Non-invasive measurement of respiratory chain dysfunction following hypothermic renal storage and transplantation.
Ischemia/reperfusion (IR) damage is a major cause of dysfunction in transplanted organs. The objective of the present study was to correlate in vivo measurements of respiratory chain (RC) function with histological and physiological parameters. Non-invasive in situ (surface fluorescence) measurements of mitochondrial NADH and near infrared spectroscopic measurements of cyt aa3 were made in unstored (Group 1) and 72 hour stored (1 to 2 degrees C) (Group 2) autografted rabbit kidneys. The effect of sodium pentobarbitone on NADH levels was investigated. In Group 1, there was a significant change in the redox state of cyt aa3 in all (N = 6) kidneys on reperfusion which correlated with organ viability and increased NADH oxidation and minimal edema on histological examination. In Group 2 there was no significant change in cyt aa3 compared to baseline, and this correlated with poor long term organ viability, slower NADH oxidation, and severe cortical edema. Pentobarbitone inhibition of the RC resulted in rapid and complete reduction of NAD+ in Group 1, but none or only a slight reduction in Group 2. The results demonstrate that it might be possible in future to predict organ viability and histological changes by non-invasive measurements of RC dysfunction in the clinical transplant situation.
Thorniley
M S
MS
Section of Surgical Research, MRC Clinical Research Centre, Middlesex, England, United Kingdom.
Lane
N J
NJ
Manek
S
S
Green
C J
CJ
D000818:Animals; D002470:Cell Survival; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000032:analysis*; D007668:Kidney / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008928:Mitochondria / Q000201:enzymology; D009243:NAD / Q000032:analysis*; D009926:Organ Preservation / Q000009:adverse effects*; D010424:Pentobarbital / Q000494:pharmacology; D011817:Rabbits; D051437:Renal Insufficiency / Q000201:enzymology; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology
D009243:NAD; D003576:Electron Transport Complex IV; D010424:Pentobarbital