The heterotopic heart transplantation in mice as a small animal model to study mechanical unloading - Establishment of the procedure, perioperative management and postoperative scoring

TY - JOUR

T1 - The heterotopic heart transplantation in mice as a small animal model to study mechanical unloading - Establishment of the procedure, perioperative management and postoperative scoring

AU - Westhofen, Sumi

AU - Jelinek, Marisa

AU - Dreher, Leonie

AU - Biermann, Daniel

AU - Martin, Jack

AU - Vitzthum, Helga

AU - Reichenspurner, Hermann

AU - Ehmke, Heimo

AU - Schwoerer, Alexander Peter

PY - 2019/4/12

Y1 - 2019/4/12

N2 - BACKGROUND: Unloading of failing hearts by left ventricular assist devices induces an extensive cardiac remodeling which may lead to a reversal of the initial phenotype-or to its deterioration. The mechanisms underlying these processes are unclear.HYPOTHESIS: Heterotopic heart transplantion (hHTX) is an accepted model for the study of mechanical unloading in rodents. The wide variety of genetically modified strains in mice provides an unique opportunity to examine remodeling pathways. However, the procedure is technically demanding and has not been extensively used in this area. To support investigators adopting this method, we present our experience establishing the abdominal hHTX in mice and describe refinements to the technique.METHODS: In this model, the transplanted heart is vascularised but implanted in series, and therefore does not contribute to systemic circulation and results in a complete mechanical unloading of the donor heart. Training followed a systematic program using a combination of literature, video tutorials, cadaveric training, direct observation and training in live animals.RESULTS: Successful transplantation was defined as a recipient surviving > 24 hours with a palpable, beating apex in the transplanted heart and was achieved after 20 transplants in live animals. A success rate of 90% was reached after 60 transplants. Operative time was shown to decrease in correlation with increasing number of procedures from 200 minutes to 45 minutes after 60 operations. Cold/warm ischemia time improved from 45/100 to 10/20 minutes. Key factors for success and trouble shootings were identified.CONCLUSION: Abdominal hHTX in the mouse may enable future examination of specific pathways in unloading induced myocardial remodeling. Establishment of the technique, however, is challenging. Structured training programs utilising a variety of training methods can help to expedite the process. Postoperative management, including daily scoring increases animal wellbeing and helps to predict survival.

AB - BACKGROUND: Unloading of failing hearts by left ventricular assist devices induces an extensive cardiac remodeling which may lead to a reversal of the initial phenotype-or to its deterioration. The mechanisms underlying these processes are unclear.HYPOTHESIS: Heterotopic heart transplantion (hHTX) is an accepted model for the study of mechanical unloading in rodents. The wide variety of genetically modified strains in mice provides an unique opportunity to examine remodeling pathways. However, the procedure is technically demanding and has not been extensively used in this area. To support investigators adopting this method, we present our experience establishing the abdominal hHTX in mice and describe refinements to the technique.METHODS: In this model, the transplanted heart is vascularised but implanted in series, and therefore does not contribute to systemic circulation and results in a complete mechanical unloading of the donor heart. Training followed a systematic program using a combination of literature, video tutorials, cadaveric training, direct observation and training in live animals.RESULTS: Successful transplantation was defined as a recipient surviving > 24 hours with a palpable, beating apex in the transplanted heart and was achieved after 20 transplants in live animals. A success rate of 90% was reached after 60 transplants. Operative time was shown to decrease in correlation with increasing number of procedures from 200 minutes to 45 minutes after 60 operations. Cold/warm ischemia time improved from 45/100 to 10/20 minutes. Key factors for success and trouble shootings were identified.CONCLUSION: Abdominal hHTX in the mouse may enable future examination of specific pathways in unloading induced myocardial remodeling. Establishment of the technique, however, is challenging. Structured training programs utilising a variety of training methods can help to expedite the process. Postoperative management, including daily scoring increases animal wellbeing and helps to predict survival.

U2 - 10.1371/journal.pone.0214513

DO - 10.1371/journal.pone.0214513

M3 - SCORING: Journal article

C2 - 30978185

VL - 14

SP - e0214513

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 4

ER -