Background: Allograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft rejection. Therefore, we developed a combined abdominal heart and aorta transplantation model in mice which benefits from reducing animal and drug utilization, while providing an improved model to study the progressive nature of AV. Methods: The middle of the infrarenal aorta of the recipient mouse was ligatured between the renal artery and its bifurcation. Proximal and distal aortotomies were performed at this site above and below the ligature, respectively, for the subsequent anastomoses of the donor aorta and heart grafts to the recipient infrarenal aorta in an end-to-side fashion. The distal anastomotic site of the recipient infrarenal aorta was connected with the outlet of the donor aorta. Uniquely, the proximal anastomotic site on the recipient infrarenal aorta was shared to connect with both the inlet of the donor aorta and the inflow tract to the donor heart. The outflow tract from the donor heart was connected to the recipient inferior vena cava (IVC). Results: The median times for harvesting the heart graft, aorta graft, recipient preparation and anastomosis were 11.5, 8.0, 9.0 and 40.5 min, respectively, resulting in a total median ischemic time of 70 min. The surgery survival rate was more than 96% (29/30). Both the syngeneic C57Bl/6 aorta and heart grafts survived more than 90 days in 29 C57Bl/6 recipients. Further, Balb/c to C57Bl/6 allografts treated with anti-CD40L and CTLA4.Ig survived more than 90 days with a 100% (3/3) survival rate. (3/3). Conclusions: This model is presented as a new tool for researchers to investigate transplant immunology and assess immunosuppressive strategies. It is possible to share a common anastomotic stoma on the recipient abdominal aorta to reconstruct both the aorta graft entrance and heart graft inflow tract. This allows for the study of allogeneic effects on both the aorta and heart from the same animal in a single survival surgery.

中文翻译：

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小鼠腹部异位心脏和主动脉联合移植模型

背景：同种异体血管病变（AV）仍然是同种异体移植长期生存的主要障碍。尽管已经证明小鼠主动脉移植模型是研究AV发病机理的有用工具，但同时进行主动脉移植和另一器官移植可能揭示了更多与临床相关的机制，这些机制有助于慢性同种异体移植排斥反应的发生。因此，我们开发了一种结合了小鼠腹部和主动脉的移植模型，该模型受益于减少动物和药物的使用，同时提供了一种改进的模型来研究AV的进行性。方法：将受体小鼠的肾下主动脉中部结扎在肾动脉及其分支之间。在结扎上方和下方的这个部位进行近端和远端主动脉切开术，分别以端到端方式将供体主动脉和心脏移植物随后移植到受体肾下主动脉。受体肾下主动脉的远端吻合部位与供体主动脉的出口相连。独特的是，接受者肾下主动脉上的近端吻合部位被共享，以与供体主动脉的入口和供体心脏的流入通道连接。来自供体心脏的流出道与受体下腔静脉（IVC）连接。结果：收获心脏移植物，主动脉移植物，受体准备物和吻合术的中位时间分别为11.5、8.0、9.0和40.5分钟，因此总中位缺血时间为70分钟。手术存活率超过96％（29/30）。同种C57Bl / 6主动脉和心脏移植物在29名C57Bl / 6受体中存活了90天以上。此外，用抗CD40L和CTLA4.Ig治疗的Balb / c至C57Bl / 6同种异体移植物存活超过90天，存活率为100％（3/3）。（3/3）。结论：该模型是研究人员研究移植免疫学和评估免疫抑制策略的新工具。可以在接受者腹主动脉上共享一个普通的吻合口，以重建主动脉移植物入口和心脏移植物流入通道。这允许在一次生存手术中研究同一只动物对主动脉和心脏的同种异体效应。结论：该模型是研究人员研究移植免疫学和评估免疫抑制策略的新工具。可以在接受者腹主动脉上共享一个普通的吻合口，以重建主动脉移植物入口和心脏移植物流入通道。这允许在一次生存手术中研究同一只动物对主动脉和心脏的同种异体效应。结论：该模型是研究人员研究移植免疫学和评估免疫抑制策略的新工具。可以在接受者腹主动脉上共享一个普通的吻合口，以重建主动脉移植物入口和心脏移植物流入通道。这允许在一次生存手术中研究同一只动物对主动脉和心脏的同种异体效应。