HIGH-ENERGY PHOSPHATES AND DIRECT CALORIMETRY AS PREDICTIVE PARAMETERS FOR METABOLIC RECOVERY OF THE RAT-LIVER FOLLOWING ISCHEMIA

Background and Methods: Alteration of the hepatocellular function foll owing ischemic damage may play a crucial role in the limited recovery after reperfusion. In spite of numerous efforts, finding a simple tech nique for predicting recovery of the liver after ischemic damage is st ill an unresolved problem. During ischemic storage of isolated rat liv ers at 25 degrees C tissue concentrations of high energy phosphates an d lactate were determined photometrically and interstitial pH was meas ured by glass electrodes. In comparison, the metabolic rate was measur ed continuously by direct calorimetry. In a second series of experimen ts these results were compared with functional recovery after ischemia and reperfusion. Following ischemic storage at 25 degrees C for 60, 1 20 or 240 min, the isolated livers were reperfused for 30 min in a non recirculating system with a constant flow rate. During reperfusion fun ctional recovery, as assessed by oxygen consumption and bile flow, was determined. At the end of reperfusion tissue samples were taken for b iochemical analysis of adenine nucleotides. Furthermore, morphologic i ntegrity was determined by electron microscopy. Results: Whereas the A TP concentration drops within 60 min of ischemia to 6.9% of the contro l value without further significant change, the continuously measured metabolic rate as assessed by direct calorimetry decreases in an expon ential manner. Accordingly, a better correlation of hepatocellular sec retory function and calorimetrically measured heat output (r(2)=0.85; P<0.001) was observed than with high energy phos phates (r(2)=0.56; P< 0.001). Conclusions: These data suggest that if the metabolism of the ischemic rat liver falls below a critical level, recovery is incomplet e or impossible. Therefore, assessment of the global meta belie rate b y direct calorimetry seems not only to be a very good predictor of rec overy after ischemic damage but also a good tool in the laboratory for studies concerning the sequelae of ischemic metabolism and for improv ement of tissue protection.