MONITORING OF SURFACE MITOCHONDRIAL NADH LEVELS AS AN INDICATION OF ISCHEMIA DURING LIVER ISOGRAFT TRANSPLANTATION

Ischemia-reperfusion injury is a major cause of transplant dysfunction . One feature of this damage is mitochondrial dysfunction. The objecti ve of this study was to determine whether surface fluorometric measure ments of mitochondrial NADH can be made, and if the technique can dete ct differences in mitochondrial respiration between minimally stored 1 to 2 degrees C for 25 minutes (group 1, control) transplanted livers and those stored in hypertonic citrate at 1 to 2 degrees C (group 2) f or 24 hours before transplantation. Measurements were made in livers i sografted in 20 male Lewis rats. The technique is sufficiently sensiti ve to detect increased (nicotinamideadenine dinucleotide (NADH) during dissection of hepatic vessels before ligation 0.52 +/- 0.04 (n = 14, P < .03) compared with the in situ exposed Liver, 0.43 +/- 0.02 n = 14 ). Complete hepatic ligation resulted in a significant increase in NAD H (1.22 +/- 0.10, n = 14), P < .0001) compared with hepatic artery lig ation, which did not increase NADH levels. After storage, NADH levels increased (P < .02) but there was no significant difference between gr oups. In group 1, completion of portal vein (PV), suprahepatic vena ca va (SVC), and descending vena cava anastomoses resulted in decreased N ADH levels toward those after preparation of the vessels before ligati on. However, there was a significant difference (P < .004) between the 25-minute and the 24-hour stored livers, 0.56 +/- 0.07 versus 0.23 +/ - 0.04, respectively. On final revascularisation, NADH returned to pre ligation values in group 1 but there was a highly significant differen ce between groups 1 (0.42 +/- 0.03) and 2 (0.22 +/- 0.02) (P < .0003) equivalent to 89% and 100% oxidation, This abnormal maximal level of N ADH oxidation (100%) in the 24-hour stored livers is suggestive of mit ochondrial dysfunction, These results show that it might be possible t o predict organ viability by noninvasive measurements of respiratory c hain dysfunction in the clinical transplant situation.