The study for the analysis of mechanism and the inhibition of allograft rejection

研究1我们开发了一种新的心脏长期保存装置，它结合了简单的浸泡和冠状动脉灌流。在以前的研究中，我们报道了抑制促炎症细胞因子，如肿瘤坏死因子-α(Tumor Neckine-α)和白介素1-β(Interleulin-1β，IL-1)，可以改善移植后的结果。在这项研究中，我们评估了在犬移植模型中，使用我们的冠脉持续灌注器进行长期保存，结合抑制促炎细胞因子，是否改善了供体心脏功能。本研究采用成年杂种犬作为研究对象。成年杂种犬分为冠脉灌注组(CP组)和FR167653组(FR-CP组)，每组7只。CP组采用4℃UW溶液浸泡和冠脉灌注。FR-CP组用4℃UW液加20 mg/L抗炎剂进行浸泡和冠脉灌注。因此，血流动力学…再灌注后FR-CP组糖原含量显著高于CP组(p&lt；0.05)，且超微结构显示FR-CP组较CP组糖原保存良好。使用本装置的持续灌流和浸泡结合抑制促炎细胞因子的联合保存方法改善了移植后的供心功能。研究2WE先前报道了使用我室研制的装置用于长期心脏保存的持续冠脉灌注法的优越性。然而，心肌水肿是这种保存方法的问题之一。在这项研究中，我们尝试了一项对比研究，即12小时的冠状动脉持续灌流和11小时的简单浸泡后1小时的冠脉灌流，以评价长期保存心脏的合适方法。本研究选用体重10-15公斤的HBD犬。将移植物分为两组，CP组(n=6)仅用4℃溶液持续冠脉灌流保存移植物，SI+CP组(n=6)在相同溶液简单浸泡11h后再加1h冠脉灌流保存移植物。TX后，两组的血流动力学维持在基线水平的70-90%左右，HR、CO和E&lt；max及Gt；在两组间无显著差异。SI+CP组心肌含水量显著低于CP组(P<0.05)。在简单的浸泡保存后进行额外的短期冠状动脉灌注是获得满意的长期心脏保存的类似方法。研究3据报道，COX-2在缺血再灌注损伤中起重要作用，并且在同种异体心脏移植排斥反应中COX-2mRNA和蛋白表达上调。FK3311是COX-2激活的抑制因子。本研究旨在评价FK3311抑制环氧合酶-2对犬移植后缺血再灌注损伤和改善供心功能的作用。成年杂种犬被使用。5只犬在再灌注前静脉注射FK3311(3 mg/kg)，对照组(n=5)静脉注射赋形剂。FK组的血流动力学恢复率显著高于对照组(p&lt；0.05)。因此，抑制COX-2可改善长期保存后的移植心功能。较少

Study No. 1We developed a new apparatus for long-term heart preservation that combines simple immersion with coronary perfusion. In a previous study, we reported that suppression of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleulcin-1β (IL-1β), improved results after transplantation. In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion, combined with suppression of proinflammatory cytokines, improves donor heart function following transplantation in a canine model. Adult mongrel dogs were used in this study. Adult mongrel dogs were divided into two groups: the coronary perfusion (CP) group (n=7) and the FR167653 (FR-CP) group (n=6). In the CP group, a 4℃ UW solution was used for both immersion and coronary perfusion. In the FR-CP group, a 4℃ UW solution supplemented with 20 mg/L of the anti-inflammatory agent FR167653 was used for both immersion and coronary perfusion. As a result, hemodynamics … More after reperfusion were significantly higher (p<0.05) in the FR-CP group than in the CP group, and electron microscopic studies showed that glycogen was well preserved in the FR-CP group as compared with the CP group. The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of proinflammatory cytokines improves donor heart function following transplantation.Study No. 2We had previously reported the superiority of the continuous coronary perfusion method using the apparatus developed by our department for long-term heart preservation. However, myocardial edema was one of the problems following this preservation method. In this study, we attempted a comparative study of 12-hr continuous coronary perfusion and 1-hr coronary perfusion following 11-hr simple immersion to evaluate the suitable method for long-term heart preservation. HBD dogs, weighing 10-15kg, were used in this study. Grafts were divided into the two groups; in the CP group grafts (n=6) were preserved by continuous coronary perfusion only with a 4℃ Celsior solution, and the SI+CP (n=6) group grafts were preserved with additional 1-hr coronary perfusion following 11-hr simple immersion with the same solution. Hemodynamics after Tx were maintained around about 70-90% of baseline levels in the both groups, and there were no significant differences in HR, CO, and E_<max> between the two groups. On the other hand, myocardial water content was significantly (p<0.05) lower in the SI+CP group than in the CP group. Additional short-term coronary perfusion following simple immersion preservation is a comparable method for the satisfied long-term heart preservation.Study No.3It has been reported that COX-2 plays an important role in ischemia-reperfusion injury and that COX-2 mRNA and protein expression were upregulated during cardiac allograft rejection. FK3311 is a suppressor of COX-2 activation. The purpose of this study was to evaluate the effectiveness of inhibiting COX-2 with FK3311 for the minimization of ischemia-reperfusion injury and for the improvement of donor heart function following transplantation in a canine model. Adult mongrel dogs were used. FK3311 (3 mg/kg) was administered intravenously to five dogs prior to reperfusion, while vehicle was administered intravenously to a control group (n = 5). The recovery rates of hemodynamics were significantly (p < 0.05) better in the FK-treated dogs than in the controls Therefore, the inhibition of COX-2 improves transplanted cardiac function following long-term preservation. Less