Possibility of conditioning predamaged grafts after cold storage: influences of oxygen and nutritive stimulation.
The potential of short-term oxygenated perfusion after cold storage (CS) to reverse deleterious priming of nonheart beating donors grafts should be investigated, addressing the respective role of oxygenation and nutrients or metabolic charge. Livers were retrieved 30 min after cardiac arrest of male Wistar rats and preserved with histidine tryptophan ketoglutarate (HTK)-solution for 18 h by CS. After 16 h, some livers were put on an oxygenated machine-preservation-circuit for the last 2 h and conditioned by cold perfusion with either HTK (conHTK), HTK supplemented with adenosine, phosphate and glucose (conHTK+) or Williams-E solution (conWE). Upon warm reperfusion, postconditioning with any of the solutions led to a significant (three- to fivefold) reduction of parenchymal damage (ALT, GLDH-release) compared with CS. Metabolic recovery (bile production) was also significantly enhanced compared with CS, with best results found after conHTK. The beneficial effect of postconditioning with HTK was associated with a significantly mitigated cleavage of caspase 12 and 3. We conclude from these data that conditioning of predamaged livers is possible even after CS by short-term oxygenated perfusion in the cold and, under these conditions, not depending on energetic support or nutritive stimulation.
Manekeller
Steffen
S
Surgical Research Division, University Clinic of Surgery, Bonn, Germany. chirfor@ukb.uni-bonn.de
Minor
Thomas
T
D000818:Animals; D001483:Base Sequence; D053454:Caspase 12; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003080:Cold Temperature; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000293:injuries / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010100:Oxygen; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051742:Transcription Factor CHOP / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP
D053454:Caspase 12; D053148:Caspase 3; D020169:Caspases; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D019188:Organ Preservation Solutions; D010100:Oxygen; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C506444:CASP12 protein, human; C505407:CASP3 protein, human; C506443:Casp12 protein, rat; C505410:Casp3 protein, rat