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Abstract
Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.
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1 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); St Andrews War Memorial Hospital, Intensive Care Unit, Brisbane, Australia (GRID:grid.1003.2); North Estonia Medical Centre, Department of Intensive Care, Tallinn, Estonia (GRID:grid.454953.a) (ISNI:0000 0004 0631 377X)
2 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); Korea University, Department of Thoracic and Cardiovascular Surgery, College of Medicine, Seoul, Republic of Korea (GRID:grid.222754.4) (ISNI:0000 0001 0840 2678)
3 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy (GRID:grid.4708.b) (ISNI:0000 0004 1757 2822)
4 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); Sorbonne Université, Assistance Publique des Hôpitaux de Paris (AP-HP), Medical ICU, Pitié-Salpêtrière University Hospital, INSERM UMRS-1166, Paris, France (GRID:grid.411439.a) (ISNI:0000 0001 2150 9058)
5 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537)
6 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); North Estonia Medical Centre, Department of Intensive Care, Tallinn, Estonia (GRID:grid.454953.a) (ISNI:0000 0004 0631 377X)
7 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266)
8 Australian Red Cross Lifeblood, Research and Development, Sydney, Australia (GRID:grid.420118.e) (ISNI:0000 0000 8831 6915); University of Sydney, Faculty of Medicine and Health, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X)
9 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); Queensland University of Technology, Science and Engineering Faculty, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953)
10 The University of Queensland, School of Veterinary Science, Gatton, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537)
11 University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537)
12 North Estonia Medical Centre, Department of Intensive Care, Tallinn, Estonia (GRID:grid.454953.a) (ISNI:0000 0004 0631 377X)
13 Maastricht University Medical Centre, Cardio-Thoracic Surgery Department, Maastricht, The Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
14 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); St Andrews War Memorial Hospital, Intensive Care Unit, Brisbane, Australia (GRID:grid.1003.2); Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (GRID:grid.10403.36); Wesley Medical Research, Brisbane, Australia (GRID:grid.431722.1)
15 The Prince Charles Hospital, Critical Care Research Group, Brisbane, Australia (GRID:grid.415184.d) (ISNI:0000 0004 0614 0266); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); St Andrews War Memorial Hospital, Intensive Care Unit, Brisbane, Australia (GRID:grid.1003.2); Wesley Medical Research, Brisbane, Australia (GRID:grid.431722.1)