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 prolon ged inflow occlusion at normothermic conditions can produce evidence o f reversible or irreversible hepatocellular damage. Cytoprotective age nts have been used both experimentally and clinically to afford extend ed viability of hepatocytes under reduced perfusion. One agent, prosta glandin E(1), has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify th is observation in an experimental model using prolonged normothermic i nflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepat ic artery, choledochal vessels) to allow for sufficient splanchnic dec ompression. Half of the animals received pretreatment with prostagland in E(1) (alprostadil) 500 mu g intravenously. Inflow occlusion was mai ntained for 2 hours followed by reperfusion and killing 24 hours later . As a measure of functional preservation, the tissue adenine nucleoti des adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-perfo rmance liquid chromatography during occlusion and after reperfusion. C ytosolic enzyme determinations (aspartate transaminase, alanine transa minase, lactate dehydrogenase) were also made before occlusion and aft er reperfusion. As a possible indicator of cellular injury, blood ioni zed Ca++ was measured before inflow occlusion and after reperfusion. A lthough no difference was found in levels of AMP and ADP between prost aglandin E(1) and control animals, ATP levels rose significantly highe r during recovery in prostaglandin E(1) animals at 60 minutes and 24 h ours 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 m oles/g dry weight control P < .01). However, energy charge (ATP + 1/2 ADP/ATP ADP + AMP) showed no significant difference between prostaglan din E(1) and control groups at any time measured. There also was no si gnificant difference in cytosolic enzymes or blood ionized Ca++ levels between prostaglandin El and control animals. We conclude pretreatmen t with prostaglandin E(1) facilitates recovery of ATP on reperfusion a fter normothermic hepatic ischemia. The mechanism for this phenomenon remains unclear but does not seem to involve transcellular Ca++ flux M ore rapid recovery of ATP may allow for continued viability of margina lly damaged hepatocytes.