Morbidity and Mortality of Heterotopic Partial Heart Transplantation in Rodent Models

Abstract

Unrepairable congenital heart valve disease is an unsolved problem in pediatric cardiac surgery because there are no growing heart valve implants. Partial heart transplantation is a new type of transplant that aims to solve this problem. In order to study the unique transplant biology of partial heart transplantation, animal models are necessary. This study aimed to assess the morbidity and mortality of heterotopic partial heart transplantation in rodent models. This study assessed two models. The first model involved transplanting heart valves from donor animals into the abdominal aortic position in the recipient animals. The second model involved transplanting heart valve leaflets into the renal subcapsular position of the recipient animals. A total of 33 animals underwent heterotopic partial heart transplantation in the abdominal aortic position. The results of this model found a 60.61% (n = 20/33) intraoperative mortality rate and a 39.39% (n = 13/33) perioperative mortality rate. Intraoperative mortality was due to vascular complications from the procedure, and perioperative mortality was due to graft thrombosis. A total of 33 animals underwent heterotopic partial heart transplantation in the renal subcapsular position. The results of this model found a 3.03% (n = 1/33) intraoperative mortality rate, and the remaining 96.97% survived (n = 32/33). We conclude that the renal subcapsular model has a lower mortality rate and is technically more accessible than the abdominal aortic model. While the heterotopic transplantation of valves into the abdominal aortic position had significant morbidity and mortality in the rodent model, the renal subcapsular model provided evidence for successful heterotopic transplantation.

Animal models for partial heart transplantation

“…21 This results in abnormal blood flow patterns and removes the pressure gradient necessary to open and close the donor valve. 22 In order to avoid size mismatch of the anastomoses during implantation, Lee et al developed a rodent model where a donor pulmonary valve is transplanted orthotopically into a second donor heart. The caval veins and pulmonary veins of this donor heart are ligated.…”

“…In every case, the mode of death was either graft thrombosis or bleeding. 22 Similarly, Niimi et al required 78 operations to achieve a 90% success rate. 24 Therefore, heterotopic partial heart transplantation in the abdominal aorta is most appropriate for research teams with a skilled microsurgeon.…”

Partial heart transplantation: Growing heart valve implants for children

“…We started our research program with in vitro experiments 52 and rodent heterotopic partial heart transplantation experiments. 57 However, the rodent heterotopic partial heart transplant experiments failed miserably, presumably because a second valve transplanted in series with the native aortic valve does not experience sufficient pressure differentials to open and close physiologically. Additional funding subsequently allowed us to perform experimental open-heart surgery to replace the pulmonary valve with partial heart transplants in piglets (Figure 4).…”

“…This has important clinical implications for optimal preservation strategies and optimal levels of recipient immunosuppression. To study these questions, further investigations in vitro 52 and in vivo involving small 57,81 and large 82,83 animal models will be necessary.…”

Semilunar valve growth and function 10 years after infant heart transplantation: Predicting long‐term outcomes of partial heart transplants

“…This allows P-HTs to grow with the recipient. Short-term outcomes of P-HT were evaluated in piglets for months 2,3 and in the first human patients for 1 year. 4 However, the long-term outcomes of P-HT are unknown.…”