DISCONTINUOUS TOTAL PARENTERAL-NUTRITION PREVENTS POSTISCHEMIC MITOCHONDRIAL DYSFUNCTION IN RAT-LIVER

Although discontinuous total parenteral nutrition (d-TPN) has recently been favored for clinical use over continuous total parenteral nutrit ion (c-TPN) to ameliorate liver dysfunction, mechanisms for the protec tion against postoperative liver dysfunction remain unknown. This stud y aimed to examine differences in mitochondrial function in d-TPN-and c-TPN-pretreated livers during ischemia-reperfusion. Rat livers pretre ated with d-TPN or c-TPN were perfused with Krebs-Ringer buffer and we re exposed to 25% low-flow hypoxia followed by reperfusion, Intrahepat ic mitochondrial membrane potential (Delta Psi) and cell viability wer e assessed by dual-color digital microfluorography using rhodamine 123 (Rh123) and propidium iodide (PI), respectively. In response to hypox ia, livers pretreated with c-TPN, d-TPN, and an ordinary chow diet exh ibited a significant Delta Psi reduction among the entire lobules, Upo n reperfusion, the regional Delta Psi values further decreased in the c-TPN liver, whereas those in the d-TPN-treated or chow-treated livers displayed a rapid recovery toward the control levels. The severity of cell injury did not differ among the groups, showing that the reperfu sion-induced Delta Psi drop in the c-TPN-pretreated liver is not a con sequence of cell injury. Differences in the Delta Psi drop among the g roups appear to occur irrespective of those in the glycogen storage, b ecause the livers undergoing d-TPN display a marked Delta Psi recovery even when reperfused at the end of a fasted state. These results indi cate that c-TPN, but not d-TPN, jeopardizes mitochondrial re-energizat ion and suggest that a circadian pattern of the TPN serves as a potent ially beneficial strategy to reduce the risk of postischemic mitochond rial dysfunction in the liver.