Pre-treatment of porcine pulmonary xenograft with desmopressin: a novel strategy to attenuate platelet activation and systemic intravascular coagulation in an ex-vivo model of swine-to-human pulmonary xenotransplantation
Pre-treatment of porcine pulmonary xenograft with desmopressin: a novel strategy to attenuate platelet activation and systemic intravascular coagulation in an ex-vivo model of swine-to-human pulmonary xenotransplantation
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DOI：
10.1111/j.1399-3089.2008.00445.x
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发表时间：
2008-02-01
影响因子：
3.9
通讯作者：
Kang, Hee Jung
中科院分区：
文献类型：
--
作者：
Kim, Young Tae;Lee, Hyun Joo;Kang, Hee Jung
背景：血管性血友病因子（vWF）已被认为是异种肺移植中凝血功能障碍的主要原因。1-脱氨基-8-D-精氨酸加压素（DDAVP）预处理供体猪可降低异种肺移植物中vWF的含量。在这里，我们探讨DDAVP预处理的影响，在离体灌注模型的异种肺transplantation.Methods：我们建立并进行离体灌注使用猪肺副叶和新鲜的人全血（n = 12）。一半供体猪在离体灌注前静脉内给予3 μ g/kg DDAVP 3天（DDAVP组），另一半不给药（对照组）。用新鲜血液灌注猪肺1 h，监测以下参数的变化：肺动脉压、肺血管阻力、血细胞计数、纤维蛋白原、抗凝血酶、血小板因子4、D-二聚体、C3 a、C4d和异种反应性IgM。释放的Gal α 1-3Gal异种抗原（α Gal）从猪肺已被灌注，并保留了30分钟与人血进行了评估，通过酶联免疫吸附试验使用α Gal结合lectin.Results：DDAVP和对照组均表现出典型的结果，立即肺功能障碍：肺血管阻力增加和隔离的白细胞和血小板离体灌注后。而DDAVP组血小板第4因子、C3 a、C4d的增加较对照组减弱。结论：DDAVP预输注对供体猪血小板活化及补体/凝血激活均有抑制作用。DDAVP的这些作用可能与异种移植物中猪vWF含量的降低有关。因此，调节供体肺中vWF分泌可能是减少异种肺移植中全身凝血病的另一种治疗方法。
Background: Von Willebrand factor (vWF) has been proposed as a major contributor to the development of coagulopathy in pulmonary xenotransplantation. Pretreatment of donor swine with 1-deamino-8-D-arginine vasopressin (DDAVP), an analog of vasopressin, can reduce the content of vWF in pulmonary xenografts. Here, we investigate the effects of DDAVP pre-treatment in an ex-vivo perfusion model of pulmonary xenotransplantation.Methods: We set up and performed the ex-vivo perfusion using porcine pulmonary accessory lobes and fresh human whole blood (n = 12). Half of the donor swine were given 3 mu g/kg DDAVP intravenously for 3 days before ex-vivo perfusion (DDAVP group) and half of them were left untreated (control group). The porcine lung was perfused with fresh blood for 1 h and changes in the following parameters were monitored: pulmonary arterial pressure, pulmonary vascular resistance, blood cell counts, fibrinogen, antithrombin, platelet factor 4, D-dimer, C3a, C4d, and xenoreactive IgM. The release of Gal alpha 1-3Gal xenoantigen (alpha Gal) from porcine lung which had been perfused and retained for 30 min with human blood was assessed by enzyme-linked immunosorbent assay using alpha Gal-binding lectin.Results: Both DDAVP and control groups showed typical findings of immediate pulmonary dysfunction: an increase of pulmonary vascular resistance and sequestration of leukocytes and platelets after ex-vivo perfusion. However, in the DDAVP group, the increase of platelet factor 4, C3a, and C4d after perfusion was attenuated compared to that in the control group. The release of alpha Gal after blood retention was significantly lower in the DDAVP group than that of the control group.Conclusion: Pre-infusion of DDAVP to the donor swine was beneficial in attenuating platelet activation as well as complement/coagulation activation. These effects of DDAVP are likely to relate to the reduction of porcine vWF content in the xenograft. Therefore, the modulation of vWF secretion in donor lungs could be an additional therapeutic way to reduce systemic coagulopathy in pulmonary xenotransplantation.