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长期保存心脏的装置，它结合了简单的浸泡和冠状动脉灌注。在以前的研究中，我们报道了抑制促炎细胞因子，如肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1β），可改善移植后的结果。在这项研究中，我们评估了是否长期保存使用我们的设备连续冠状动脉灌注，结合抑制促炎细胞因子，提高供体心脏功能移植后的犬模型。本研究使用成年杂种犬。将成年杂种犬分为两组：冠状动脉灌注（CP）组（n=7）和FR 167653（FR-CP）组（n=6）。CP组采用4℃ UW液浸泡和冠状动脉灌注。FR-CP组采用4℃ UW液加20 mg/L抗炎剂FR 167653进行浸泡和冠状动脉灌注。因此，血液动力学 关于我们 FR-CP组再灌注后肝糖原含量显著高于CP组（p<0.05），电镜观察显示FR-CP组肝糖原保存较好。联合保存方法的连续灌注和浸泡使用我们的设备结合抑制促炎细胞因子提高供体心脏功能后transplantation.Study No.2We以前曾报道的优越性的连续冠状动脉灌注方法使用的设备开发的由我们部门长期保存心脏。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12小时连续冠状动脉灌注和1小时冠状动脉灌注后11小时简单浸泡的比较研究，以评估长期心脏保存的合适方法。本研究中使用了体重10- 15 kg的HBD犬。将移植物分为两组，CP组（n=6）仅用4℃ Celsior溶液连续冠状动脉灌注保存移植物，SI+CP组（n=6）在用相同溶液简单浸泡11 h后再用1 h冠状动脉灌注保存移植物。两组治疗后血流动力学均维持在基线水平的70-90%左右，两组之间的HR、CO和E_2无显著差异<max>。另一方面，SI+CP组的心肌含水量显著低于CP组（p&lt;0.05）。研究No.3研究表明，考克斯-2在缺血再灌注损伤中起重要作用，考克斯-2 mRNA和蛋白表达在心脏移植排斥反应中上调。FK 3311是考克斯-2激活的抑制剂。本研究的目的是在犬移植模型中评价使用FK 3311抑制考克斯-2以最小化缺血-再灌注损伤和改善供体心脏功能的有效性。使用成年杂种犬。再灌注前，5只犬静脉给予FK 3311（3 mg/kg），对照组（n = 5）静脉给予溶媒。FK治疗组的血流动力学恢复率明显优于对照组（p &lt; 0.05）。因此，抑制考克斯-2可改善移植心脏长期保存后的功能。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