A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.

Autor:	See Hoe LE; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia. l.seehoe@uq.edu.au.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia. l.seehoe@uq.edu.au.; School of Pharmacy and Medical Sciences, Griffith University, Southport, QLD, Australia. l.seehoe@uq.edu.au., Wildi K; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Cardiovascular Research Institute Basel, Basel, Switzerland., Obonyo NG; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Wellcome Trust Centre for Global Health Research, Imperial College London, London, UK.; Initiative to Develop African Research Leaders (IDeAL), Kilifi, Kenya., Bartnikowski N; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology, Brisbane, QLD, Australia., McDonald C; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Department of Anaesthesia and Perfusion, The Prince Charles Hospital, Chermside, QLD, Australia., Sato K; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Heinsar S; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Second Department of Intensive Care, North Estonia Medical Centre, Tallinn, Estonia., Engkilde-Pedersen S; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Research and Development, Australian Red Cross Lifeblood, Brisbane, QLD, Australia., Diab S; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Passmore MR; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Wells MA; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; School of Pharmacy and Medical Sciences, Griffith University, Southport, QLD, Australia., Boon AC; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Esguerra A; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Research and Development, Australian Red Cross Lifeblood, Brisbane, QLD, Australia., Platts DG; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., James L; Department of Cardiac Surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia., Bouquet M; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Hyslop K; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Shuker T; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Ainola C; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Colombo SM; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Department of Pathophysiology and Transplantation, Università Degli Studi di Milano, Milan, Italy., Wilson ES; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Millar JE; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Roslin Institute, University of Edinburgh, Edinburgh, UK., Malfertheiner MV; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Department of Internal Medicine II, Cardiology and Pneumology, University Medical Center Regensburg, Regensburg, Germany., Reid JD; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., O'Neill H; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Livingstone S; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Abbate G; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., Sato N; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., He T; Department of Cardiac Surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia., von Bahr V; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden., Rozencwajg S; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Pitié-Salpêtrière University Hospital, Paris, France., Byrne L; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; The Canberra Hospital Intensive Care, Garran, ACT, Australia.; Australia National University, Canberra, ACT, Australia., Pimenta LP; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia., Marshall L; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Department of Cardiac Surgery, Princess Alexandra Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital, Brisbane, QLD, Australia., Nair L; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital, Brisbane, QLD, Australia., Tung JP; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Research and Development, Australian Red Cross Lifeblood, Brisbane, QLD, Australia.; Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia., Chan J; Prince Charles Hospital, Brisbane, QLD, Australia.; School of Medicine, Griffith University, Southport, QLD, Australia., Haqqani H; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Prince Charles Hospital, Brisbane, QLD, Australia., Molenaar P; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia., Li Bassi G; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain., Suen JY; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia., McGiffin DC; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Cardiothoracic Surgery and Transplantation, The Alfred Hospital, Melbourne, VIC, Australia.; Monash University, Melbourne, VIC, Australia., Fraser JF; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, Australia.; Prince Charles Hospital Northside Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Intensive care medicine experimental [Intensive Care Med Exp] 2021 Dec 24; Vol. 9 (1), pp. 60. Date of Electronic Publication: 2021 Dec 24.
DOI:	10.1186/s40635-021-00425-4
Abstrakt:	Background: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. 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 h of donor BSD. Methods: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, 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 h. 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. Results: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) 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. Conclusions: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h 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. (© 2021. The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.