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Ischaemic preconditioning of the liver: a preliminary study
K J Hardy1, D N McClure, S Subwongcharoen
1Department of Surgery, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australian.
Background:
A phenomenon of 'preconditioning' exists for the heart, but has not been described for the liver. This study was undertaken to determine whether a brief episode of ischaemia (3 or 5 min) followed by a short reperfusion time (5 or 10 min) would precondition the liver to reduce subsequent injury from prolonged ischaemia (30 to 90 min).
Methods:
Male Wistar rats were allocated into five control (no preconditioning) and five preconditioned groups, each having a liver resection. The preconditioning times were 3 min ischaemia followed by 5 min reperfusion with a prolonged ischaemia of 60 or 90 min for the first two groups, and 5 min ischaemia followed by 10 min reperfusion with prolonged ischaemia times of 30 or 45 min for the other three groups.
Results:
Of rats resected with 3-5-60 min time sequence designed to assess survival, 9/10 died. However 9/10 died also in the matching control group with 60 min ischaemia. With a 5-10-45 min sequence, 9/10 survived more than 24 h in the preconditioned group and 1/10 in the non-preconditioned controls. With a 5-10-30+ sequence designed to measure liver function tests, the prothrombin time was significantly improved; bilirubin, serum alkaline phosphatase and the alanine aminotransferase improved but these did not reach significance.
Conclusion:
A brief episode of ischaemia followed by an episode of reperfusion before a prolonged period of ischaemia ameliorated the effects of ischaemia-reperfusion injury in a rat liver resection model. If hepatic preconditioning is confirmed in humans, ischaemic preconditioning will have an important role for all liver surgery.