title: Controlled therapeutic gas delivery systems for quality-improved transplants.
abstract: Therapeutic gases enriched into perfusion solutions have been effectively used for the improvement of organ transplant quality. At present, the enrichment of perfusion solutions with gases requires complex machinery/containers and handling precautions. Alternatively, the gas is generated within the perfusion solution by supplemented carbonylated transition metal complexes with associated toxicological concerns when these metals contact the transplant. Therefore, we developed therapeutic gas releasing systems (TGRSs) allowing for the controlled generation and release of therapeutic gases (carbon monoxide and hydrogen sulfide) from otherwise hermetically sealed containers, such that the perfusion solution for the transplant is saturated with the gas but no other components from the TGRS are liberated in the solution. The release from the TGRS into the perfusion solution can be tailored as a function of the number and thickness of gas permeable membranes leading to release patterns having been linked to therapeutic success in previous trials. Furthermore, the surrogate biomarker HMGB1 was significantly downregulated in ischemic rat liver transplants perfused with enriched CO solution as compared to control. In conclusion, the TGRS allows for easy, reliable, and controlled generation and release of therapeutic gases while removing safety concerns of current approaches, thereby positively impacting the risk benefit profile of using therapeutic gases for transplant quality improvement in the future.
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Steiger
authors.affiliation: Department of Anaesthesia and Critical Care, University of Wuerzburg, Oberduerrbacherstraße 6, DE-97080 Wurzburg, Germany; Department of Anesthesiology and Intensive Care Medicine, University Medical Center Freiburg, Hugstetter Str. 55, DE-79106 Freiburg, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Wollborn
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Gutmann
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zehe
authors.affiliation: Department of Anaesthesia and Critical Care, University of Wuerzburg, Oberduerrbacherstraße 6, DE-97080 Wurzburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wunder
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, DE-97074 Wuerzburg, Germany. Electronic address: l.meinel@pharmazie.uni-wuerzburg.de.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Meinel
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage*; D015536:Down-Regulation / Q000235:genetics; D065546:Drug Liberation; D024243:HMGB1 Protein / Q000235:genetics; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D016031:Liver Transplantation / Q000379:methods* / Q000592:standards; D008297:Male; D016377:Organ Transplantation / Q000379:methods* / Q000592:standards; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D024243:HMGB1 Protein; D002248:Carbon Monoxide; D006862:Hydrogen Sulfide
keywords: CORM; Diffusion; HMGB1; Therapeutic gas; Transplant