Addition of a kidney to the normothermic ex vivo perfused porcine liver model does not increase cytokine response

Abstract

The addition of a kidney to the ex vivo liver perfused model may facilitate the circuit homeostatic balance of important biochemical parameters (i.e. pH changes, urea and creatinine, or glucose levels) but might also increase the inflammatory reaction produced. In this study, we compared the production of various cytokines between liver-kidney and liver-alone circuits. Seven livers were harvested from female pigs and perfused for 6 h. In five additional experiments, a kidney was also harvested and connected in parallel. Blood samples for interleukins (IL) 1, 2, 4, 6, 8, 10, and 12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were collected before perfusion and at hours 1, 2, 4 and 6 postperfusion. In the combined liver-kidney circuit, a significant increase was present only for IL-6 and IL-8, but this did not differ significantly from those recorded in the liver-alone circuit. All other cytokines were not modified from baseline levels. The addition of a kidney to the perfusion circuit does not stimulate a greater inflammatory reaction than that of the liver alone and therefore further confirms the safety of the experimental setups in view of more delicate experiments requiring strict homeostatic conditions.

The “kidney–liver” multiorgan ex vivo perfused model improves the circuit’s biochemical milieu during perfusion compared to the “liver–kidney” counterpart

“…The hypothesis that a filtering organ could have better improved the blood biochemical status of the perfusions has been confirmed by the addition of a kidney to our ex vivo porcine hepatic perfusion, creating the first multiorgan ex vivo perfusion set [17]. Results confirmed this hypothesis as the kidney worked by removing the excess potassium, glucose and hydrogen ions [17,18]. Furthermore, the second organ did not stimulate an increased inflammatory reaction to that already demonstrated in the liver perfusions alone [18].…”

“…Results confirmed this hypothesis as the kidney worked by removing the excess potassium, glucose and hydrogen ions [17,18]. Furthermore, the second organ did not stimulate an increased inflammatory reaction to that already demonstrated in the liver perfusions alone [18].…”

“…Although the ex vivo multiorgan circuit resolved part of the limitations encountered with the single organ model the kidney was added to the circuit after 30 min from the hepatic perfusion [17,18]. This left the liver without purification in the initial period.…”

“…These experiments aim to provide a metabolically appropriate environment to the liver since the start of the hepatic perfusion. Results were compared with experiments in which the kidney followed the liver perfusion as previously described [17,18].…”

Steps for the Autologous <em>Ex vivo</em> Perfused Porcine Liver-kidney Experiment

“…Stable blood sugar levels and acid base balance are crucial when studying islet auto-transplantation, especially in the early implantation phase. We have developed a new model incorporating the kidney to clear excess metabolites and improve the environment for the islet transplantation 6,7 .…”