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Images and Case Reports in Heart Failure

MRI of a Novel Murine Working Heart Transplant Model

Jose-Luiz Figueiredo, MD^*; Matthias Nahrendorf, MD, PhD^*; David E. Sosnovik, MD and Ralph Weissleder, MD, PhD

From the Center for Systems Biology (J.L.F., M.N., R.W.), Massachusetts General Hospital and Harvard Medical School, Simches Research Building, Boston, Mass; Center for Molecular Imaging Research (J.L.F., M.N., D.E.S., R.W.), Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass; and Cardiology Division (D.E.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Matthias Nahrendorf, MD, PhD, MGH-CSB, CPZN-5206, 185 Cambridge St, Boston, MA 02124. E-mail mnahrendorf@mgh.harvard.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Heart transplant recipients require frequent invasive endomyocardial biopsies, which carry a significant risk of complication and are prone to sampling errors. Although newer immunosuppressive therapies continue to improve survival rates, organ rejection still occurs and close surveillance of the graft is mandatory. There is, thus, a compelling need to develop (1) better immunosuppressive and tolerogenic strategies and (2) noninvasive, more predictive, and quantitative diagnostic tools to monitor individual patients and to test new treatment regimens in animal models and patient cohorts. Targeted molecular imaging approaches offer the potential for more sensitive early detection of transplant rejection.^1–4 Such emerging strategies, however, have to be validated in murine models that resemble rejection of the working human heart.

The retrogradely perfused, beating but nonworking heterotopic heart transplant model in the mouse has been extensively used in more than 30 years of research to address basic immunologic questions of rejection and tolerance because the mouse is the preferred species for basic immunology research. To our knowledge, to date, there have been no reports on working heart mouse models. The nonworking murine model has several physiologic limitations, because there is no forward flow through the grafted heart resulting from anastomosis of the donor aorta to the recipient aorta and the donor superior vena cava to the recipient inferior vena cava (IVC). Imaging studies as well as research into new immunosuppressive strategies would greatly benefit from a more realistic murine model with blood flow and cardiac workload conditions closer to human orthotopic transplantation. Orthotopic transplantation is . . . [Full Text of this Article]