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Artificial oxygen carriers in organ preservation: Dose dependency in a rat model of ex‐vivo normothermic kidney perfusion
Author(s) -
Jägers Johannes,
Kirsch Michael,
Cantore Miriam,
Karaman Ozan,
Ferenz Katja Bettina
Publication year - 2022
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/aor.14264
Subject(s) - ex vivo , perfusion , in vivo , kidney , medicine , oxygen , biomedical engineering , chemistry , cardiology , biology , microbiology and biotechnology , organic chemistry
Organ preservation through ex‐vivo normothermic perfusion (EVNP) with albumin‐derived perfluorocarbon‐based artificial oxygen carriers (A‐AOCs) consisting of albumin‐derived perfluorodecalin‐filled nanocapsules prior to transplantation would be a promising approach to avoid hypoxic tissue injury during organ storage. Methods The kidneys of 16 rats underwent EVNP for 2 h with plasma‐like solution (5% bovine serum albumin, Ringer‐Saline, inulin) with or without A‐AOCs in different volume fractions (0%, 2%, 4%, or 8%). Cell death was determined using TdT‐mediated dUTP‐biotin nick end labeling (TUNEL). Aspartate transaminase (AST) activity in both perfusate and urine as well as the glomerular filtration rate (GFR) were determined. The hypoxia inducible factors 1α and 2α (HIF‐1α und ‐2α) were quantified in tissue homogenates. Results GFR was substantially decreased in the presence of 0%, 2%, and 8% A‐AOC but not of 4%. In accordance, hypoxia‐mediated cell death, as indicated by both AST activity and TUNEL‐positive cells, was significantly decreased in the 4% group compared to the control group. The stabilization of HIF‐1α and 2α decreased with 4% and 8% but not with 2% A‐AOCs. Conclusion The dosage of 4% A‐AOCs in EVNP was most effective in maintaining the physiological renal function.