Jacqueline Hausherr (Essen / DE), Miriam Cantore (Essen / DE), Fabian Nocke (Essen / DE), Katja Bettina Ferenz (Essen / DE), Omar Abou-Issa (Essen / DE), Nikolaus Pizanis (Essen / DE), Markus Kamler (Essen / DE)
In heart transplantation, normothermic machine-perfusion (NT-MP) is a new tool to reduce time of ischemia; however warm perfusion requires red blood cells. Perfluorodecalin-based albumin-derived artificial oxygen carriers (A-AOC) have emerged as an universal alternative for erythrocytes.1 An in vivo study has demonstrated the exceptional biocompatibility of A-AOCs when administered intravenously.2 This project aimed to set up a physiological model for heart NT-MP in which A-AOCs can be implemented as blood substitutes.
NT-MP was established as physiological model for testing the functionality of A‑AOCs in an isolated perfused porcine heart. Hemodynamic and biochemical investigations of the preservation fluids were studied by blood gas analyzer and photometry (respons 920).
Preliminary experiments in the established perfusion apparatus showed that the perfusion with a preservation solution was able to maintain a contracting heart for at least three hours. Changes in lactate and glucose levels in the perfusion medium were monitored as metabolic markers. Cellular damage was determined by time-resolved measurements of released lactate dehydrogenase and troponin-I into the perfusate.
Once the experimental setup for perfusing porcine hearts is successfully established, we will explore the potential of A-AOCs to reduce reperfusion-associated acute myocardial infarction (repAMI) during ex vivo heart perfusion. Our group previously demonstrated the successful preservation of isolated rat hearts.3 Hence, decreased repAMI injury is anticipated for NT-MP with A-AOCs.
1 Ferenz, O. Karaman, S. B. Shah in Nanotechnology for Hematology, Blood Transfusion, and Artificial Blood, Elsevier, 2022, pp. 397–427.
2 Wrobeln, J. Laudien, C. Groß-Heitfeld, J. Linders, C. Mayer, B. Wilde, T. Knoll, D. Naglav, M. Kirsch, K. B. Ferenz, European Journal of Pharmaceutics and Biopharmaceutics 2017, 115 , 52-64.
3 Wrobeln, K. D. Schlüter, J. Linders, M. Zähres, C. Mayer, M. Kirsch, K. B. Ferenz, Artificial cells, nanomedicine, and biotechnology 2017, 45, 723.
No conflicts of interest.