title: Dose-ranging study of the performance of the natural oxygen transporter HEMO2 Life in organ preservation.
abstract: 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 HEMO2 Life 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 HEMO2 Life 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 HEMO2 Life 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 HEMO2 Life 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 HEMO2 Life-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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1082, Faculté de Médecine et Pharmacie, Université de Poitiers, Morlaix, France; Hemarina SA, Morlaix, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Mallet
authors.forename: Delphine
authors.initials: D
authors.lastname: Dutheil
authors.forename: Valérie
authors.initials: V
authors.lastname: Polard
authors.forename: Morgane
authors.initials: M
authors.lastname: Rousselot
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Leize
authors.forename: Thierry
authors.initials: T
authors.lastname: Hauet
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Goujon
authors.forename: Franck
authors.initials: F
authors.lastname: Zal
mesh_terms: D000818:Animals; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation / Q000379:methods*; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000737:chemistry*; D010100:Oxygen / Q000378:metabolism*
chemical_list: D019188:Organ Preservation Solutions; D010100:Oxygen
keywords: Dose ranging; HEMO2Life; Ischemia-reperfusion injury; Kidney preservation; Oxygen transporter