Atsuhiko Maki

Response of hepatic mitochondrial redox state to oral glucose load. Redox tolerance test as a new predictor of surgical risk in hepatectomy.

The redox tolerance test introduced in this article attempts to quantify the deterioration of hepatic mitochondrial energy metabolism by measuring the changes in arterial ketone body ratio in response to 75-g oral glucose loading, and is discussed in relation to its predictive value for assessing surgical risk in hepatectomy. The indicator, called redox tolerance index (RTI), represents a 100-fold cumulative enhancement of ketone body ratio relative to glucose level (100 x delta KBR/delta glucose). The redox tolerance index was significantly different between 31 liver cirrhotics and 10 normal volunteers (p less than 0.001). Subjects were divided into three classes (I: RTI greater than or equal to 1.0, II: 0.5 less than or equal to RTI less than 1.0, III: RTI less than 0.5). Postoperative mortality was significantly different among the three classes in 127 hepatic resections (chi 2 = 9.843, p less than 0.01). Of 97 hepatocellular carcinoma cases, major hepatic resections in class III showed significantly higher postoperative morbidity and mortality rates (p less than 0.05 and p less than 0.05, respectively). The present findings indicate that RTI based on redox theory is of potential value in predicting posthepatectomy outcome.

Determination of cytochromes in human liver contaminated with hemoglobin

A spectrophotometric method was developed to determine cytochromes in human liver mitochondria contaminated with hemoglobin. The influence of hemoglobin on the measurement was canceled by keeping hemoglobin in the carbon monoxide bound form throughout determination. Mitochondria were solubilized by 2% sodium cholate, and cytochromes were reduced enzymatically with glutamate and succinate as substrates to the maximal extent. The amount of cytochromes determined spectrophotometrically was linearly correlated with mitochondrial protein at least up to the extent of 8 mg/ml.

Influence of piecemeal necrosis on the compensatory increase of mitochondrial respiratory enzymes of the tumour‐bearing liver: Clinical study of 53 surgical cases

The relationships between histological findings, adaptively increased cytochrome a(+a3) levels in chronic liver disease and complications after hepatectomy were studied in order to clarify the mechanism of mitochondrial derangement. The liver specimens of 53 hepatectomized patients were randomly evaluated by three independent hepatopathologists and were compared with cytochrome a(+a3) levels in the biopsied liver, the extent of operation and postoperative complications.

Orthotopic partial liver transplantation in dogs can be performed without cold perfusion of the donor liver: evaluation of its feasibility in terms of energy metabolism

To investigate the feasibility of obtaining grafts from living, genetically related adult donors without any complicated harvesting techniques, orthotopic partial liver transplantation (PLT) without cold perfusion of the donor graft was evaluated in beagles by assessing the graft viability using ketone body ratio (KBR). Ten PLT were performed under venovenous bypass. The left half of the donor liver was transected in situ followed by systemic heparinization, and immediately implanted with care taken to leave the recipients inferior vena cava intact, and to maintain the normothermic state without cold perfusion. Four of ten dogs survived for 5 days or longer (longest survival was 9 days) and died of other causes than graft dysfunction. Four others died of thromboembolitic episode, accidental bleeding or technical failure. Two dogs died of graft dysfunction. The changes in KBR in 5 dogs without fatal complications after transplantation were maintained within normal range thereafter. These results suggest that the PLT without cold perfusion of donor graft is possible from the viewpoint of energy metabolism.

Changes in Serum Bile Acid Composition in Relation to Histological Findings after Liver Transplantation in Piglets

Changes in the composition of serum bile acids were investigated after orthotopic liver transplantation in piglets. Serum levels of all bile acid components rapidly increased during the anhepatic phase and then quickly decreased, returning to the preoperative state within 6 h of revascularization of the allograft. In the animals in which extrahepatic biliary stenosis was a complication, serum total bile acids (TBA) increased remarkably. A marked increase of hyocholic acid and marked decrease of hyodeoxycholic acid were noted; as percentages of TBA, the average levels per day were 91.3 +/- 1.3 and 5.0 +/- 1.3%, respectively. No change in chenodeoxycholic acid (CDCA) was observed. In the animals suffering acute rejection without extrahepatic biliary stenosis, serum TBA increased slightly and the percentage of CDCA rose, the average level being 29.6 +/- 1.5%. These results suggest that the measurement of the composition of serum bile acids may serve as a useful means of assessing allograft function after liver transplantation.