title: Impairment of hepatic mitochondrial respiratory function following storage and orthotopic transplantation of rat livers.
abstract: Prolonged storage of organs for transplant results in tissue damage which may be compounded on reperfusion of the graft tissue. The effect of storage times was examined on hepatic mitochondrial oxygen consumption and activities of complexes I, II-III, IV, and V in mitochondria isolated from rat liver isografts stored for 25 min and 24 h pre- and posttransplantation. While Complex I activity was significantly (P < 0.05) inhibited under all the conditions studied, Complex II-III activity was only significantly (P < 0.05) reduced following transplantation of 24-h stored tissue. Complex IV activity remained unchanged under all the conditions studied. Although Complex V activity was significantly damaged within the first 25 min of ischemia, activity values were partially recovered to control levels following 3 h of reperfusion after transplantation. Prolonged (24 h) storage induced decreases in Complex V activity which were irrecoverable. Mitochondria subjected to 25 min ischemia alone also showed a significant (P < 0.01) decrease in NAD(+)-linked respiratory control indices due to a stimulated state 4 rate. The 24-h storage and transplantation brought about a significantly (P < 0.001) greater inhibition of respiratory control and state 3 respiration. FAD-linked respiration parameters were significantly (P < 0.05) affected in livers subjected to prolonged (24 h) storage or transplantation. These data suggest that a loss of membrane integrity coupled with an inhibition of Complexes I and V and an involvement of Complex II-III in 24-h stored hepatic transplants accounts for mitochondrial respiratory dysfunction in hepatic transplantation injury. No indication of Complex IV damage was found in this study. This study shows that damage to specific mitochondrial complexes occurs as a consequence of hypothermic ischemic injury.
authors.affiliation: Department of Surgical Research, Northwick Park Institute for Medical Research, Northwick Park Hospital, Harrow, United Kingdom.
authors.forename: I A
authors.initials: IA
authors.lastname: Sammut
authors.forename: M S
authors.initials: MS
authors.lastname: Thorniley
authors.forename: S
authors.initials: S
authors.lastname: Simpkin
authors.forename: B J
authors.initials: BJ
authors.lastname: Fuller
authors.forename: T E
authors.initials: TE
authors.lastname: Bates
authors.forename: C J
authors.initials: CJ
authors.lastname: Green
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015925:Cryopreservation; D004579:Electron Transport; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply / Q000293:injuries; D016031:Liver Transplantation / Q000502:physiology; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009926:Organ Preservation / Q000009:adverse effects*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control
chemical_list: D009243:NAD; D005182:Flavin-Adenine Dinucleotide; D000255:Adenosine Triphosphate