Skrzypchak Amy M, Lafayette Nathan G, Bartlett Robert H, Zhou Zhengrong, Frost Megan C, Meyerhoff Mark E, Reynolds Melissa M, Annich Gail M
Department of General Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0243, USA.
Perfusion. 2007 May;22(3):193-200. doi: 10.1177/0267659107080877.
The gold standard for anticoagulation during extracorporeal circulation (ECC) remains systemic heparinization and the concomitant risk of bleeding in an already critically ill patient could lead to death. Normal endothelium is a unique surface that prevents thrombosis by the release of antiplatelet and antithrombin agents. Nitric oxide (NO) is one of the most potent, reversible antiplatelet agents released from the endothelium. Nitric oxide released from within a polymer matrix has been proven effective for preventing platelet activation and adhesion onto extracorporeal circuits. However, the critical NO release (NO flux) threshold for thrombus prevention during ECC has not yet been determined. Using a 4-hour arteriovenous (AV) rabbit model of ECC, we sought to find this threshold value for ECC circuits, using an improved NO-releasing coating (Norel-b). Four groups of animals were tested at variable NO flux levels. Hourly blood samples were obtained for measurement of arterial blood gases, platelet counts, fibrinogen levels and platelet function (via aggregometry). A custom-built AV circuit was constructed with 36 cm of poly(vinyl)chloride (PVC) tubing, a 14 gauge (GA) angiocatheter for arterial access and a modified 10 French (Fr) thoracic catheter for venous access. The Norel-b coating reduced platelet activation and thrombus formation, and preserved platelet function - in all circuits that exhibited an NO flux of 13.65 x 10(10) mol x cm(-2) x min(-1). These results were significant when compared with the controls. With the Norel-b coating, the NO flux from the extracorporeal circuit surface can be precisely controlled by the composition of the polymer coating used, and such coatings are shown to prevent platelet consumption and thrombus formation while preserving platelet function in the animal.
体外循环（ECC）期间抗凝的金标准仍然是全身肝素化，而在已经危重病患者中伴随的出血风险可能导致死亡。正常内皮是一种独特的表面，通过释放抗血小板和抗凝血酶剂来防止血栓形成。一氧化氮（NO）是内皮释放的最有效的可逆抗血小板剂之一。从聚合物基质中释放的一氧化氮已被证明可有效防止血小板激活和粘附到体外循环装置上。然而，ECC期间预防血栓形成的关键NO释放（NO通量）阈值尚未确定。我们使用改进的NO释放涂层（Norel-b），通过4小时的兔动静脉（AV）ECC模型，试图找到ECC回路的这个阈值。在不同的NO通量水平下对四组动物进行了测试。每小时采集血样以测量动脉血气、血小板计数、纤维蛋白原水平和血小板功能（通过凝集测定法）。使用36厘米的聚氯乙烯（PVC）管、一个用于动脉通路的14号（GA）血管导管和一个改良的10法式（Fr）胸导管用于静脉通路，构建了一个定制的AV回路。在所有表现出13.65×10¹⁰摩尔×厘米⁻²×分钟⁻¹的NO通量的回路中，Norel-b涂层减少了血小板激活和血栓形成，并保留了血小板功能。与对照组相比，这些结果具有显著性。使用Norel-b涂层，体外循环回路表面的NO通量可以通过所用聚合物涂层的组成精确控制，并且这种涂层在动物中显示出可防止血小板消耗和血栓形成，同时保留血小板功能。
