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Updated: Aug 19, 2026
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
Coronary endothelial dysfunction of isolated hearts subjected to prolonged cold storage: patterns and contributing
E Kevelaitis1, N C Nyborg, P Menasché
1Department of Physiology, Medical University, Kaunas, Lithuania. ekeve@kma.lt
Insights
Prolonged cold heart storage impairs coronary artery function, especially in distal vessels. Storage duration and solution type significantly affect endothelial and smooth muscle function, impacting transplant outcomes.
Area of Science:
- Cardiovascular Research
- Transplantation Medicine
- Vascular Biology
Background:
- Endothelial dysfunction is crucial in heart transplant complications like low coronary flow and cardiac allograft vasculopathy.
- Optimal preservation of coronary endothelium during cold storage is vital for successful heart transplantation.
Purpose of the Study:
- To investigate the impact of extended cold storage on endothelial and smooth muscle function.
- To compare the effects on proximal (epicardial) and distal (intramyocardial) coronary arteries.
Main Methods:
- Isolated rat hearts were cold-stored using Celsior or Plegisol solutions for varying durations (10, 15, 30 hours).
- Coronary artery segments were analyzed using an isometric wire myograph for functional studies.
- Control groups included fresh vessels and vessels stored in vitro.
Main Results:
- Endothelium-dependent relaxation to acetylcholine was reduced in distal arteries after 10 hours and in both proximal and distal arteries with longer storage or specific solutions.
- Endothelial function impairment was more severe with Plegisol/saline compared to Celsior after 15 hours.
- Basal myogenic tone increased, and sensitivity to vasoconstrictors like 5-hydroxytryptamine was elevated, particularly in distal arteries and with prolonged storage.
Conclusions:
- Extended cold ischemic heart storage leads to coronary endothelial dysfunction.
- This dysfunction is more pronounced in distal coronary arteries compared to proximal ones.
- The duration of storage and the composition of the preservation solution are key factors influencing vascular function post-transplant.
Background:
A key role of endothelial dysfunction in the pathogenesis of early low coronary flow of heart transplants and late cardiac allograft vasculopathy indicates the importance of optimal coronary endothelial preservation during cold heart storage. We designed this study to investigate the effect of prolonged cold storage on endothelial and smooth muscle function of proximal (epicardial) and distal (intramyocardial) coronary arteries.
Methods:
Four groups of isolated rat hearts were subjected to cold cardioplegic perfusion and immersed in storage medium at 4 degrees C. In groups 1, 2, and 3, hearts were perfused with and stored in Celsior solution for 10, 15, and 30 hours, respectively. In group 4, hearts were perfused with Plegisol and stored in saline for 15 hours. At the end of cold heart storage, arterial segments were taken from the proximal and distal parts of the left coronary artery and mounted on an isometric wire myograph for functional studies. In fifth group, proximal and distal segments of coronary artery isolated from fresh hearts were used as controls. At the end of control measurements, these vessels were used for storage in vitro at 4 degrees C for 15 hours in saline (group 5A) or Celsior (group 5B).
Results:
The endothelium-dependent relaxation to acetylcholine was reduced in distal coronary arteries in group 1, and in both proximal and distal coronary artery segments in groups 2, 3, 4, and 5A. Endothelial function was significantly more impaired in both proximal and distal coronary arteries in group 4, as compared with group 2. The impairment of relaxation to acetylcholine was more pronounced following cold storage of the heart than after a similarly long storage of the isolated vessels. The endothelium-independent relaxations to isoprenaline did not differ among all groups. The basal myogenic tone was increased in distal coronary arteries in group 1, and in both proximal and distal coronary arteries in groups 2, 3, 4, and 5A. The sensitivity to the vasoconstricting action of 5-hydroxytryptamine was increased in distal coronary arteries in group 2, and in both proximal and distal coronary arteries in groups 3, 4, and 5A.
Conclusions:
Prolonged ischemic cold heart storage induces coronary endothelial dysfunction that is more pronounced in distal than in proximal arteries and is related to the duration of heart storage and the composition of storage medium.
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