EFFICACY OF CONTINUOUS REGIONAL ARTERIAL INFUSION WITH LOW-MOLECULAR-WEIGHT HEPARIN FOR SEVERE ACUTE PANCREATITIS IN A PORCINE MODEL
EFFICACY OF CONTINUOUS REGIONAL ARTERIAL INFUSION WITH LOW-MOLECULAR-WEIGHT HEPARIN FOR SEVERE ACUTE PANCREATITIS IN A PORCINE MODEL
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DOI：
10.1097/shk.0000000000000129
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发表时间：
2014-05-01
期刊：
影响因子：
3.1
通讯作者：
Li, Jie-shou
中科院分区：
文献类型：
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作者：
Ke, Lu;Ni, Hai-bin;Li, Jie-shou
目的：肝素或其衍生物的使用已被证明对治疗重症急性胰腺炎（SAP）有益。然而，传统静脉注射方式的药物难以到达胰腺组织，并且可能因SAP启动后的凝血和微循环障碍而导致出血并发症。在本研究中，我们旨在评估采用持续局部动脉输注 (CRAI) 技术给予 SAP 猪模型的低分子量肝素 (LMWH) 的效果。方法：根据基线测量，18只动物分为三组：CRAI组（通过放置的动脉导管输注LMWH）、静脉组（通过中心静脉导管输注LMWH）和SAP对照组。我们采用逆行导管内输注牛磺胆酸钠来诱导 SAP。研究了动物的整体血流动力学特征、尿量、全身氧合以及炎症和血清生化参数。实验结束时，对胰腺、肠和肺进行组织学检查。结果：与其他两组相比，持续局部动脉输注 LMWH 显着稳定了血流动力学特征，改善了全身氧合和外周灌注，减轻了胰腺的组织学损伤（特别是坏死范围），并下调了炎症反应。此外，CRAI 组的血清 D-二聚体水平也下降最显着（最终静脉组为 474±144 vs. 664±155 µg/L，对照组为 945±351 µg/L），部分表明研究组的凝血障碍得到改善。 CRAI 组未观察到出血并发症，而静脉组有两只动物出现胃肠道出血。结论：持续局部动脉灌注LMWH在SAP病程中疗效显着，且安全性高。需要使用这种新型疗法进行人体研究来评估临床环境中的这些潜在益处。
Objective: Administration of heparin or its derivatives has been proved to be beneficial in the treatment of severe acute pancreatitis (SAP). However, drugs administered by conventional intravenous way are difficult to reach the pancreatic tissue and may cause bleeding complications due to coagulation and microcirculatory disturbance following initiation of SAP. In this study, we aimed to assess the effects of low-molecular-weight heparin (LMWH) administered with continuous regional arterial infusion (CRAI) technique in a porcine model of SAP. Methods: Following baseline measurements, 18 animals were divided into three groups: CRAI group (LMWH infused through placed arterial catheter), venous group (LMWH infused through central venous catheter), and SAP control group. We used retrograde intraductal infusion of sodium taurocholate to induce SAP. Global hemodynamic profiles, urine output, systemic oxygenation, and inflammatory and serum biochemical parameters of the animals were studied. At the end of the experiment, histological examination of pancreas, intestine, and lung was performed. Results: Continuous regional arterial infusion with LMWH remarkably stabilized hemodynamic profiles, improved systemic oxygenation and peripheral perfusion, alleviated histological injury of pancreas (especially for the necrosis scale), and downregulated inflammatory response when compared with the other two groups. Moreover, serum D-dimer level also decreased most significantly in the CRAI group (474±144 vs. 664±155 µg/L in the venous group and 945±351 µg/L in the controls at the end), partly indicating ameliorated coagulation disorders in the study group. No bleeding complication was observed in the CRAI group, whereas two animals in the venous group presented gastrointestinal hemorrhage. Conclusions: Continuous regional arterial infusion with LMWH exhibits strong therapeutic effects in the course of SAP with great safety. Human studies using this novel therapy are required to assess these potential benefits in the clinical setting.