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The thromboresistant mechanism of Heparin surface and its application to membrane oxygenator

肝素表面的抗血栓机制及其在膜式氧合器中的应用

基本信息

批准号：
62480330
负责人：
KODAMA Kenji
金额：
$ 3.2万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

We have conducted research work on the thromboresistant mechanism of Heparin surface and its application to membrane oxygenator in collaboration with the Karolinska Institute in Sweden. The results we have obtained are as follows;1. The heparin coating did not take up or exert Factor Xa inhibition by itself. With antithrombin III(AT) adsorbed on both high and low affinity heparin the surface had the capacity to inhibit Factor Xa exposed to the surface. It was demonstrated that the density of AT on both high and low affinity heparin determines the Factor Xa inhibition capacity whereas the amount of AT on high affinity sites limits the rate of the reaction.2. The Factor Xa and thrombin inhibitory capacity were similar in low wall shear rate segments which were obtained by compressing a segment of the surface-heparinized arterio-venous shunts. In high wall shear rate segments, the thrombin inhibitory capacity was decreased, thus indicating that the AT-mediated inhibition of the serine protease is dependent upon the wall shear rate.3. It was demonstrated that an extracorporeal arterio-venous bypass circulation with surface-heparinized membrane oxygenator can be performed for at least 24 hours without any systemic heparinization in dogs.4. It was confirmed that an extracorporeal veno-venous bypass circulation call be done as well under the same experimental conditions as above.5. Consequently we have concluded that the surface-heparinized extracorporeal circuit with membrane oxygenator is an effective and useful system for tile respiratory support in the treatment of the patients with respiratory failure and this system is also applicable for the perioperative patients with difficult airways.6. In the case of the tracheal resection and reconstruction we prepared this system for the respiratory support, but as it was unnecessary to use the system we kept it standby.

我们与瑞典卡罗林斯卡研究所合作，对肝素表面的抗血栓机制及其在膜式氧合器中的应用进行了研究。实验结果如下：1.肝素包衣本身并未摄取或抑制凝血因子Xa。由于抗凝血酶III(AT)同时吸附在高亲和力和低亲和力的肝素上，其表面具有抑制Xa因子暴露的能力。结果表明，高亲和力肝素和低亲和力肝素上AT的浓度决定了凝血因子Xa的抑制能力，而高亲和力部位AT的含量限制了反应速度。经表面肝素化的动静脉分流管加压后，低切变率节段的凝血因子Xa和凝血酶抑制能力相似。在高剪切率节段，凝血酶抑制能力降低，表明AT介导的丝氨酸蛋白酶抑制作用依赖于壁剪切率。实验证明，使用表面肝素化的膜式氧合器进行体外动静脉转流至少可以持续24小时，而不需要进行任何全身肝素化。证实在相同的实验条件下，体外静脉-静脉转流也是可行的。因此，我们认为表面肝素化体外循环加膜式氧合器是治疗呼吸衰竭患者的一种有效、实用的呼吸支持系统，该系统也适用于围手术期呼吸道困难的患者。在气管切除和重建的情况下，我们准备了这个系统用于呼吸支持，但由于不需要使用该系统，我们将其保持待机状态。