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Volume 23
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Article

Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation

by
Gábor Szabó
1,2,
Sivakkanan Loganathan
1,2,*,
Sevil Korkmaz-Icöz
1,2,
Ágnes Balogh
3,4,
Zoltan Papp
3,4,
Paige Brlecic
1,2,
Péter Hegedüs
2,
Tamás Radovits
1,5,
Matthias Karck
1,
Béla Merkely
2 and
Gábor Veres
1,2
1
Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany
2
Department of Cardiac Surgery, University of Halle (Saale), 06120 Halle, Germany
3
Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
4
HAS-US Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Science, 1122 Budapest, Hungary
5
Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(13), 7453; https://doi.org/10.3390/ijms23137453
Submission received: 29 May 2022 / Revised: 23 June 2022 / Accepted: 30 June 2022 / Published: 5 July 2022
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Demand for organs is increasing while the number of donors remains constant. Nevertheless, not all organs are utilized due to the limited time window for heart transplantation (HTX). Therefore, we aimed to evaluate whether an iron-chelator-supplemented Bretschneider solution could protect the graft in a clinically relevant canine model of HTX with prolonged ischemic storage. HTX was performed in foxhounds. The ischemic time was standardized to 4 h, 8 h, 12 h or 16 h, depending on the experimental group. Left ventricular (LV) and vascular function were measured. Additionally, the myocardial high energy phosphate and iron content and the in-vitro myocyte force were evaluated. Iron chelator supplementation proved superior at a routine preservation time of 4 h, as well as for prolonged times of 8 h and longer. The supplementation groups recovered quickly compared to their controls. The LV function was preserved and coronary blood flow increased. This was also confirmed by in vitro myocyte force and vasorelaxation experiments. Additionally, the biochemical results showed significantly higher adenosine triphosphate content in the supplementation groups. The iron chelator LK614 played an important role in this mechanism by reducing the chelatable iron content. This study shows that an iron-chelator-supplemented Bretschneider solution effectively prevents myocardial/endothelial damage during short- as well as long-term conservation.
Keywords: custodiol; orthotopic heart transplantation; iron chelator custodiol; orthotopic heart transplantation; iron chelator

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MDPI and ACS Style

Szabó, G.; Loganathan, S.; Korkmaz-Icöz, S.; Balogh, Á.; Papp, Z.; Brlecic, P.; Hegedüs, P.; Radovits, T.; Karck, M.; Merkely, B.; et al. Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation. Int. J. Mol. Sci. 2022, 23, 7453. https://doi.org/10.3390/ijms23137453

AMA Style

Szabó G, Loganathan S, Korkmaz-Icöz S, Balogh Á, Papp Z, Brlecic P, Hegedüs P, Radovits T, Karck M, Merkely B, et al. Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation. International Journal of Molecular Sciences. 2022; 23(13):7453. https://doi.org/10.3390/ijms23137453

Chicago/Turabian Style

Szabó, Gábor, Sivakkanan Loganathan, Sevil Korkmaz-Icöz, Ágnes Balogh, Zoltan Papp, Paige Brlecic, Péter Hegedüs, Tamás Radovits, Matthias Karck, Béla Merkely, and et al. 2022. "Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation" International Journal of Molecular Sciences 23, no. 13: 7453. https://doi.org/10.3390/ijms23137453

APA Style

Szabó, G., Loganathan, S., Korkmaz-Icöz, S., Balogh, Á., Papp, Z., Brlecic, P., Hegedüs, P., Radovits, T., Karck, M., Merkely, B., & Veres, G. (2022). Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation. International Journal of Molecular Sciences, 23(13), 7453. https://doi.org/10.3390/ijms23137453

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