Heart Transplantation With Donation After Circulatory Death

Abstract

Heart transplantation remains the preferred option for improving quality of life and survival for patients suffering from end-stage heart failure. Unfortunately, insufficient supply of cardiac grafts has become an obstacle. Increasing organ availability with donation after circulatory death (DCD) may be a promising option to overcome the organ shortage. Unlike conventional donation after brain death, DCD organs undergo a period of warm, global ischemia between circulatory arrest and graft procurement, which raises concerns for graft quality. Nonetheless, the potential of DCD heart transplantation is being reconsidered, after reports of more than 70 cases in Australia and the United Kingdom over the past 3 years. Ensuring optimal patient outcomes and generalized adoption of DCD in heart transplantation, however, requires further development of clinical protocols, which in turn require a better understanding of cardiac ischemia-reperfusion injury and the various possibilities to limit its adverse effects. Thus, we aim to provide an overview of the knowledge obtained with preclinical studies in animal models of DCD heart transplantation, to facilitate and promote the most effective and efficient advancement in preclinical research. A literature search of the PubMed database was performed to identify all relevant preclinical studies in DCD heart transplantation. Specific aspects relevant for DCD heart transplantation were analyzed, including animal models, graft procurement and storage conditions, cardioprotective approaches, and graft evaluation strategies. Several potential therapeutic strategies for optimizing graft quality are identified, and recommendations for further preclinical research are provided.

A Novel Rat Model of Cardiac Donation After Circulatory Death Combined With Normothermic ex situ Heart Perfusion

“…Compared with exsanguination, an entire circulatory load is unavoidable for the DCD hearts during hypoxia caused by asphyxiation (30). Besides, hypoxic pulmonary vasoconstriction following asphyxiation results in right ventricular dilatation and more damage to hearts compared with exsanguination (3,31). To induce asphyxiation, Quader et al terminated the ventilation support following paralyzing skeletal muscles with muscle relaxants (32,33), while Tolboom et al chose to transect the diaphragm (12,13).…”

“…Aceros et al and Kearns et al declared circulatory death and initiation of warm ischemia when asystole or systolic blood pressure below 30 mmHg was observed (14,(16)(17)(18). Niederberger et al suggested that a clear definition of circulatory arrest and the timing of warm ischemia was significant because damage for the grafts before procurement might vary dramatically according to the different definitions of the warm ischemia start time (3).…”

“…However, DCD hearts inevitably suffer from myocardial injury following an obligatory warm ischemia time (from when the systolic blood pressure is lower than 50 mmHg after the withdrawal of life-sustaining therapy to reperfusion or cardioplegia) (3,4). Furthermore, few cardioprotective therapies are allowed to apply in donors before circulatory death due to the ethical and legal issue (1,3,5,6), and it's difficult to perform a proper functional assessment of a DCD heart before HTx (7).…”

“…Before its efficient clinical translation, pre-clinical animal models of ESHP are essential to address some key issues, including ideal perfusion pressure, priming solution, and appropriate hematocrit, as well as efficacy and optimal dose of novel post-conditioning agents added into perfusion circuit (9,10). Niederberger et al suggested that pigs or rats appeared to be preferable for the pre-clinical model of DCD hearts, concerning clinically relevant ischemic tolerance (3). Although evolving as an ideal model to perform basic and translational researches about ESHP (11), the porcine model of ESHP has the obvious disadvantages of being costly and labor-intensive.…”

Cellular and Molecular Mechanism of Cardiac Regeneration: A Comparison of Newts, Zebrafish, and Mammals

“…The only curative therapy for end-stage heart failure is heart transplantation. However, it is an invasive procedure and the demand greatly exceeds the limited number of donor hearts available [ 3 ].…”