Fabian Nocke (Essen / DE), Miriam Cantore (Essen / DE), Marina Penzel (Essen / DE), Jasmin Hanke (Hannover / DE), Jörg Optenhöfel (Hannover / DE), Bastian Schmack (Hannover / DE), Arjang Ruhparwar (Hannover / DE), Katja Bettina Ferenz (Essen / DE)
Organ damage due to hypoxia is a well-known problem, not only in emergency medicine, but also during surgical procedures when blood flow is interrupted. Due to their physical properties, previous formulations of our perfluorocarbon-based artificial oxygen carriers (LENOX) were not able to release O2 over a prolonged period of time without recharging at the lung. This work presents a break-through refinement of LENOX that now allows for sustained oxygen supply despite interrupted blood flow.
Physicochemical properties and biocompatibility of the new extended-release oxygen carrier (E-ROC) in the cardioplegic solution Custodiol were tested. A basic characterization of LENOX in Custodiol was carried out with regard to particle size, oxygen release and viscosity. To determine their sustained oxygen release, time-dependent oxygen release measurements of preoxygenated E-ROC were carried out with the PreSens system in hypoxic media inside a hypoxia work station without any cells and in the presence of hypoxic (1 % O2) cardiomyocites (HL-1 cells). HL-1 cells were oxygenated with preoxygenated E-ROC in Custodiol and compared to pure Custodiol without any oxygen carriers and LENOX in Custodiol over a period of 4 h. HIF-1 α via Western blot, ROS production, cell viability, lactate and troponin release were determined as markers for cell status.
The physical release of oxygen from E-ROC was more than twice as long as compared to LENOX loaded with the same amount of oxygen. In contrast to pure Custodiol, only E-ROC oxygenated hypoxic cells adequately and was able to supply the cells with sufficient oxygen for at least 4 h. When analyzing the ROS production, no increase compared to pure Custodiol control was determined. Importantly, the cell viability was not affected by the presence of E-ROC.
With E-ROC we now can provide carrier fluid that provides sustained oxygen supply after singular charging, whereby the amount of oxygen released is sufficient to fuel cellular metabolism and the presence of the product had no negative effect on cells. This opens up a complete new field of application for artificial oxygen carriers in, for example, organ preservation without active perfusion or support during surgical procedures.
The lecithin modified nanoscale oxygen carrier (LENOX) is registered as an invention at European patent office with the application number EP 22193221.3, filed on Aug. 31st, 2022.