Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO₂life^®in pig lung transplantation model

Abstract

We describe the results of adding a new biological agent HEMOlife to a standard preservation solution for hypothermic static lung preservation aiming to improve early functional parameters after lung transplantation. HEMOlife is a natural oxygen carrier extracted from Arenicola marina with high oxygen affinity developed as an additive to standard organ preservation solutions. Standard preservation solution (Perfadex) was compared with Perfadex associated with HEMOlife and with sham animals after 24 h of hypothermic preservation followed by lung transplantation. During five hours of lung reperfusion, functional parameters and biomarkers expression in serum and in bronchoalveolar lavage fluid (BALF) were measured. After five hours of reperfusion, HEMOlife group led to significant improvement in functional parameters: reduction of graft vascular resistance (p < .05) and increase in graft oxygenation ratio (p < .05). Several ischemia-reperfusion related biomarkers showed positive trends in the HEMOlife group: expression of HMG B1 in serum tended to be lower in comparison (2.1 ± 0.8 vs. 4.6 ± 1.5) with Perfadex group, TNF-α and IL-8 in BALF were significantly higher in the two experimental groups compared to control (p < .05). During cold ischemia, expression of HIF1α and histology remained unchanged and similar to control. Supplementation of the Perfadex solution by an innovative oxygen carrier HEMOlife during hypothermic static preservation improves early graft function after prolonged cold ischemia in lung transplantation.

First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study

“…In a model of isolated perfused heart in rats, M101 significantly improved the postischemic recovery of heart function and provided a higher coronary flow . In a pig lung allotransplantation model, M101 led to significant improvement in functional parameters: graft vascular resistance and graft oxygenation ratio …”

“…The addition of M101 to preservation solution prevents the progressive decline of the dissolved oxygen concentration . The efficacy of M101 used ex vivo as an additive to preservation solutions for preventing ischemia/reperfusion injuries has been demonstrated in preclinical studies in kidney, heart, and lung . We designed the OXYgen carrier for Organ Preservation (OXYOP) study to analyze the safety and performance of the oxygen carrier M101 in renal transplantation.…”

Artificial Oxygen Carriers—Past, Present, and Future—a Review of the Most Innovative and Clinically Relevant Concepts

“…A clinical phase I open label trial in kidney transplantation [cold storage in Belzer (University of Wisconsin) versus hypothermic machine perfusion with Belzer (University of Wisconsin) 1 Hemo2life before transplantation] was completed in February 2018 (NCT02652520). Furthermore, Hemo2life improved static storage of donor hearts prior to transplantation in a preclinical animal model (Teh et al, 2017) and early graft function after hypothermic static preservation after prolonged cold ischemia of a pig lung (Glorion et al, 2018).…”

Beneficial effects of the novel marine oxygen carrier M101 during cold preservation of rat and human pancreas

“…M101 is derived from a marine poikilotherm invertebrate that is not able to control its body temperature and undergoes marked seasonal and external daily temperature fluctuations. Efficacy and safety of M101 in organ preservation has been shown to improve graft function for clinical studies on kidney and face transplantation, and for pre‐clinical studies on the kidney, lung and heart . Additionally, its ease of use (the molecule can simply be added to the preservation solution) makes it of interest for cold organ preservation, either under static storage or with machine perfusion …”

“…Efficacy and safety of M101 in organ preservation has been shown to improve graft function for clinical studies on kidney and face transplantation, and for pre-clinical studies on the kidney, lung and heart. [21][22][23] Additionally, its ease of use (the molecule can simply be added to the preservation solution) makes it of interest for cold organ preservation, either under static storage or with machine perfusion. 24,25 The goal of the present study was to identify the impact of cold ischaemia on pancreatic islets through examination of the efficacy of M101 on pancreas cold preservation, using both rat and human models.…”