Fabian Nocke (Essen/ DE), Dr. Miriam Cantore (Essen/ DE), Marina Elisabeth Penzel (Essen/ DE), Prof. Dr. Andrea Ulrike Steinbicker (Frankfurt a. M./ DE), Prof. Dr. Katja Bettina Ferenz (Essen/ DE)
Background
Normothermic machine perfusion relies on sufficient O2 supply, while availability of blood by the donor is limited. Artificial oxygen carriers (AOC) based on perfluorocarbons (PFC) can replace blood, as they are synthetic, fully halogenated alkanes, physically dissolving respiratory gases & are of unlimited availability. PFCs must be emulsified for use in aqueous media, which rises stability issues.[1]
Methods
A new type of PFC-based AOC was developed by using an emulsifier combination of albumin & lecithin. A special high pressure homogenizer (Microfluidizer™) with ice cooling was used to synthesize the novel lecithin-modified nanoscale oxygen carriers with a perfluorodecalin core (LENOX).[2] LENOX were synthesized in water, Custodiol™ and STEEN Solution™. The applicability of LENOX for machine perfusion was tested by circulating LENOX in an ex situ perfusion circuit without organ at 37 °C for 4 h. Samples were taken at regular intervals and analyzed by e.g. dynamic light scattering (size), rheometry (viscosity) & a blood gas analyzer (pH, O2 release, free ions). Error bars shown in the figures represent standard deviation of n=3 experiments.
Results
LENOX could be synthesized in all three media and formed a sufficiently stable emulsion. The particle size analysis showed a similar behavior for LENOX in water & Custodiol™. LENOX in STEEN Solution™ revealed significantly larger mean particle diameter than the other media. However, LENOX in all 3 media were stable over 240 min & small enough for use in machine perfusion settings (Fig. 1).
All three variants of LENOX showed the same amount of O2 release, which, due to non-existent consumption, reached a maximum of about 320 hPa (240 mmHg) after 60 min. The different perfusion media depicted no influence on the functionality of LENOX (Fig. 2).
Conclusion
The novel AOC LENOX revealed high stability despite the difficult requirements of organ perfusion. Compatibility with clinically relevant perfusion media such as Custodiol™ or STEEN Solution™ makes LENOX an interesting alternative to blood for organ perfusion.
Offenlegung Interessenkonflikt:
Three of the named authors are listed as inventors in the given patent