IMPAIRMENT OF HEPATIC MITOCHONDRIAL RESPIRATORY-FUNCTION FOLLOWING STORAGE AND ORTHOTOPIC TRANSPLANTATION OF RAT LIVERS

Prolonged storage of organs for transplant results in tissue damage wh ich may be compounded on reperfusion of the graft tissue. The effect o f storage limes was examined on hepatic mitochondrial oxygen consumpti on and activities of complexes I, II-III, TV, and V in mitochondria is olated from rat liver isografts stored for 25 min and 24 h pre-and pos ttransplantation. 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 part ially recovered to control levels following 3 h of reperfusion after t ransplantation. 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 respira tion. PAD-linked respiration parameters were significantly (P < 0.05) affected in livers subjected to prolonged (24 h) storage or transplant ation. These data suggest that a loss of membrane integrity coupled wi th an inhibition of Complexes I and V and an involvement of Complex II -III in 24-h stored hepatic transplants accounts for mitochondrial res piratory dysfunction in hepatic transplantation injury. No indication of Complex IV damage was found in this study. This study shows that da mage to specific mitochondrial complexes occurs as a consequence of hy pothermic ischemic injury. (C) 1998 Academic Press.