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

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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