Improvement of Normothermic Ex Vivo Heart Perfusion to Expand the Number and Quality of DCD Donor Organs by Using Artificial Oxygen Carriers

Background: The number of patients waiting for organ transplants significantly exceeds the number of available organ donations. Donations after circulatory death (DCD) are increasingly being considered to address this imbalance, particularly when combined with novel preservation methods. Ex-vivo normothermic machine perfusion (EVNP) meets the metabolic demands of organs, allowing for the assessment of donor organ quality and treatment of marginally perfused organs. In this study, we aim to investigate the potential of perfluorocarbon-based artificial oxygen carriers (A-AOCs) to replace erythrocytes as oxygen carrying component during ex-vivo heart machine perfusion in a porcine DCD model.

Methods: EVNP was established as a physiological model for testing the functionality of A-AOCs in an isolated perfused porcine heart subjected to a warm ischemia time of 25 minutes followed by 25 minutes cold ischemia. The model was established using porcine blood as perfusate. Additional groups, including statically cold stored (SCS) hearts and A-AOC-based EVNP, are currently under investigation. Hemodynamic and biochemical investigations of the preservation fluids were conducted after 1 (T1) and 2 (T2) hours, using blood gas analyzer and photometry. Heart weights were measured before and after perfusion to quantify edema formation.

Results: Perfusion with a sanguine preservation solution maintained a contracting heart for at least 2.5 hours. Perfused hearts (n = 4) gained 58% in weight during perfusion (weight gain: blood = 22.3 ± 3.2 g/h). Lactate consumption was determined with decreasing lactate levels (blood = 0.90 ± 0.11-fold change T1-T2) during EVHP. Cellular damage was quantified using time-resolved measurements of released lactate dehydrogenase (blood = 1.22 ± 0.05-fold change T1-T2) and troponin-I (blood = 2.3 ± 0.4-fold change T1-T2) into the perfusate.

Conclusion: A blood-based normothermic ex vivo perfusion of porcine hearts showed elevated levels of LDH and troponin I, indicating tissue damage likely to be caused by edema formation and defibrillation during the stabilization phase. Nonetheless, the erythrocyte-based perfusate was able to perfuse a porcine heart for at least 2.5 hours. Contractility was successfully regained, and myocardial restoration was demonstrated by lactate extraction. After successful establishment of EVNP, we can now investigate the A-AOCs’ potential to reduce ischemia-related injury of DCD organs.

Publication History

Article published online:
11 February 2025