BACKGROUND AND METHODS: Alteration of the hepatocellular function following ischemic damage may play a crucial role in the limited recovery after reperfusion. In spite of numerous efforts, finding a simple technique for predicting recovery of the liver after ischemic damage is still an unresolved problem. During ischemic storage of isolated rat livers at 25 degrees C tissue concentrations of high energy phosphates and lactate were determined photometrically and interstitial pH was measured by glass electrodes. In comparison, the metabolic rate was measured continuously by direct calorimetry. In a second series of experiments these results were compared with functional recovery after ischemia and reperfusion. Following ischemic storage at 25 degrees C for 60, 120 or 240 min, the isolated livers were reperfused for 30 min in a non-recirculating system with a constant flow rate. During reperfusion functional recovery, as assessed by oxygen consumption and bile flow, was determined. At the end of reperfusion tissue samples were taken for biochemical analysis of adenine nucleotides. Furthermore, morphologic integrity was determined by electron microscopy. RESULTS: Whereas the ATP concentration drops within 60 min of ischemia to 6.9% of the control value without further significant change, the continuously measured metabolic rate as assessed by direct calorimetry decreases in an exponential manner. Accordingly, a better correlation of hepatocellular secretory function and calorimetrically measured heat output (r2 = 0.85; P <0.001) was observed than with high energy phosphates (r2 = 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 incomplete or impossible. Therefore, assessment of the global metabolic rate by direct calorimetry seems not only to be a very good predictor of recovery after ischemic damage but also a good tool in the laboratory for studies concerning the sequelae of ischemic metabolism and for improvement of tissue protection.
