Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA233

Poster Communications

Does glucose-dependent cross-linking influence in vivo toxicity and compatibility of albumin-derived perfluorocarbon-based artificial oxygen carriers?

A. Scheer1, C. Mayer2, J. Linders2, M. Kirsch3, K. Ferenz1

1. Institute of Physiology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany. 2. Institute of Physical Chemistry, University of Duisburg-Essen, Essen, Germany. 3. Institute of Physiological Chemistry, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.

Within the last years several studies with albumin-derived perfluorocarbon-based artificial oxygen carriers (A-AOCs) with different shell materials were carried out successfully (1-3). In order to further prolong the circulation half-time of the capsules a new approach, the synthesis of glucose-crosslinked albumin-derived artificial oxygen carriers (gcA-AOCs), was tested for its in vivo compatibility. To demonstrate safety of our artificial oxygen carriers in a top load model (TL), we applied such solutions (+ 1/6 of blood volume) in the presence or in the absence of gcA-AOCs (control), respectively. 16 healthy male Wistar Rats were anesthetized with isoflurane (2.0 % in 100 % medical O2 at 4.0 l/min for induction, 1.5-2.0 % isoflurane in 100 % medical O2 at 1.0 l/min throughout the experiment) through face masks connected to a vaporizer. For analgesia, they received ketamine (50 mg/kg body weight) and lidocaine (5 mg/kg body weight) subcutaneously into the right chest wall. Portex catheters were placed within the right femoral artery (biomonitoring) and the right femoral vein (infusion of gcA-AOCs or 0.9 % normal saline (NS), 10 ml/kg body weight). After the infusion period (30 min) rats were further observed up to 180 min. During TL systemic parameters, plasma enzyme activities and acid base status were continuously monitored. To determine the therapeutically relevant oxygen capacities, oxygen content donated by gcA-AOCs was discovered using a respirometer. Oxygen resolved in buffer was removed by adding yeast that was subsequently inactivated by adding potassium cyanide to prevent aerobic metabolism of the yeast in the processing experiment. After oxygen loading, gcA-AOCs or 0.9 % NS were applied to the oxygen-free measuring chambers of the respirometer under exclusion of air. Results of 8 vol. % gcA-AOCs were compared to 8 vol. % A-AOCs in 0.9 % NS/ 5 % human serum albumin (5 % HSA)(4). During infusion systemic parameters (e.g. blood pressure, pH, pO2 and pCO2) were unaffected in all groups (gcA-AOCs, A-AOCs and controls). Compared to all other groups, gcA-AOCs displayed increased plasma enzyme activities. Likewise gcA-AOCs released considerably more oxygen compared to A-AOCs. The present study demonstrates that toxicity of equal doses of A-AOCs depends on the structure of the shell material. Using the same molecule (albumin) to construct the shell does not guarantee to sustain safety profiles and oxygen release as proven by the glucose-dependent cross-linking of A-AOCs. Because of the high oxygen release we are currently looking for more detailed information on the physico-chemical properties of gcA-AOCs.

Where applicable, experiments conform with Society ethical requirements