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Updated: Nov 19, 2025
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
Comparison of Experimental Rat Models in Donation After Circulatory Death (DCD): in-situ vs. ex-situ Ischemia
Maria Arnold1, Natalia Méndez-Carmona1, Rahel K Wyss1
1Department of Cardiovascular Surgery, Inselspital, Bern University Hospital and Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
Insights
Donation after circulatory death (DCD) hearts show reduced recovery due to pre-procurement ischemia. Cardioplegic storage partially improves function in this DCD rat model.
Area of Science:
- Cardiology
- Transplantation Science
- Physiology
Background:
- Donation after circulatory death (DCD) can increase donor heart availability.
- Warm ischemia during DCD poses risks to cardiac graft quality.
- Understanding physiological changes during DCD is crucial for improving outcomes.
Purpose of the Study:
- To characterize physiological changes in a rat model of DCD with in-situ ischemia.
- To evaluate the impact of cardioplegic graft storage on DCD hearts.
- To compare post-ischemic cardiac recovery with an ex-situ ischemia model.
Main Methods:
- Simulated DCD in Wistar rats via diaphragm transection.
- Hearts underwent either no ischemia or 27 minutes of in-situ ischemia.
- Ex-situ hearts received cardioplegic flush and cold storage before reperfusion.
Main Results:
- In-situ ischemia led to donor heart hypoxia, hemodynamic changes, and elevated catecholamines/fatty acids.
- Post-ischemic contractile recovery was significantly lower in the in-situ model versus the ex-situ model.
- Cardioplegic storage improved developed pressure-heart rate product but not cardiac output.
Conclusions:
- The in-situ DCD model reveals systemic changes affecting heart recovery.
- Hearts from the in-situ model showed poorer functional recovery compared to the ex-situ model.
- Cardioplegic storage partially mitigates functional deficits in DCD hearts.
Abstract:
Introduction: 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 in-situ 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 ex-situ ischemia model. Methods: Following general anesthesia in male, Wistar rats (404 ± 24 g, n = 25), withdrawal of life-sustaining therapy was simulated by diaphragm transection. Hearts underwent no ischemia or 27 min in-situ ischemia and were explanted. Ex situ, 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 ex-situ ischemia model (n = 18). Results: 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 in-situ ischemia model compared to the ex-situ model, and the addition of cardioplegic storage improved developed pressure-heart rate product, but not cardiac output. Conclusion: The in-situ model provides insight into conditions to which the heart is exposed before procurement. Compared to an entirely ex-situ ischemia model, hearts of the in-situ model demonstrated a lower post-ischemic functional recovery, potentially due to systemic changes prior to ischemia, which are partially abrogated by cardioplegic graft storage.
