The Beneficial Effect of Dibutyryl Cyclic Adenosine Monophosphate on Warm Ischemic Injury of the Rat Liver Induced by Cardiac Arrest1

Abstract

Dibutyryl cAMP (DBcAMP) has a high membrane permeability, and maintenance of the intracellular cAMP concentration may improve the viability of organs. In this study, the effect of DBcAMP pretreatment on warm ischemic injury of rat livers was evaluated. Warm ischemic liver injury was induced in adult Wistar rats weighing 250-280 g by leaving them at room temperature (22-25 degrees C) after cardiac arrest. The hepatic cAMP concentration, %ATP, and trypan blue-positive nuclear ratio were determined after different durations of warm ischemia. In addition, transaminase and endothelin-1 (ET-1) release into the perfusate were examined during 60 min of isolated liver perfusion with Krebs-Henseleit solution. The optimal dose and time of DBcAMP pretreatment were determined to be 15 mg/kg and 60 min prior to warm ischemia, respectively. Data on the trypan blue-positive nuclear ratio and the release of transaminases and ET-1 revealed that warm ischemia first damaged the endothelial cells and then the hepatocytes. DBcAMP pretreatment appeared to protect the liver from warm ischemic injury by increasing the intracellular cAMP concentration and stabilizing the cell membranes of endothelial cells and hepatocytes.

Dynamic Changes of Post-Ischemic Hepatic Microcirculation Improved by a Pre-Treatment of Phosphodiesterase-3 Inhibitor, Milrinone

“…Here selective inhibition of cAMP phosphodiesterase resulted in elevated cAMP concentration. During partial warm ischemia of the liver, energy-rich phosphates degrade very rapidly and consequently the synthesis of cAMP is declined [32]. In this condition, the influence of phosphodiesterase inhibition on intracellular cAMP- sparing activity may be conspicuous and effective.…”

The Effect of Amrinone on Liver Regeneration in Experimental Hepatic Resection Model1

“…Increased intracellular cAMP concentration has protective effects, improving hepatocyte and endothelial cell membrane stability for liver [33]. Intracellular cAMP concentration increases with adenylate cyclase enzyme activity and decreases with phosphodieasterase enzyme activity [6,7].…”

Adenosine A2 receptor stimulation protects the predamaged liver from cold preservation through activation of cyclic adenosine monophosphate-protein kinase a pathway

“…A central role of cAMP in protecting the ischemic liver graft is corroborated by other studies showing that endogenous or exogenous elevation of hepatic cAMP signal is associated with improved liver viability in NHBDs. 11,20 As well as its ability to activate PKA, cAMP may have a role in organ preservation by counteracting excessive accumulation of intracellular calcium. It inhibits the formation of a calcium-calmoduline complex, 21 which is likely to result in mitochondrial and cellular membrane dysfunction because of a deleterious impact on the phospholipid moiety of these structures.…”