Interstitial Accumulation of Na+ and K+ During Flush–Out and Cold Storage of Rat Livers: Implications for Graft Survival

Abstract

Intracellular–type electrolyte solutions were introduced into organ preservation to prevent K⁺ efflux and Na⁺ and Cl^- influx into cells and cell swelling during cold ischemia. We studied cation accumulation in the interstitial space by microdialysis, during rat liver cold storage and after flush–out with high–K⁺ and low–K⁺ solutions. The effect of Na⁺ and K⁺ on graft function and survival was studied in an isolated perfused liver model and an orthotopic transplantation model after rat liver storage in iso–osmolar high–K⁺ and low–K⁺ solutions. After 24 hours of cold ischemia [Na⁺]_o dropped from 136 ± 2 mmol/L to 91.8 ± 1.1 mmol/L, and [K⁺]_o increased from 5.9 ± 0.1 mmol/L to 12.2 ± 1.6 mmol/L (P < .001 vs. control). [Na⁺]_o and [K⁺]_o after flush–out did not equilibrate with [Na⁺]_sol and [K⁺]_sol after 24 hours of cold storage. Rat livers preserved in low–K⁺ solutions produced significantly more bile during isolated reperfusion and released less alanine transaminase, aspartate transaminase, and lactate dehydrogenase into the reperfusion medium than high–K⁺ solutions. Rat liver survival after 14 hours of preservation was higher in low–K⁺ solutions (13 of 13) than in high–K⁺ solutions (7 of 13). Those studies indicate that during cold storage of rat livers, transmembraneous Na⁺–K⁺ sodium–potassium exchange might not follow the 3:2 stochiometry of a sole sodium–potassium exchange via Na⁺–K⁺ sodium–potassium adenosine triphosphatase (ATPase), and that low–K⁺ solutions might improve graft function and survival after rat liver preservation.