Prediction of recovery after ischemia. A microcalorimetric and biochemical study of rat liver tissue

Abstract 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 the recovery of the liver after ischemic damage is still an unresolved problem. During the ischemic storage of isolated rat livers at 25°C, tissue concentrations of high energy phosphates, glycogen and lactate were determined photometrically and, in comparison, the metabolic rate was measured continuously by direct calorimetry. In addition, interstitial pH was measured with microelectrodes. In a second series of experiments these results were compared with functional recovery after ischemia and reperfusion. Following ischemic storage at 25°C for 60, 120 and 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 and tissue lactate. Though the ATP concentration drops within 60 min of ischemia to 6.94% of the control value without further significant change, the metabolic rate measured continuously by direct calorimetry decreases in an exponential manner. According to the calorimetrically measured heat output, functional hepatic metabolism, as assessed by oxygen consumption, bile flow and restoration of high energy phosphates during reperfusion, recovered to an extent depending on the duration of ischemia. It is concluded that the metabolic rate of the ischemic rat liver, as determined continuously by direct calorimetry, is a good predictor for recovery after ischemic damage.