Effects of graft preservation conditions on coronary endothelium and cardiac functional recovery in a rat model of donation after circulatory death

Méndez Carmona, Natalia; Wyss, Rahel K.; Arnold, Maria; Segiser, Adrian; Kalbermatter, Nina; Joachimbauer, Anna; Carrel, Thierry P.; Longnus, Sarah L. (2021). Effects of graft preservation conditions on coronary endothelium and cardiac functional recovery in a rat model of donation after circulatory death. Journal of heart and lung transplantation, 40(11), pp. 1396-1407. Elsevier 10.1016/j.healun.2021.07.028

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Background: Use of cardiac grafts obtained with donation after circulatory death (DCD) could significantly improve donor heart availability. As DCD hearts undergo potentially deleterious warm ischemia and reperfusion, clinical protocols require optimization to ensure graft quality. Thus, we investigated effects of alternative preservation conditions on endothelial and/or vascular and contractile function in comparison with the current clinical standard.

Methods: Using a rat DCD model, we compared currently used graft preservation conditions, St. Thomas n°2 (St. T) at 4°C, with potentially more suitable conditions for DCD hearts, adenosine-lidocaine preservation solution (A-L) at 4°C or 22°C. Following general anesthesia and diaphragm transection, hearts underwent either 0 or 18 min of in-situ warm ischemia, were explanted, flushed and stored for 15 min with either St. T at 4°C or A-L at 4°C or 22°C, and then reperfused under normothermic, aerobic conditions. Endothelial integrity and contractile function were determined.

Results: Compared to 4°C preservation, 22°C A-L significantly increased endothelial nitric oxide synthase (eNOS) dimerization and reduced oxidative tissue damage (p < 0.05 for all). Furthermore, A-L at 22°C better preserved the endothelial glycocalyx and coronary flow compared with St. T, tended to reduce tissue calcium overload, and stimulated pro-survival signaling. No significant differences were observed in cardiac function among ischemic groups.

Conclusions: Twenty-two-degree Celsius A-L solution better preserves the coronary endothelium compared to 4°C St. T, which likely results from greater eNOS dimerization, reduced oxidative stress, and activation of the reperfusion injury salvage kinase (RISK) pathway. Improving heart preservation conditions immediately following warm ischemia constitutes a promising approach for the optimization of clinical protocols in DCD heart transplantation.

Keywords: coronary vascular function; donation after circulatory death (DCD); heart transplantation; ischemia-reperfusion; preservation conditions.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Heart Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Herz- und Gefässchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Herz- und Gefässchirurgie

UniBE Contributor:

Méndez Carmona, Natalia, Wyss, Rahel Kathrin, Arnold, Maria Regula, Segiser, Adrian, Kalbermatter, Nina Corinne, Joachimbauer, Anna, Carrel, Thierry, Henning Longnus, Sarah

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1053-2498

Publisher:

Elsevier

Language:

English

Submitter:

Paul Libera

Date Deposited:

22 Sep 2021 14:07

Last Modified:

27 Feb 2024 14:28

Publisher DOI:

10.1016/j.healun.2021.07.028

PubMed ID:

34509349

BORIS DOI:

10.48350/159154

URI:

https://boris.unibe.ch/id/eprint/159154

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