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Dose‐Ranging Study of the Performance of the Natural Oxygen Transporter HEMO 2 L ife in Organ Preservation
Author(s) -
Mallet Vanessa,
Dutheil Delphine,
Polard Valérie,
Rousselot Morgane,
Leize Elisabeth,
Hauet Thierry,
Goujon Jean Michel,
Zal Franck
Publication year - 2014
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.12307
Subject(s) - ranging , oxygen , natural (archaeology) , chemistry , computer science , biology , paleontology , telecommunications , organic chemistry
The intensity of ischemia–reperfusion injury of the donor organ during the preservation phase and after anastomosis is acknowledged as being a key factor for long‐term graft outcome. We previously showed that the addition of 5 g/L of the natural oxygen carrier HEMO 2 L ife was beneficial for the cold static preservation of kidney grafts in both University of Wisconsin ( UW ) and histidine–tryptophan–ketoglutarate solutions. Herein, we refined these findings by evaluating HEMO 2 L ife at various dose levels in UW , both in vitro with endothelial cells and in vivo in a pig kidney autotransplantation preclinical model. We showed in vitro that cells were significantly better preserved with HEMO 2 L ife in a dose‐dependent manner, with benefits in terms of survival, metabolic activity, and cellular integrity. In vivo, serum creatinine measurements at reperfusion confirmed the important benefits of HEMO 2 L ife treatment on function recovery at the dose levels of 1, 2, and 5 g/L . Likewise, histological analysis of kidney parenchyma biopsies from day 7 confirmed the superiority of HEMO 2 L ife‐supplemented UW over UW alone, and there was no difference between the doses. Three months' follow‐up confirmed the trend of the first 2 weeks, with creatinine and fibrosis levels similar to those in pretransplant kidneys.