the heparin and the NA-heparin groups, and histologic examination of the lungs from these groups confirmed reperfusion of nutritive alveolar capillaries by the presence of red blood cells. Lack of red blood cells in the alveolar capillaries of lung specimens from the control group indicated failure of capillary reperfusion.Conclusions. Heparin and NA heparin exert similar protection against capillary no-reflow after normothermic ischemia. of the lung. This implies that the protective eff ect of heparin is mediated by properties different from its anticoagulant activity. Thus the nonanticoagulant N-acetyl heparin may pose a safe new therapeutic approach in lung ischemia-reperfusion injury without increasing the risk of hemorrhagic complications. (C) 2001 by The Society of Thoracic Surgeons.