Effect of remote ischemic preconditioning on liver ischemia/reperfusion injury using a new mouse model.
Ischemic preconditioning of remote organs (RIPC) reduces liver ischemia/reperfusion (IR) injury in the rabbit and rat. Mice are the only species available with a large number of transgenic strains. This study describes development and validation of a mouse model of hindlimb RIPC that attenuates liver IR injury. Mice were allocated to 4 groups: (1) Sham surgery; (2) RIPC: 6 cycles of 4 × 4 minutes ischemia/reperfusion of hindlimb; (3) IR: 40 minutes lobar (70%) hepatic ischemia and 2 hours reperfusion; (4) RIPC+IR: RIPC followed by IR group procedures. Plasma liver aminotransferases and hepatic histopathological and transmission electron microscopy studies were performed at the end of the experiment. Hepatic microcirculatory blood flow was measured throughout the experiment. Postoperative complications and animal survival were evaluated. Hindlimb RIPC using a tourniquet resulted in limb paralysis. Hindlimb RIPC using direct clamping of the femoral vessels showed no side effects. Compared to liver IR alone, RIPC+IR reduced plasma aminotransferases (P < 0.05) and histopathological and ultrastructural features of injury. Hepatic microcirculatory blood flow was preserved in the RIPC+IR compared to IR group (P < 0.05). There was no mortality in any of the groups. By demonstrating a consistent improvement in these features of liver IR injury with antecedent hindlimb RIPC and by minimizing experimental confounding variables, we validated this mouse model. In conclusion, we describe a validated mouse model of hindlimb RIPC that reduces liver IR injury. With the availability of transgenic mice strains, this model should prove useful in unraveling the mechanisms of protection of hindlimb RIPC.
Division of Surgery and Interventional Science, University College London, United Kingdom.
Mahmoud
M
Abu-Amara
Shi Yu
SY
Yang
Alberto
A
Quaglia
Peter
P
Rowley
Niteen
N
Tapuria
Alexander M
AM
Seifalian
Barry J
BJ
Fuller
Brian R
BR
Davidson
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003250:Constriction; D004195:Disease Models, Animal; D006614:Hindlimb; D019194:Ischemic Preconditioning / Q000009:adverse effects; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000648:ultrastructure; D008102:Liver Circulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D046529:Microscopy, Electron, Transmission; D018482:Muscle, Skeletal / Q000098:blood supply*; D010243:Paralysis / Q000209:etiology; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D015203:Reproducibility of Results; D013997:Time Factors; D014111:Tourniquets
D015415:Biomarkers; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase