DIBUTYRYL-CAMP REDUCES NONPARENCHYMAL CELL-DAMAGE DURING COLD PRESERVATION OF RAT LIVERS

Sinusoidal lining cells are the main target for cold preservation inju ry and are further damaged with reperfusion. Different agents known to increase intracellular cAMP levels have been shown beneficial. This s tudy was designed to assess the possible protective effect of a cAMP a nalogue on nonparenchymal cells of rat livers, during cold storage and during reperfusion. Parameters reflecting the status of the liver mic rovasculature were analyzed. The initial effluent collected after pres ervation reflects release during the cold storage period; therefore we measured interleukin-1 (IL-1) and endothelin-1 (ET-1) levels in these samples in order to detect and quantitate the degree of activation an d/or disruption of Kupffer and sinusoidal endothelial lining cells. Ra t livers were harvested after in situ flush with Ringer's lactate with or without 2 mM dibutyryl cAMP, excised, and stored in the same solut ion at 4 degrees C. After 6 hr, livers were perfused with Krebs-Hensel eit buffer for 90 min. Physiological parameters were monitored through out the perfusion. Perfusate samples were collected every 30 min for R IA measurements of IL-1 and ET-1. Treatment resulted in a significant decrease in release of ET-1 and IL-1 during storage. Likewise, livers treated with cAMP had a significantly improved bile output and decreas ed portal vein resistance during reperfusion. The beneficial effect gr anted by the analogue during cold storage and reperfusion was evident on parenchymal and nonparenchymal cells. Levels of ET-1 and IL-1 in th e caval effluent confirm and quantitate preservation damage. (C) 1995 Academic Press, Inc.