Introduction: Conditioning of liver grafts by bolus pretreatment with prostaglandins has been previously demonstrated to improve hepatic bile flow. However, the underlying mechanisms have not been investigated. To elucidate whether improved bile flow after prolonged ischemia is due to maintained bile acid secretion or due to increased paracellular permeability, we performed a study using increasing doses of the marker acid taurocholate in the isolated perfused rat liver system.
Methods: Livers were harvested from adult Lewis rats and stored for 24 hours in UW solution. Pretreatment of livers was performed 1 minute before preservation. One group received prostaglandin I2, the second group received prostaglandin E1, and the control group was treated with saline. After 24 hours of cold storage the grafts were investigated in the isolated perfused rat liver system by perfusion with an oxygenated Krebs-Ringer-Henseleit buffer. Increasing doses of the radiolabeled marker bile acid taurocholate were infused to investigate bile acid transport.
Results: Bile flow and bile acid output were increased by pretreatment of the livers with prostaglandin I2 and prostaglandin E1, as compared to the control group. More specifically, the maximum transport rate was tripled by prostaglandin I2 and by prostaglandin E1 preconditioning of liver grafts, in comparison to the control group (P < .01 vs prostaglanin I2 and E1).
Conclusion: The results clearly demonstrate that increased bile flow after conditioning of liver grafts with prostaglandins is not due to increased paracellular permeability but is based on markedly improved bile acid output.