Thoraco-Abdominale Normotherme Regionale Perfusie en Hartdonatie na Circulatoire Dood
Year: 2025
Type: dissertation
Abstract: Heart transplantation remains the gold standard for treating end-stage heart failure, but its application is limited by a shortage of donation after brain death donor hearts. The use of donation after circulatory death (DCD) organs is an option to alleviate this shortage, yet the inevitable warm ischemia incurred by these hearts compromises their viability. Thoraco-abdominal normothermic regional perfusion (TA-NRP) is a novel technique that restores warm, oxygenated blood flow to organs in situ after death declaration, mitigating ischemic injury and enabling functional assessment, which is particularly critical for the metabolically active heart. This research aimed to develop both preclinical and clinical TA-NRP programs to deepen our understanding of this technique, evaluate its effects on the thoracic organs, investigate the impact of technique modifications, and ultimately expand the clinical donor pool for heart transplantation. We first established a reproducible DCD TA-NRP porcine model yielding adequately functioning hearts. Using this model, we investigated whether the addition of a hemoadsorption filter in the extracorporeal circuit could reduce ischemia-induced inflammation. However, no significant differences were observed in cytokine levels, cardiac function, or hemodynamic parameters. Clinically, we designed and implemented a single-center multidisciplinary TA-NRP protocol, informed by our preclinical work and collaborations with experienced centers. Key elements included pre-procedural CT angiography, pre-mortem guidewire placement, right ventricular drainage before TA-NRP initiation, and static cold storage for heart preservation during transportation from a different center. Initial cases demonstrated successful implementation and favorable transplant outcomes. In response to ethical concerns about potential cerebral reperfusion during TA-NRP, we proposed protocol modifications involving initial isolated perfusion of the vented heart and abdomen. This allowed time for ligation and distal cannulation of the supra-aortic vessels to enable active drainage, ensuring any potential collateral flow would be redirected to the extracorporeal circuit before reaching the brain when transitioning to full TA-NRP. This modified approach was validated in a preclinical model, showing preserved cardiac function after 75 minutes of isolated perfusion. It was then successfully applied in three clinical cases, all resulting in satisfactory transplant outcomes. Bispectral index (BIS) monitoring remained at 0 throughout two procedures, though it should be noted that BIS could only serve as an indirect warning for inadequate cerebral drainage and not as definitive evidence of absent cerebral perfusion. Finally, we evaluated the impact of TA-NRP on DCD lungs. Preclinically, pulmonary function remained satisfactory, with acceptable radiographic and histological findings in both the original and modified TA-NRP models. Clinically, two lung transplants following TA-NRP demonstrated feasibility and acceptable outcomes, highlighting the potential to assess lung grafts in situ. By combining rigorous preclinical experimentation with carefully implemented clinical protocols, this thesis establishes TA-NRP as a feasible and promising approach to expand the DCD donor pool for heart transplantation, while maintaining lung graft quality. Future work should aim to standardize practices across centers, optimize the TA-NRP technique, elucidate the efficacy of strategies to eliminate any potential cerebral circulation, and confirm long-term transplant outcomes of all organs involved
Source: Lirias (KU Leuven)
Author: Vandendriessche, Katrien
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7113335371
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