K. Vanness et al., DIBUTYRYL-CAMP REDUCES NONPARENCHYMAL CELL-DAMAGE DURING COLD PRESERVATION OF RAT LIVERS, The Journal of surgical research, 58(6), 1995, pp. 728-731
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.