Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver.
Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α-2-macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis.
Department of Surgical Gastroenterology L, Aarhus University Hospital, Aarhus, Denmark.
Anders R
AR
Knudsen
Department of Surgical Gastroenterology L, Aarhus University Hospital, Aarhus, Denmark.
Kasper J
KJ
Andersen
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Stephen
S
Hamilton-Dutoit
Stereology & Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark.
Jens R
JR
Nyengaard
Department of Surgical Gastroenterology L, Aarhus University Hospital, Aarhus, Denmark.
Frank V
FV
Mortensen
D000410:Alanine Transaminase / Q000097:blood*; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004796:Clinical Enzyme Tests / Q000379:methods; D004195:Disease Models, Animal; D057775:Ischemic Postconditioning / Q000379:methods; D019194:Ischemic Preconditioning / Q000379:methods; D008099:Liver / Q000098:blood supply* / Q000473:pathology*; D008297:Male; D009336:Necrosis / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D000511:alpha-Macroglobulins / Q000378:metabolism
D015415:Biomarkers; D000511:alpha-Macroglobulins; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase
HPB surgery; experimental animal study; hepatic necrosis; ischaemia/reperfusion injuries; liver