THE EFFECT OF PROSTAGLANDIN E(1) ON LIVER ADENINE-NUCLEOTIDES AND CYTOPLASMIC ENZYMES IN A PORCINE MODEL OF NORMOTHERMIC HEPATIC ISCHEMIA

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E(1), has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E(1) (alprostadil) 500 mu g intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E(1) and control animals, ATP levels rose significantly higher during recovery in prostaglandin E(1) animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mu moles/gm dry weight prostaglandin E(1) vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mu moles/g dry weight control P < .01). However, energy charge (ATP + 1/2 ADP/ATP ADP + AMP) showed no significant difference between prostaglandin E(1) and control groups at any time measured. There also was no significant difference in cytosolic enzymes or blood ionized Ca++ levels between prostaglandin El and control animals. We conclude pretreatment with prostaglandin E(1) facilitates recovery of ATP on reperfusion after normothermic hepatic ischemia. The mechanism for this phenomenon remains unclear but does not seem to involve transcellular Ca++ flux More rapid recovery of ATP may allow for continued viability of marginally damaged hepatocytes.