Abstract: TH-PO0139
Preexisting Heart Failure Exacerbates Renal Medullary Tissue Hypoxia Following Cardiopulmonary Bypass in Sheep
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Trask-Marino, Anton Lewis, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
- Marino, Bruno, Cellsaving and Perfusion Resources, Melbourne, Victoria, Australia
- Cochrane, Andrew Donald, Department of Cardiothoracic Surgery, Monash Health and Department of Surgery (School of Clinical Sciences at Monash Health), Monash University, Melbourne, Victoria, Australia
- McCall, Peter Richmond, Austin Hospital Department of Anaesthesia, Heidelberg, Victoria, Australia
- Raman, Jaishankar, Department of Cardiothoracic Surgery, St Vincent’s Hospital, The University of Melbourne, Melbourne, Victoria, Australia
- Furukawa, Taku, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
- Ow, Connie, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
- Booth, Lindsea C., The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
- May, Clive N., The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
- Lankadeva, Yugeesh Ryan, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
Background
Acute kidney injury (AKI) is a major unresolved complication of cardiac surgery, particularly in patients with pre-existing heart failure (HF). Progress has been limited by a lack of clinically relevant animal models to study the complex pathophysiology. We developed a novel large animal model of HF with continuous assessment of renal tissue perfusion and oxygenation before, during and after cardiopulmonary bypass (CPB).
Methods
Merino ewes (30-45 kg) were instrumented to measure cardiac output (CO), mean arterial pressure (MAP), renal blood flow (RBF), renal oxygen delivery (RDO2), and renal cortical and medullary tissue perfusion and oxygenation (PO2) across pre- (conscious), intra- (anesthetized) and post-CPB (conscious) phases. HF was induced via coronary artery ligation and defined by ≥30% reduction in left ventricular ejection fraction. HF (n=9) and healthy control (n=8) animals underwent 2 h of CPB with aortic cross clamp (pump flow 2.4 L/min/m2, target MAP ~70 mmHg), followed by 48-h recovery.
Results
CPB reduced RBF and RDO2 similarly in both groups (RBF: -56% HF, -55% control; RDO2: -64% HF, -68% control; all p<0.01). Renal medullary tissue perfusion and PO2 also fell during CPB (perfusion: HF -71%, p=0.02; control -56%, p=0.08; PO2: HF -42%, p=0.03; control -46%, p=0.5), with no significant group differences. However, by 48-h post-CPB, medullary PO2 recovered in controls but remained markedly reduced in HF animals (8.0±3.7 vs 30.6±5.5 mmHg, p=0.02), despite similar MAP, CO, RBF, and renal cortical perfusion and PO2 between groups. HF animals had a numerically higher incidence of postoperative AKI (55% vs 12.5%, OR 8.75). Across both groups, sheep that developed AKI had significantly lower postoperative medullary PO2 than those without AKI (18.7±3.5 vs 31.3±3.5 mmHg, p=0.04).
Conclusion
In a clinically relevant large mammalian model of CPB, perioperative renal medullary hypoxia was associated with AKI. Pre-existing HF exacerbated this hypoxia during recovery, despite normalization of systemic hemodynamics and renal cortical oxygenation. Renal medullary hypoxia may represent a novel therapeutic target to prevent AKI following cardiac surgery, particularly in patients with pre-existing heart failure.