Heterotopic Heart Transplantation In Mice To Study Mechanical Unloading
Sumi Westhofen1, Alexander Schwoerer2, Marisa Jelinek2, Daniel Biermann1, Hermann Reichenspurner1, Heimo Ehmke2.
1University Heart Center Hamburg, Hamburg, Germany, 2University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Unloading of failing hearts by left ventricular (LV) assist devices can impair LV function, thus increasing mortality and morbidity. To clarify mechanisms underlying the detrimental effects on cardiac myocyte physiology, the heterotopic heart transplantation (hHTX) in transgenic mice would be an adequate animal model. Since the procedure is technically highly demanding with a low error tolerance it is hardly used. We present our experience establishing the hHTX in mice and first results.
Initial technical training was performed using video-education, rat hHTX that is well-established in our institution, and training in two institutes that successfully established the method in mice. “One-mouse-training-transplantations” were initially performed in dead mice, transplanting the orthotopic heart into the abdomen of the same animal. When technical confidence was reached, transplantation of a donor heart from one mouse to the abdomen of a syngeneic recipient (“two-mouse-transplantation”) was performed (FVB, age 7-10 weeks).
20 “one-mouse-training-operations” were performed. Operation time and cold/warm ischemia times decreased significantly with the procedures. The first successful transplantation with a well-beating graft and a survival of the recipient > 24hours was achieved after 20 “two-mouse-transplantations”. A first success rate of 90% was reached after 60 “two-mouse-transplantations” with further operations needed to stabilize this success. Despite a large heterogeneity in response to unloading, 14 days of unloading induced a significant weight reduction of the graft compared to before implantation and to orthotopic hearts of the recipient animals. Key factors for success included renunciation of cardioplegia, continuous topical cooling of the donor heart, de-airing of anastomosis, loose suture of venous anastomosis, avoidance of torsion of the donor heart and recipient intestine.
We could successfully establish the hHTX in mice which resulted e.g. in a significant reduction of LV weight proofing an effective LV unloading. Learning hHTX in mice is laborious, time-consuming and costly. It can be improved considerably by sharing expertise and a structured educational programme. To avoid incorrect results each transplant has to be examined individually with caution to secondary processes, i.e. valvular leakage, which is underlining the complexity of this procedure.
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