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Heterotopic vascularized murine cardiac transplantation to study graft arteriopathy

Abstract

The development of microsurgical techniques has facilitated the establishment of fully vascularized cardiac transplantation models in small mammals. A particularly useful model that has evolved for the study of cardiac allograft vasculopathy (CAV) is a heterotopic (abdominal) vascularized murine cardiac transplantation model. Using this model has permitted the elucidation of genetic, immune and non-immune factors contributing to the development of this inexorable pathological condition, which compromises half of all human cardiac transplants. This protocol details methods for performing the transplant, histomorphometric assessment of the graft vasculature and functional evaluation of the transplanted heart. In experienced hands, the surgical procedure requires approximately 75 min to complete, and vasculopathy results are obtained at 2 months. This model entails a fully vascularized implantation technique in which the donor ascending aorta and pulmonary artery are sutured end-to-side to the recipient abdominal aorta and inferior vena cava, respectively. As this model reliably reproduces immunological and non-immunological features of CAV, investigators can thoroughly explore contributory mechanisms, diagnostic modalities and therapeutic approaches to its mitigation.

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Figure 1
Figure 2: Echocardiographic assessment of cardiac graft function, performed on a transplanted mouse heart using a 30-mHz transducer.
Figure 3: Sample histomorphometric tracing for determination of CAV.
Figure 4: Representative histology of cardiac allograft vasculopathy (CAV).

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Acknowledgements

This work was supported in part by National Institutes of Health grants HL55397 and HL085149, as well as the Scleroderma Research Foundation.

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Correspondence to David J Pinsky.

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Hasegawa, T., Visovatti, S., Hyman, M. et al. Heterotopic vascularized murine cardiac transplantation to study graft arteriopathy. Nat Protoc 2, 471–480 (2007). https://doi.org/10.1038/nprot.2007.48

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