Modulation of microcirculatory changes in the late phase of hepatic ischaemia-reperfusion injury by remote ischaemic preconditioning.
BACKGROUND
Remote ischaemic preconditioning (RIPC) is a novel method of protecting the liver from ischaemia-reperfusion (I-R) injury. Protective effects in the early phase (4-6 h) have been demonstrated, but no studies have focused on the late phase (24 h) of hepatic I-R. This study analysed events in the late phase of I-R following RIPC and focused on the microcirculation, inflammatory cascade and the role of cytokine-induced neutrophil chemoattractant-1 (CINC-1).


METHODS
A standard animal model was used. Remote preconditioning prior to I-R was induced by intermittent limb ischaemia. Ischaemia was induced in the left and median lobes of the liver (70%). The animals were recovered after 45 min of liver ischaemia. At 24 h, the animals were re-evaluated under anaesthesia. Hepatic microcirculation, sinusoidal leukocyte adherence and hepatocellular death were assessed by intravital microscopy, hepatocellular injury by standard biochemistry and serum CINC-1 by enzyme-linked immunosorbent assay (ELISA).


RESULTS
At 24 h post I-R, RIPC was found to have improved sinusoidal flow by increasing the sinusoidal diameter. There was no effect of preconditioning on the velocity of red blood cells, by contrast with the early phase of hepatic I-R. Remote ischaemic preconditioning significantly reduced hepatocellular injury, neutrophil-induced endothelial injury and serum CINC-1 levels.


CONCLUSIONS
Remote ischaemic preconditioning is amenable to translation into clinical practice and may improve outcomes in liver resection surgery and transplantation.
Hepatopancreatobiliary and Liver Transplant Unit, Department of Surgery, Royal Free Hospital, University College London, London, UK. ntapuria@yahoo.com
Niteen
N
Tapuria
Sameer
S
Junnarkar
Mahmoud
M
Abu-Amara
Barry
B
Fuller
Alexander M
AM
Seifalian
Brian R
BR
Davidson
D000818:Animals; D001783:Blood Flow Velocity; D002448:Cell Adhesion; D016923:Cell Death; D054360:Chemokine CXCL1 / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006614:Hindlimb / Q000098:blood supply*; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014111:Tourniquets
D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat