Ischemic preconditioning protects the pig liver by preserving the mitochondrial structure and downregulating caspase-3 activity.
BACKGROUND
The beneficial effects of ischemic preconditioning (IPC) on hepatic ischemia-reperfusion injury (I/RI) have been described. However, the way in which IPC causes the changes in mitochondrial ultrastructure seen in hepatic I/RI is not well understood.


OBJECTIVE
The objective of the present study was to determine whether IPC protects the liver from changes in mitochondrial structure and caspase 3 activity in the early phase of post-ischemic injury.


METHODS
A pig model consisting of 90 min of hepatic ischemia and 180 min of reperfusion was employed. Eighteen female pigs were randomly divided into three groups: sham-operated, non-preconditioned, and ischemic preconditioned (10 min ischemia followed by 10 min reperfusion). Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and thiobarbituric acid reactive substances (TBARS), as well as bile flow, were measured. Liver biopsies were taken after reperfusion for histological, immunohistochemical (anti-caspase 3), and ultrastructural examinations.


RESULTS
The IPC procedure increased bile flow (p < 0.01), reduced serum AST level (p < 0.01), and reduced serum concentration of TBARS at 180 min of reperfusion (p = 0.05). Ischemic-preconditioned liver cells had less caspase 3 activity than the non-preconditioning group (p < 0.01), and changes in mitochondrial ultrastructure were reduced (p < 0.01).


CONCLUSIONS
IPC exerts a powerful protective effect against hepatic I/RI in the early phase of reperfusion, which may be mediated by preservation of mitochondrial structure and inhibition of caspase-3 activity.
Giovanardi
Rafael Omar
RO
Department of Surgery, University of Caxias do Sul (UCS), Caxias do Sul, RS, Brazil. rafaelgiovanardi@hotmail.com
Rhoden
Ernani Luis
EL
Cerski
Carlos Thadeu
CT
Salvador
Miriam
M
Kalil
Antonio Nocchi
AN
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects*; D008933:Mitochondrial Swelling / Q000502:physiology; D034421:Sus scrofa; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3