ADENOSINE DEAMINASE INHIBITION ATTENUATES REPERFUSION LOW FLOW AND IMPROVES GRAFT SURVIVAL AFTER RAT LIVER TRANSPLANTATION1

Abstract

Background. Low flow or no flow is a prefinal step after reperfusion of hepatic allografts. Adenosine is an intrinsic key regulator of physiological and pathological hepatic blood flow. Methods. In a model of rat liver transplantation, the effect of donor pretreatment with adenosine deaminase inhibitors (0, 0.1, 1, 10 μmol erythro-9-[2-hydroxy-3-nonyl]adenine) was studied on hepatic interstitial adenosine concentrations, microcirculatory flow, leukocyte adhesion, and graft survival by means of microdialysis sampling, intravital video microscopy, and laser Doppler flowmetry. Results. Donor pretreatment with 1 μmol erythro-9-[2-hydroxy-3-nonyl]adenine increased interstitial adenosine concentrations 5- to 10-fold, for more than 24 hr of cold storage. In LDF studies, mean donor blood flow was increased from 420±42 perfusion units (PU) to 832±52 PU and from 475±79 to 720±81 PU after reperfusion, and in intravital video microscopy studies from 247±24 to 281±39 pl/sec. There was no difference in the number of leukocytes sticking, but a significantly lower percentage of leukocytes rolling (26.1±1.9 vs. 36.5±7.5%) along the endothelial wall in the treatment group. Transplant survival after 44 hr cold storage in UW solution was 8/10 in the treatment group and 1/13 in the control group. Conclusions. Donor pretreatment with erythro-9-[2-hydroxy-3-nonyl]adenine increases survival of critically injured liver grafts. Donor or recipient treatment rather than addition of protectants to cold storage solutions are successful strategies to overcome preservation injury and possibly adverse donor factors.