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心脏保存装置，将简单浸泡与冠状动脉灌注相结合。在之前的一项研究中，我们报道了抑制促炎细胞因子，如肿瘤坏死因子-α (TNF-α)和白介素-1β (IL-1β)，可以改善移植后的结果。在这项研究中，我们评估了使用我们的设备进行持续冠状动脉灌注的长期保存，并结合抑制促炎细胞因子，是否可以改善犬模型移植后供者的心脏功能。本研究使用成年杂种狗。将成年杂种狗分为冠状动脉灌注（CP）组（n=7）和FR167653 （FR-CP）组（n=6）。CP组采用4℃UW溶液浸泡和冠脉灌注。FR-CP组采用4℃UW溶液，加入20 mg/L抗炎剂FR167653浸泡和冠脉灌注。结果表明，FR-CP组再灌注后血流动力学指标明显高于CP组（p<0.05），电镜观察显示，FR-CP组糖原保存较CP组好。使用我们的设备进行连续灌注和浸泡的联合保存方法，结合抑制促炎细胞因子，可改善移植后供者的心脏功能。研究2：我们以前曾报道过使用我科研制的仪器进行连续冠状动脉灌注法用于长期心脏保存的优越性。然而，心肌水肿是这种保存方法的问题之一。在本研究中，我们尝试对比研究12小时连续冠状动脉灌注和11小时简单浸泡后1小时冠状动脉灌注，以评估长期心脏保存的合适方法。本研究采用体重10-15kg的HBD犬。移植物分为两组；CP组（n=6）仅用4℃Celsior溶液连续冠脉灌注保存，SI+CP组（n=6）在用相同的溶液简单浸泡11小时后，再进行1小时冠脉灌注保存。两组患者Tx后血流动力学维持在基线水平的70-90%左右，两组之间HR、CO和E_<max>无显著差异。另一方面，SI+CP组心肌含水量显著低于CP组（p<0.05）。单纯浸泡保存后的短期冠状动脉灌注是满足长期心脏保存的一种可比较的方法。据报道，COX-2在缺血-再灌注损伤中起重要作用，心脏异体移植排斥反应中COX-2 mRNA和蛋白表达上调。FK3311是COX-2活化的抑制因子。本研究的目的是评估FK3311抑制COX-2在犬模型移植后减少缺血再灌注损伤和改善供心功能方面的有效性。使用成年杂种狗。5只狗在再灌注前静脉给予FK3311 (3 mg/kg)，对照组（n = 5）静脉给予载药。与对照组相比，经fk处理的狗的血流动力学恢复率显著提高（p < 0.05）。因此，长期保存后，抑制COX-2可改善移植心脏功能。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