In vivo subcellular elemental dynamics in liver graft: With special reference to effect of non-selective endothelin receptor antagonist, TAK-044, on the graft injury

Background: No data are available concerning the in vivo subcellular dynami cs of elements in liver grafts and the effect of endothelin receptor antago nist, TAK-044, against graft injury. Methods: Liver transplantation was per formed in porcine under active veno-venous bypass. The grafts stored in chi lled preservation solution were recirculated following reflush with lactate d Ringer's solution with or without TAK-044 (10 mg/kg). Cold and warm ische mic times of the grafts were comparable between the two groups. Elements (N a, K. Cl, Ca, P and S) were measured in three fractions of cytoplasm, mitoc hondria and nucleus by electron probe X-ray microanalysis for the graft bio psy specimens obtained at various time from donor laparotomy to 1 week afte r liver grafting. Liver functions also were compared between the two groups . Results: In both groups, concentration of each element changed in paralle l among the three subcellular fractions and their changes were less marked in the nucleus. In the control group, there were significant increases in c ytoplasmic Na and Cl after portal reperfusion and ill cytoplasmic and mitoc hondrial Ca after hepatic artery reperfusion. These were accompanied by K a nd mitochondrial S decreases without; a statistical significance. In the TA K group, such postreperfusion elemental alterations were significantly supp ressed and early deterioration of the liver functions was alleviated, as co mpared with the control group. Conclusion: A supplemental use of TAK-044 in a rinse solution before reflush contributed to stability of subcellular el ements after reperfusion and better preservation of early graft function. ( C) 2000 Elsevier Science Ireland Ltd. All rights reserved.