Continuous assessment of intrahepatic metabolism by microdialysis during and after portal triad clamping.

BACKGROUND: Ischemia-reperfusion injury is a major concern with portal triad clamping (PTC) in liver surgery. Microdialysis allows continuous intraoperative monitoring of tissue metabolism in the liver. Our aim was to evaluate the feasibility of microdialysis as a tool to assess the intrahepatic metabolic effects of PTC in patients undergoing liver resection. METHODS: Eleven patients who underwent liver resection were subjected to intrahepatic microdialysis. Dialysis fluid samples were collected before, during, and after a 20-min period of PTC. Glucose, lactate, pyruvate (markers of ischemia), and glycerol (marker of cell membrane damage) were analyzed and the lactate/pyruvate ratio was calculated. RESULTS: During PTC, intrahepatic glucose, lactate, and glycerol increased from 9.1±2.2 to 14.5±2.4 mM, from 2.2±0.3 to 5.8±0.5 mM, and from 63±14 to 142±28 µM, respectively. Pyruvate was unchanged, resulting in an increased lactate/pyruvate ratio (from 39±10 to 104±32). During initial reperfusion, glucose further increased to 16.4±2.9 mM. Pyruvate increased after reperfusion (from 93±18 to 138±23 µM), while lactate was stable, resulting in a normalized lactate/pyruvate ratio. Glycerol continued to increase during initial reperfusion. CONCLUSIONS: PTC was associated with considerable intrahepatic metabolic alterations with anaerobic metabolism, increased glycogenolysis, and cellular membrane damage resulting in increased levels of glucose, lactate, glycerol, and lactate/pyruvate ratio. Microdialysis is easy to use and allows continuous monitoring of intrahepatic metabolism during liver surgery.

Microdialysis monitoring of porcine liver metabolism during warm ischemia with arterial and portal clamping.

Early detection of vascular complications following liver surgery is crucial. In the present study, intrahepatic microdialysis was used for continuous monitoring of porcine liver metabolism during occlusion of either the portal vein or the hepatic artery. Our aim was to assess whether microdialysis can be used to detect impaired vascular inflow by metabolic changes in the liver. Changes in metabolite concentrations in the hepatic interstitium were taken as markers for metabolic changes. After laparotomy, microdialysis catheters were introduced directly into the liver, enabling repeated measurements of local metabolism. Glucose, lactate, pyruvate, and glycerol were analyzed at bedside every 20 minutes, and the lactate/pyruvate ratio was calculated. In the arterial clamping group, the glucose, lactate, glycerol, and lactate/pyruvate ratio significantly increased during the 2-hour vessel occlusion and returned to baseline levels during the 3-hour reperfusion. In the portal occlusion group and in the control group, the measured metabolites were stable throughout the experiment. Our findings show that liver metabolism, as reflected by changes in the concentrations of glucose, lactate, and glycerol and in the lactate/pyruvate ratio, is markedly affected by occlusion of the hepatic artery. Surprisingly, portal occlusion resulted in no major metabolic changes. In conclusion, the microdialysis technique can detect and monitor arterial vascular complications of liver surgery, whereas potential metabolic changes in the liver induced by portal occlusion were not seen in the current study. Microdialysis may thus be suitable for use in liver surgery to monitor intrahepatic metabolic changes.

Hepatic cell membrane damage during cold preservation sensitizes liver grafts to rewarming injury.

BACKGROUND/PURPOSE: Increasing levels of glycerol in extracellular fluid indicate cell membrane disintegration, and can be continuously monitored with microdialysis. The aim of this study was to monitor liver cell membrane damage during liver transplantation in a pig model. METHODS: Thirteen donor and recipient pairs were divided into two groups; group I, with a liver ischemia time of 5 h (n = 6), and group II, with 15 h of ischemia (n = 7). Microdialysis samples from the liver graft were collected at 20-min intervals during donor operation, cold preservation, implantation, and reperfusion in the recipient. Glycerol concentrations were analyzed. RESULTS: During cold preservation, a continuous increase in glycerol levels was observed. This increase correlated with the time of cold ischemia (r2 = 0.88). During implantation, an accelerated increase of glycerol was observed, with a higher acceleration in group II (P < 0.005). During the first hour after reperfusion, a higher release of glycerol was observed in group II (P = 0.0005). CONCLUSIONS: Our data show a constant glycerol release during cold storage, indicating a continuous injury to the cell membranes over time. Improvement in cell membrane protection during cold preservation could lead to improvement in liver transplantation outcome and acceptance of an extended period of cold ischemia.

Intraperitoneal microdialysis (IPM): a new technique for monitoring intestinal ischemia studied in a porcine model.

Acute mesenteric thrombosis, vascular complications of intestinal transplantation, sepsis, and multiple organ failure are all associated with intestinal ischemia. To improve the outcome of these patients, better monitoring devices are needed. A new technique, intraperitoneal microdialysis (IPM), was evaluated for detection of intestinal ischemia in a porcine model, with the intention of evaluating the technique for future use on humans. Fourteen pigs divided into two studies were used. In a total ischemia study a microdialysis catheter was placed intraperitoneally and the superior mesenteric artery was occluded for 1 h 40 min. In a local ischemia study, the arcus vessels supplying a 30-cm long small bowel segment were occluded for 3 h 20 min. One IPM catheter was placed next to the ischemic area and another IPM catheter 10 cm caudally as an intraperitoneal reference. In both studies reference catheters were placed subcutaneously. Glucose, lactate, pyruvate, and glycerol were analyzed every 20 min. In both studies vessel occlusion resulted in decreased glucose and increased lactate, glycerol, and lactate/pyruvate ratio. Significant changes were reached after 60 min of ischemia in most analytes, whereas the values from the reference catheter were stable. Our conclusion is that intestinal ischemia is detectable with IPM based on the analysis of well-documented markers of ischemia (increased lactate/pyruvate ratio) and cell membrane damage (elevated glycerol levels). It allows semi-continuous monitoring of the intestines with a minimally invasive procedure, which we believe will be possible to apply in human routine clinical use.

Metabolic changes in the liver graft monitored continuously with microdialysis during liver transplantation in a pig model.

Microdialysis provides the opportunity to continuously monitor metabolic changes in tissue. The aim of the study is to monitor metabolic changes in the liver graft over time during transplantation in a pig model. Fourteen littermate female pigs with a body weight of 30 to 34 kg were used for seven orthotopic liver transplantations. Intrahepatic implantation of a microdialysis catheter into the liver graft was performed in the donor. Microdialysis samples were collected at 20-minute intervals during the donor operation, cold preservation, and for 7 hours after reperfusion in the recipient. Glucose, lactate, pyruvate, and glycerol concentrations were measured. After cold perfusion, glucose, lactate, and glycerol levels increased, whereas pyruvate levels decreased rapidly. During cold storage, glucose and glycerol levels increased, whereas lactate levels remained stable and pyruvate levels were undetectable. During implantation of the liver graft, glucose, lactate, and glycerol levels showed an accelerated increase. After portal reperfusion, glucose, lactate, and glycerol levels continued to increase for another 40 to 60 minutes, after which they decreased and finally settled at normal levels. At this time, pyruvate levels increased, with a peak within 2 hours after reperfusion, and then decreased to normal levels. Calculated lactate-pyruvate ratio increased after cold perfusion and remained stable during cold storage. During rewarming, it showed an accelerated increase, but after reperfusion, it decreased rapidly. Rewarming and reperfusion are most harmful to the liver, reflected by an accelerated increase in glucose and glycerol levels and lactate-pyruvate ratio. High intrahepatic glucose levels during ischemia appear to be a liver-specific event, which may represent glycogen degradation in injured hepatocytes.