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.

Interleukin-6 Receptor Signaling Disruption Prevents Cardiac Allograft Deterioration in Mice

“…23,24 Immune responses against grafts that ultimately result in chronic rejection can be studied in a mouse vascularized heterotopic cardiac transplant model. [12][13][14] Our investigation indicates that IL-6 receptor signaling blockade down-regulated activation of peripheral T cells. In the high-dose MR16-1-alone regimen, activation level of CD4+ and CD8+ T cells was down-regulated 7 days after transplant; however, activation levels became equivalent to those of the untreated controls 14 days after transplant (data not shown).…”

“…[12][13][14] Afanasyeva and associates 15 stated that IL-6 plays a crucial role in cardiac hypertrophy and fibrosis associated with chronic rejection. These results suggest IL-6 as a target for treating graft rejection by protecting the grafted organ from chronic inflammation.…”

Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection

“…Specific protocols were approved by the local Institutional Animal Care and Use Committee. Donor hearts from wild-type and cardiacspecific GTPCH transgenic mice on a C57BL/6 background (H-2 b ) were transplanted heterotopically to BALB/c (H-2 d ) recipient mice as described (6) with the modification that excised donor hearts were placed in Aedesta organ and tissue medium (Cell Preservations Solutions, Columbia, SC).…”

Potential of Heterotopic Cardiac Transplantation in Mice as a Model for Elucidating Mechanisms of Graft Rejection

“…The model of heterotopic heart transplantation in mice has been varied manifoldly since its first description by Robert Corry and Paul S. Russell in 1973 [Mao et al, 2009;Wang et al, 2005;Hasegawa et al, 2007]. The following chapter describes the transplantation procedure and incorporates our experience using an operating microscope (OPMI-6, Carl Zeiss, Jena, Germany) and a magnification between 4x-20x objective.…”