Simplified Mouse Cervical Heart Transplantation Using a Cuff Technique

Objectives: Interleukin-6, a pleiotropic cytokine that functions in both innate and adaptive immune responses, has been implicated in allograft rejection. We analyzed the efficacy of anti interleukin-6 receptor monoclonal antibody in delaying allograft rejection in a murine model of a heart. Materials and Methods: To investigate the role of interleukin-6 receptor signal transduction in acute and chronic allograft rejection, we blocked interleukin-6 receptor signaling to suppress the alloimmune response in C57BL/6 recipients of BALB/c cardiac allografts. Results: Administration of a high-dose α-interleukin-6 receptor monoclonal antibody prevented the intragraft infiltration of inflammatory cells and lymphocytes and prolonged allograft survival during the peritransplant period. However, all allografts were rejected by 23.5 days after transplant. In contrast, cardiac allograft recipients treated with a cytotoxic T-lymphocyte antigen 4-immunoglobulin plus continued administration of low-dose α-interleukin-6 receptor monoclonal antibody showed long-term graft survival compared with cytotoxic T-lymphocyte antigen 4-immunoglobulin monotherapy. A histologic analysis revealed that graft fibrosis was prevented in cytotoxic T-lymphocyte antigen 4-immunoglobulin plus highdose α-interleukin-6 receptor monoclonal antibody group, but not in the cytotoxic T-lymphocyte antigen 4-immunoglobulin alone group. This suggests that deterioration of graft function associated with chronic rejection could be prevented by blocking interleukin-6 receptor signaling. Conclusions: Disruption of interleukin-6 receptor signaling is an effective strategy for modulating proinflammatory immune responses and preventing chronic rejection.

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“…16 Graft survival was monitored daily by palpation. Rejection was defined as a loss of palpable cardiac contractions.…”

Section: Vascularized Cervical Heart Transplantmentioning

confidence: 99%

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

Iida¹,

Omoto²,

Kanemitsu³

et al. 2012

Exp Clin Transplant

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“…The experimental transplantation setting we used herein is an established heterotopic cervical cardiac transplantation model using a cuff technique in rodents [11,12] . This offers an easily applicable transplantation model with excellent access to the transplanted graft for IVM [12,19,21] .…”

Section: Discussionmentioning

confidence: 99%

“…Heterotopic heart transplantation to the cervical vessels was performed as previously described [11] . Briefly, in Lewis rats (recipients), the right jugular vein and common carotid artery were dissected free through a right paramedian incision at the ventral aspect of the neck.…”

Section: Heterotopic Cardiac Xenotransplantationmentioning

confidence: 99%

The coronary microcirculation in hamster-to-rat cardiac xenografts

Buchholz¹,

Geiger²,

Michel³

et al. 2013

Thorac cardiovasc Surg

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Background:The aim of this study was to establish a new experimental model to directly analyse the coronary microcirculation in cardiac xenografts. Methods: Intravital fluorescence microscopy (IVM) of the subepicardial microcirculation in heterotopically transplanted hamster-to-rat cardiac xenografts was performed at 30 and 90 min of reperfusion. We quantitatively assessed the microcirculatory perfusion characteristics as well as the interactions of leukocytes and platelets with the endothelium of postcapillary coronary venules in non-sensitised as well as sensitised recipients. Results: In this first experimental IVM study of cardiac xenografts, we successfully visualised the subepicardial microcirculation, i.e. feeding arterioles, nutritive capillaries and draining postcapillary venules, during reperfusion. Leukocyteendothelial and platelet-endothelial cell interactions could be quantified. In the non-sensitised group, the myocardial microcirculation remained stable during the observation period of 90 min, whereas in the sensitised group, xenografts were rejected immediately. Conclusions: We established a model for the assessment of the microcirculatory dysfunction and inflammation during ischaemia/reperfusion injury in hamster-to-rat cardiac xenografts.

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“…Heterotopic heart transplant in the cervical area has been recognized as an alternative technique, often meeting a need for testing third-party heart transplant survival in mice that have already undergone abdominal heart transplant. To reduce the surgical difficulties of the cervical procedure, the common carotid artery and external jugular vein of the recipients are usually cut and cuffed for subsequent reconstruction of blood flow [6][7][8][9][10] ; however, this procedure alters hemodynamics and disrupts blood supply to the central nervous system, creating high blood pressure in the transplanted graft. Moreover, the cuff technique has a notable pitfall of thrombosis, 11 which affects long-term graft survival.…”

Section: Savithri Balasubramanianmentioning

confidence: 99%

Introduction of Modified Cervical Cardiac Transplant Model in Mice

Gong¹,

Thornley²,

Whitcher³

et al. 2012

Exp Clin Transplant

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Objectives: The murine cervical heterotopic heart transplant model was initially designed to test the immune response to third-party allografts, modified by cuff techniques. While cuff techniques simplify the execution of this procedure, cutting of the carotid artery and the external jugular vein alters the blood supply to central nervous system and makes it difficult to achieve long-term graft survival. In the present study, we describe modified techniques that preserve the continuity and function of blood vessels and improve transplant integrity. Materials and Methods:The modified techniques in this study comprise the following aspects: (1) Preservation of the sternal head of the right sternocleidomastoid muscle, (2) use of the donor's intrathoracic inferior vena cava for anastomosis and (3) preservation of the function of the recipient's carotid artery and external jugular vein and thus, continuity of blood flow to the central nervous system. Results: Stable, long-term, disease-free allograft survival has been achieved with syngeneic transplants (> 200 days), whereas allografts from fully major histocompatibility complex-mismatched donors were acutely rejected in a time similar to the traditional abdominal heterotopic heart transplant model (8.2 ± 1.3 vs 8.4 ± 1.4 days; P = .73 in the Mantel Cox test, and P = .61 in the Gehan-BreslowWilcoxon test). Similar alloresponses could be induced in these 2 models. Conclusions: It is possible and feasible to achieve long-term graft survival in the mouse cervical heart transplant model using the modified procedures described in the present study.

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Simplified Mouse Cervical Heart Transplantation Using a Cuff Technique

Cited by 112 publications

References 0 publications

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

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

The coronary microcirculation in hamster-to-rat cardiac xenografts

Introduction of Modified Cervical Cardiac Transplant Model in Mice

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