AUTHOR=Arnold Maria , Méndez-Carmona Natalia , Wyss Rahel K. , Joachimbauer Anna , Casoni Daniela , Carrel Thierry , Longnus Sarah 

TITLE=Comparison of Experimental Rat Models in Donation After Circulatory Death (DCD): in-situ vs. ex-situ Ischemia

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=7

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2020.596883

DOI=10.3389/fcvm.2020.596883

ISSN=2297-055X

ABSTRACT=<p><bold>Introduction:</bold> Donation after circulatory death (DCD) could substantially improve donor heart availability. However, warm ischemia prior to procurement is of particular concern for cardiac graft quality. We describe a rat model of DCD with <italic>in-situ</italic> ischemia in order to characterize the physiologic changes during the withdrawal period before graft procurement, to determine effects of cardioplegic graft storage, and to evaluate the post-ischemic cardiac recovery in comparison with an established <italic>ex-situ</italic> ischemia model.</p><p><bold>Methods:</bold> Following general anesthesia in male, Wistar rats (404 ± 24 g, <italic>n</italic> = 25), withdrawal of life-sustaining therapy was simulated by diaphragm transection. Hearts underwent no ischemia or 27 min <italic>in-situ</italic> ischemia and were explanted. <italic>Ex situ</italic>, hearts were subjected to a cardioplegic flush and 15 min cold storage or not, and 60 min reperfusion. Cardiac recovery was determined and compared to published results of an entirely <italic>ex-situ</italic> ischemia model (<italic>n</italic> = 18).</p><p><bold>Results:</bold> In donors, hearts were subjected to hypoxia and hemodynamic changes, as well as increased levels of circulating catecholamines and free fatty acids prior to circulatory arrest. Post-ischemic contractile recovery was significantly lower in the <italic>in-situ</italic> ischemia model compared to the <italic>ex-situ</italic> model, and the addition of cardioplegic storage improved developed pressure-heart rate product, but not cardiac output.</p><p><bold>Conclusion:</bold> The <italic>in-situ</italic> model provides insight into conditions to which the heart is exposed before procurement. Compared to an entirely <italic>ex-situ</italic> ischemia model, hearts of the <italic>in-situ</italic> model demonstrated a lower post-ischemic functional recovery, potentially due to systemic changes prior to ischemia, which are partially abrogated by cardioplegic graft storage.</p>