Attenuated Cold Storage Injury of Rat Livers Using a Modified HTK Solution

• Published in: The Journal of surgical research 2008-05, Vol.146 (1), p.49-56
• Main Authors: Bahde, Ralf, M.D, Palmes, Daniel, M.D, Gemsa, Oliver, M.D, Minin, Evgeni, M.D, Stratmann, Udo, M.D, de Groot, Herbert, M.D, Rauen, Ursula, M.D, Spiegel, Hans-Ullrich, M.D
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Bile - metabolism; Biological and medical sciences; Blood Pressure - physiology; Cryopreservation - methods; Disease Models, Animal; General aspects; Glucose - pharmacology; Heart Rate - physiology; histidine-tryptophane-ketoglutarate solution (HTK); L-Lactate Dehydrogenase; Liver - blood supply; Liver - drug effects; Liver - pathology; liver transplantation; Liver Transplantation - methods; Liver, biliary tract, pancreas, portal circulation, spleen; Male; Mannitol - pharmacology; Medical sciences; Microcirculation - physiology; organ preservation; Organ Preservation Solutions - pharmacology; Potassium Chloride - pharmacology; Procaine - pharmacology; Rats; Rats, Inbred Lew; Reperfusion Injury - enzymology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Time Factors
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2007.08.011

Background Preservation injury is a main factor leading to graft failure in liver transplantation. The aim of the study was to minimize preservation injury by modifications of the histidine-tryptophan-ketoglutarate (HTK) solution (incorporation of N -acetyl-histidine, aspartate, glycine, alanine, and arginine). Materials and methods The study was carried out in rats and subdivided into four parts. (1) Systemic toxicity of the modified HTK solution in comparison to the standard HTK solution was tested. (2) Hemodynamic and microcirculatory parameters were analyzed after i.v. injection of the respective solution. (3) Preservation injury after cold storage for different periods of time was assessed microscopically. (4) Reperfusion injury was analyzed in the isolated perfused liver by enzyme release and bile production. Results Blood values, hemodynamic and microcirculatory parameters after i.v. and i.p. application did not significantly differ from control. The modified HTK solution led to an attenuated preservation injury after cold preservation for 24 h compared with standard HTK solution. There was a significantly decreased lactate dehydrogenase release after ischemia for 72 h and reperfusion using the modified solution. After 24 h cold storage and reperfusion the apoptosis index was reduced and bile production significantly increased. Conclusion Optimizing the HTK solution may be a promising therapeutic strategy for attenuation of cold storage injury.