Heterotopic heart transplantation in rats has been a commonly used model for diverse immunological studies for more than 50 years. Several modifications have been reported since the first description in 1964. After 30 years of performing heterotopic heart transplantation in rats, we have developed a simplified surgical approach, which can be easily taught and performed without further surgical training or background. After dissection of the ascending aorta and the pulmonary artery and ligation of superior and inferior caval and pulmonary veins, the donor heart is harvested and subsequently perfused with ice-cold saline solution supplemented with heparin. After clamping and incising the recipient abdominal vessels, the donor ascending aorta and pulmonary artery are anastomosed to the recipient abdominal aorta and inferior vena cava, respectively, using continuous running sutures. Depending on different donor-recipient combinations, this model allows analyses of either acute or chronic rejection of allografts. The immunological significance of this model is further enhanced by a novel approach of in-ear injection of vital cardiac muscle cells and subsequent analysis of draining cervical lymphatic tissue.
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http://dx.doi.org/10.3791/60956 | DOI Listing |
Transplantation
January 2025
Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Background: Long-term renal allograft acceptance has been achieved in macaques using a transient mixed hematopoetic chimerism protocol, but similar regimens have proven unsuccessful in heart allograft recipients unless a kidney transplant was performed simultaneously. Here, we test whether a modified protocol based on targeting CD154, CD2, and CD28 is sufficient to prolong heart allograft acceptance or promote the expansion of regulatory T cells.
Methods: Eight macaques underwent heterotopic allo-heart transplantation from major histocompatibility complex-mismatched donors.
Curr Cardiol Rep
January 2025
Department of Cardiovascular Medicine, Heart Vascular & Thoracic Institute, Cleveland Clinic, 9500 Euclid Avenue, J2-3, Cleveland, OH, 44195, USA.
Purpose Of Review: We describe the evolution of caval valve implantation (CAVI) as a treatment for severe symptomatic tricuspid regurgitation (TR) in the high surgical risk patient.
Recent Findings: Surgical treatment of severe TR is often limited by the high surgical risk of the patients who tend to develop severe secondary TR. Coaptation, annuloplasty, and orthotopic replacement strategies are all limited by annular and leaflet geometry, prior valve repair, and the presence of cardiac implantable device leads.
Commun Med (Lond)
January 2025
Department of Surgery, The University of Maryland School of Medicine, Baltimore, MD, USA.
Background: Improvement in gene modifications of donor pigs has led to the prevention of early cardiac xenograft rejection and significantly prolonged cardiac xenograft survival in both heterotopic and orthotopic preclinical non-human primate (NHP) models. This progress formed the basis for FDA approval for compassionate use transplants in two patients.
Methods: Based on our earlier report of 9-month survival of seven gene-edited (7-GE) hearts transplanted (life-supporting orthotopic) in baboons, we transplanted 10 gene-edited pig hearts into baboons (n = 4) using non-ischemic continuous perfusion preservation (NICP) and immunosuppression regimen based on co-stimulation blockade by anti-CD40 monoclonal antibody.
Front Transplant
December 2024
Duke Transplant Center, Duke University School of Medicine, Durham, NC, United States.
Objective: Cardiac Allograft Vasculopathy (CAV), a process of vascular damage accelerated by antibody-mediated rejection (AMR), is one of the leading causes of cardiac transplant failure. Proteasome inhibitors (PIs) are utilized to treat AMR, however PI-associated toxicity limits their therapeutic utility. Novel immunoproteasome inhibitors (IPIs) have higher specificity for immune cells and have not been investigated for AMR in cardiac transplant patients.
View Article and Find Full Text PDFEur J Heart Fail
November 2024
Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, Germany.
Aims: Right ventricular reverse remodelling (RVRR) is linked to improved survival in patients with severe tricuspid regurgitation (TR) and right-sided heart failure who underwent interventional treatment. However, the role of residual TR on RVRR remains unclear. In this analysis the impact of residual TR on RVRR after interventional TR treatment, which was validated by two independent cohorts at four sites using echocardiography or cardiac magnetic resonance (CMR) imaging, was investigated.
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