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Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24\u00a0h of donor BSD.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>BSD donors (vs. sham neurological injury, 4\/group) were hemodynamically supported and monitored for 24\u00a0h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6\u00a0h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, <jats:italic>p<\/jats:italic>\u2009=\u20090.09), systemic inflammation (IL-6\u00a0-\u00a0<jats:italic>p<\/jats:italic>\u2009=\u20090.025, IL-8\u00a0-\u00a0<jats:italic>p<\/jats:italic>\u2009=\u20090.002) and cardiac injury (cardiac troponin I, <jats:italic>p<\/jats:italic>\u2009=\u20090.048), requiring vasopressor support (vasopressor dependency index, VDI, <jats:italic>p<\/jats:italic>\u2009=\u20090.023), with normalisation of biomarkers and physiology over 24\u00a0h. All hearts were weaned from CPB and monitored for 6\u00a0h post-HTx, except one (sham) recipient that died 2\u00a0h post-HTx. Hemodynamic (VDI\u00a0-\u00a0<jats:italic>p<\/jats:italic>\u2009=\u20090.592, heart rate\u00a0-\u00a0<jats:italic>p<\/jats:italic>\u2009=\u20090.747) and metabolic (blood lactate, <jats:italic>p<\/jats:italic>\u2009=\u20090.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We have successfully developed an ovine HTx model following 24\u00a0h of donor BSD. After 6\u00a0h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40635-021-00425-4","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:05:56Z","timestamp":1640304356000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A clinically relevant sheep model of orthotopic heart transplantation 24\u00a0h after donor brainstem death"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-205X","authenticated-orcid":false,"given":"Louise E.","family":"See Hoe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Wildi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nchafatso 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Animal studies were undertaken at the Queensland University of Technology (QUT) Medical Engineering Research Facility in Brisbane between March 2017 and December 2018. Animal ethics was approved by the QUT Animal Ethics Committee (AEC) (16000001109) and ratified by the University of Queensland AEC (QUT\/393\/17\/QUT). All experiments were performed in accordance with the National Health and Medical Research Council (NHMRC) Australian Code of Practice for the Care and Use of Animals for Scientific Purposes 8th Edition 2013 and the Animal Care and Protection Act 2001 (QLD) and complied with the ARRIVE Guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Outside of the submitted work, Professor Fraser receives reimbursement for travel costs and incidentals when presenting research he has performed in collaboration with Fisher and Paykel Healthcare. Professor Fraser is the co-founder and CEO of De Motu Cordis Pty Limited, and the Quantum Medical Innovation Fund. He is also the co-founder of BiVACOR\u2122 Pty Ltd. In addition, Prof. Fraser and his research group work with Fisher and Paykel healthcare, Mallinckrodt Pharmaceuticals, CSL, BiVACOR\u2122, De Motu Cordis Pty Limited, and Australian Red Cross Lifeblood. Professor McGiffin provides consultancy services to Abbott. Assoc Prof David Platts has acted as a clinical liaison with Philips Healthcare, GE Healthcare and Lantheus Medical Imaging. This has no direct impact on the contents of the manuscript. The other authors do not have any conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"60"}}