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 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 degrees C for 25 minutes (group 1, control) transplanted livers and those stored in hypertonic citrate at 1 to 2 degrees 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 (nicotinamide-adenine 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Thorniley
M S
MS
Department of Surgical Research, Northwick Park Institute for Medical Research, Northwick Park Hospital, Harrow, Middlesex, UK.
Simpkin
S
S
Fuller
B
B
Jenabzadeh
M Z
MZ
Green
C J
CJ
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D007511:Ischemia / Q000175:diagnosis*; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation; D016031:Liver Transplantation / Q000379:methods / Q000502:physiology*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D008991:Monitoring, Physiologic / Q000379:methods; D009243:NAD / Q000032:analysis* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011917:Rats, Inbred Lew; D013050:Spectrometry, Fluorescence; D014185:Transplantation, Isogeneic
D015415:Biomarkers; D009243:NAD