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Why Belzer UW® Cold Storage Solution? The Difference is in the Solution The European ELTR study of over 20,000 liver transplantations shows that Belzer UW® Cold Storage Solution provides a graft survival advantage over HTK of 6-8% at ischemia times of 6-12 hours—rising to 13% at five years for ischemia times of 12 hours or more.1 (The US UNOS study mirrors this data.) 6-12 Hours of Cold Ischemia Time Log rank test, p<0.0001 100 UW HTK 80 80 60 60 Survival (%) Survival (%) 100 12-18 Hours of Cold Ischemia Time 40 Log rank UW vs HTK 20 0 p , <0.0001 1 2 Years 3 40 4 5 0 UW HTK Log rank UW vs HTK 20 UW (n = 10,455); HTK (n = 2,346) 0 Log rank test, p<0.0001 p , <0.0001, UW (n = 1,734); HTK (n = 409) 0 1 2 Years 3 4 5 Adapted from figures 3B and C of the Rene Adam study footnoted above. These components show how Belzer UW® Cold Storage Solution sustains and enhances cellular function in a variety of ways. Component/Trait Benefit HES Prevents edema formation during the flush. Lactobionic Acid & Prevents lethal cell swelling from ischemia and hypothermia. Raffinose Pentahydrate Adenosine Adenine nucleotide precursor accel-erates ATP synthesis at reperfusion to reduce energy depletion. Provides a statistically higher level of ATP. Glutathione Source of glycine, a cytoprotective amino acid. Demonstrates substantial protective effects against reactive 02 species upon ischemia and re-perfusion. Allopurinol Inhibits xanthine oxidase activity and purine metabolism as well as reducing oxygen free radicals. Thermal capacity Cools organs more rapidly. Belzer UW® HTK Yes Yes No No Yes No—Generates minimal ATP Yes No Yes No High Low The patient outcomes are conclusive. The details of these differences explain why Belzer UW® Cold Storage Solution achieves significantly higher graft survival rates than HTK. Different solutions. Different outcomes. THE DIFFERENCE MATTERS. Research Evidence Hydroxyethyl Starch (Pentafraction) Lactobionic Acid (as Lactone) and Raffinose Pentahydrate Adenosine Glutathione Allopurinol Thermal capacity This oncotic agent “plays a key role in preventing tissue edema, and HTK does not contain it when compared to…UW hydroxyethyl starch [HES].” 2 “Various impermeants have been used to sustain the oncotic gradient across the cell membrane and prevent oedema. … UW pioneered the use of lactobionate and raffinose…Lactobionate remains the impermeant choice of having been successfully used in preservation solutions other than UW, being critical to the success of UW, and for its proposed iron chelation properties (cf. oygen-free radicals).” 3 HTK? “…the efficiency of the solution is also strongly dependent on the presence of antioxidants and protective agents. HTK composition is poor in these agents when compared to the other solutions.” 4 In a study of human liver endothelial cells (HLEC), Dr. Hermann Janssen compares Belzer UW with HTK: “Overall, there was a statistically significantly higher content of intracellular ATP in UW-preserved HLEC compared to CS and HTK.” What this means to liver cells is that: “…we concluded from our data that the significantly higher ATP level in UW-preserved HLEC in each interval of ischemia and reperfusion was a major contributing factor to reducing the preservation injury as confirmed by LDH [Lactate dehydrogenase] release and MTT reduction. [MTT=mitochondria to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] This finding gave evidence that, particularly in long-term ischemia, a high intracellular ATP level was beneficial in the preservation of HLEC.” 5 “Both reduced glutathione and allopurinol in UW solution demonstrated substantial protective effects against reactive oxygen species upon ischaemia and re-perfusion.” 6 “…UW contains numerous active agents to replenish energy and scavenge oxygen radicals which are not found in HTK ...” 7 “Heat capacity is significantly higher for UW than for HTK… Prolonged preservation in UW solution results in a better renal function and less tissue damage compared with HTK, possibly due to improved cooling and better cell viability of the graft.” 8 1,2,4 “Compared Efficacy of Preservation Solutions in Liver Transplantation: A Long-Term Graft Outcome Study from the European Liver Transplant Registry”; René Adam et al. American Journal of Transplantation, Februrary 2015 3 “Organ Donation and Transplantion After Cardiac Death”; edited by David Talbot and Anthony M. D’Alessandro, Oxford University Press, 2009 “UW is Superior to Celsior and HTK in the Protection of Human Liver Endothelial Cells Against Preservation Injury”; Hermann Janssen et al.; Liver Transplantation, December 2004 5 Organ Preservation: Current Concepts and New Strategies for the Next Decade; Edgardo E. Guibert, et al. Transfus Med Hemother 2011 Apr; 38(2): 125-142] 6 Hydroxyethyl Starch-Based Preservation Solutions Enhance Gene Therapy Vector Delivery Under Hypothermic Conditions; D. Henry Scot, et. al. Gene Therapy of Liver Disease with Lentiviral Vectors; Pascal van der Wegen, 2009 Erasmus Universiteit Rotterdam 7 “UW is superior compared with HTK after prolonged preservation of renal grafts.”; S. Hoeger, et. al. J Surg Res. 2011 Sep;170(1):e149-57. doi: 10.1016/j.jss.2011.05.020. Epub 2011 Jun 12 8 Belzer UW® Cold Storage Solution (UW Solution) Bridge to Life has an exclusive trademark license from the Wisconsin Alumni Research Foundation (WARF) for the trademark Belzer UW®. Bridge to Life Ltd. | 128 Suber Rd. | Columbia, SC 29210 800-667-9524 | www.bridgetolife.com | [email protected]