The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease

Abstract

The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent's Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170-180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.

Keywords: Healthy donor human hearts; Human heart failure; Human heart tissue bank; Reducing the use of animals in research.

Fig. 1

A visual representation of researchers from laboratories around the world that have collaborated with the Sydney Heart Bank

Fig. 2

This image was copied (with permission) from the Human Protein Atlas (HPA) website (proteinaltas.org). It shows the immunohistochemical identification of the HPA antibody, HPA019497) with the intercalated discs of healthy donor human left ventricle

Fig. 3

The above discussion implies that the scientific output by the Sydney Heart Bank should increase as both the number of collaborators grew. This figure shows that both the number of publications and the number of citations increased during the past decade. The data were derived from the Web of Science

Fig. 4

This schematic flow chart shows the connections between the Sydney Heart Bank (blue) and seven classes of heart failure using statistically significant numbers of patient types (brown), where specific cell types or whole tissue was involved (red), and where the type of investigations (green) involved sarcomeric, cytoplasmic proteins, or cardiomyocyte membranes (blue) that resulted in publications based on the topics listed (purple). The papers arising and their citations are detailed in Fig. 3