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Heart Transplantation From Brain Dead Donors: A Systematic Review of Animal Models
Louise E See Hoe1,2, Matthew A Wells1,3, Nicole Bartnikowski1,4
1Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.
Insights
Animal models of brain death and heart transplantation (HTx) show significant heterogeneity, hindering clinical translation. Further research is needed to improve donor heart quality and transplant outcomes.
Area of Science:
- Cardiology
- Transplantation Immunology
- Surgical Research
Background:
- Heart transplantation (HTx) is the optimal treatment for end-stage heart failure, but donor heart availability is limited.
- Donor hearts from brain-dead individuals face pathophysiological challenges impacting transplant success.
- Primary graft dysfunction remains a significant cause of mortality post-cardiac transplantation.
Purpose of the Study:
- To systematically review animal models of brain death followed by heart transplantation.
- To assess the scientific rigor and clinical relevance of existing animal models.
- To identify translational challenges hindering advancements in heart transplantation research.
Main Methods:
- Systematic literature review of animal models incorporating donor brain death and HTx.
- Screening of studies using MEDLINE and Embase databases.
- Assessment of 29 selected studies for rigor and clinical relevance.
Main Results:
- Identified marked heterogeneity in animal models of donor brain death and HTx.
- Few research groups globally utilize these specific models.
- Reporting on transplant success determinants was mixed; post-transplant function assessment was limited to invasive methods.
Conclusions:
- Existing animal models for brain death and HTx exhibit significant heterogeneity and limited clinical relevance.
- Translational challenges between animal models and clinical practice impede progress in heart transplantation research.
- Standardization and improved reporting in animal models are crucial for advancing the field.
Abstract:
Despite advances in mechanical circulatory devices and pharmacologic therapies, heart transplantation (HTx) is the definitive and most effective therapy for an important proportion of qualifying patients with end-stage heart failure. However, the demand for donor hearts significantly outweighs the supply. Hearts are sourced from donors following brain death, which exposes donor hearts to substantial pathophysiological perturbations that can influence heart transplant success and recipient survival. Although significant advances in recipient selection, donor and HTx recipient management, immunosuppression, and pretransplant mechanical circulatory support have been achieved, primary graft dysfunction after cardiac transplantation continues to be an important cause of morbidity and mortality. Animal models, when appropriate, can guide/inform medical practice, and fill gaps in knowledge that are unattainable in clinical settings. Consequently, we performed a systematic review of existing animal models that incorporate donor brain death and subsequent HTx and assessed studies for scientific rigor and clinical relevance. Following literature screening via the U.S National Library of Medicine bibliographic database (MEDLINE) and Embase, 29 studies were assessed. Analysis of included studies identified marked heterogeneity in animal models of donor brain death coupled to HTx, with few research groups worldwide identified as utilizing these models. General reporting of important determinants of heart transplant success was mixed, and assessment of posttransplant cardiac function was limited to an invasive technique (pressure-volume analysis), which is limitedly applied in clinical settings. This review highlights translational challenges between available animal models and clinical heart transplant settings that are potentially hindering advancement of this field of investigation.
