Monitoring of surface mitochondrial NADH levels as an indication of ischemia during liver isograft transplantation

M. S. Thorniley, S. Simpkin, B. Fuller, M. Z. Jenabzadeh, C. J. Green

Research output: Contribution to journalArticlepeer-review

Abstract

Ischemia-reperfusion injury is a major cause of transplant dysfunction. One feature of this damage is mitochondrial dysfunction. The objective of this study was to determine whether surface fluorometric measurements of mitochondrial NADH can be made, and if the technique can detect differences in mitochondrial respiration between minimally stored 1 to 2°C for 25 minutes (group 1, control) transplanted livers and those stored in hypertonic citrate at 1 to 2°C (group 2) for 24 hours before transplantation. Measurements were made in livers isografted in 20 male Lewis rats. The technique is sufficiently sensitive 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 NADH (1.22 ± 0.10, n = 14), P <.0001) compared with hepatic artery ligation, which did not increase NADH levels. After storage, NADH levels increased (P <.02) but there was no significant difference between groups. In group 1, completion of portal vein (PV), suprahepatic vena cava (SVC), and descending vena cava anastomoses resulted in decreased NADH levels toward those after preparation of the vessels before ligation. 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 preligation values in group 1 but there was a highly significant difference 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 NADH oxidation (100%) in the 24-hour stored livers is suggestive of mitochondrialdysfunction. These results show that it might be possible to predict organ viability by noninvasive measurements of respiratory chain dysfunction in the clinical transplant situation.
Original languageEnglish
Pages (from-to)1602-1609
Number of pages7
JournalHepatology
Volume21
Issue number6
Publication statusPublished - 1995

Keywords

  • Animals
  • analysis: Biological Markers
  • diagnosis: Ischemia
  • blood supply: Liver
  • Liver Circulation
  • methods: Liver Transplantation
  • Male
  • metabolism: Mitochondria, Liver
  • methods: Monitoring, Physiologic
  • analysis: NAD
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Lew
  • Spectrometry, Fluorescence
  • Transplantation, Isogeneic

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