Masashi Noguchi

Short-term changes in blood ketone body ratio in the phase immediately after liver transplantation

Arterial blood ketone body ratio was measured after orthotopic liver transplantation in piglets. Ketone body ratio immediately decreased at the beginning of the anhepatic phase and was rapidly restored to the normal levels within 30 min after the revascularization of the allograft. Serum lactate and pyruvate levels increased in anhepatic phase and gradually decreased after revascularization. Changes in the lactate and pyruvate levels were always preceded by changes in ketone body ratio. In the case of transplantation after 12-hr-preservation of the allograft, ketone body ratio failed to maintain normal levels after transplantation, resulting in a high mortality. It is suggested that the elevation of decreased ketone body ratio is prerequisite for the normalization of the deranged metabolic state after liver transplantation, and that ketone body ratio provides an accurate means to assess the initial metabolic function of the allograft.

Presacral epidermal cyst found in an adult male with a high CEA content: Report of an unusual case

A 63-year-old Japanese man presented with constipation, having noticed flat stools for several years. Digital examination of the rectum, followed by barium enema, colonofiberscopy, computed tomography (CT), and magnetic resonance imaging (MRI) revealed an oval mass located between the retrorectal and presacral space without any mucosal lesion. This mass had narrowed the rectal lumen by compressing the rectum anteriorly. Although the plasma levels of the tumor markers were within the normal range, those of the tumor contents were elevated with a carcinoembryonic antigen (CEA) of 118 ng/mL, while the alpha-fetoprotein (AFP) value was 1 ng/mL. The tumor was completely extirpated through an abdominal incision, and there has been no evidence of recurrence thus far. Histological examination showed that the tumor wall was made of keratinized stratified squamous epithelium without any cutaneous adnexal structure, and hence it was diagnosed as an epidermal cyst. CEA was identified in these benign epithelial cells by immunoperoxidase staining using a monoclonal antibody. To the best of our knowledge, there have been only four other cases with a presacral epidermal cyst documented in the Japanese literature, all of whom were female. Our patient is the first reported case of an adult male with a presacral epidermal cyst.

Changes in Energy Metabolism of Allografts after Liver Transplantation

To evaluate the function of energy metabolism in allografts after liver transplantation, changes in hepatic energy charge levels, oxidative and phosphorylative activities of mitochondria and arterial blood ketone body ratio (acetoacetate/3-hydroxybutyrate; KBR) were studied in piglets. Hepatic energy charge levels decreased to 0.831 +/- 0.010 at 3 days and 0.836 +/- 0.009 at 3 weeks after operation compared to the preoperative value of 0.868 +/- 0.006 (p less than 0.01), and returned to 0.856 +/- 0.007 at 6 weeks. Mitochondrial oxidative and phosphorylative activities were moderately enhanced to 19.14 +/- 2.07 (10(-10) mol ATP/mg of mitochondrial protein/s) at 3 days and 20.89 +/- 1.72 at 3 weeks compared to the preoperative value of 16.74 +/- 2.36, and returned to 16.65 +/- 1.54 at 6 weeks. There was no significant difference in the concentrations of mitochondrial respiratory components, except in cytochrome c + c1. KBR decreased immediately at the beginning of the anhepatic phase and rapidly recovered to the preoperative level within 60 min after revascularization of allografts. There was no change in KBR during the postoperative course except in cases with clinical deterioration. From these results, it is suggested that the mitochondrial capacity for ATP synthesis was enhanced to compensate for the decreased energy charge level and that a decreased KBR is a sign of a critically deranged metabolic function in allografts.

The Influence of Hemodilution in Normal and Cirrhotic Rats in Relation to Hepatic Energy Metabolism

The effects of acute hemodilution on hepatic energy status were compared between carbon-tetrachloride-induced cirrhotic rats and normal rats, using arterial blood ketone body ratio and hepatic energy charge as indices. Arterial blood was withdrawn and replaced with rat plasma in hemodiluted rats and with whole blood in sham-diluted control rats. In normal rats, arterial blood ketone body ratio and energy charge level at 6 hours after hemodilution decreased when the hematocrit value was less than 15%. In contrast, the values decreased at an even higher hematocrit level in cirrhotic rats. It was suggested from these results that the hemodilution procedure exerts a more profound hypoxic effect at a milder hemodilution on a cirrhotic liver than on a normal liver.

Influence of Hemodilution on Hepatic Energy Metabolism in Rat

The effects and safety limits of acute hemodilution on hepatic energy status were investigated in relation to arterial blood ketone body ratio and hepatic energy charge in a hemodilution rat model. As long as the hematocrit value was maintained above 20%, ketone body ratio and energy charge level at 6 h after hemodilution remained at the same levels as those of the sham-diluted groups. However, when hematocrit value was less than 15%, the ketone body ratio markedly decreased from the control value of 0.686 +/- 0.044 to 0.278 +/- 0.048 (p less than 0.001), and energy charge decreased from the control value of 0.856 +/- 0.012 to 0.0806 +/- 0.011 (p less than 0.01). From these results, it was suggested that hemodilution exerts no influence on the energy status of the liver as long as hematocrit is maintained above 20%.

Biological significance of enhanced mitochondrial ketogenesis during the early stages after 70% hepatectomy in rats

Ketogenic capacity of mitochondria from the remnant liver of 70% hepatectomized rats was studied in relation to mitochondrial phosphorylative activity. Ketogenic capacity increased to a maximum of 6.04 +/- 0.39 from 3.84 +/- 0.13 of control, with an enhancement of mitochondrial phosphorylative activity 6 hr after hepatectomy, and then decreased to normal levels within 24 hr. Adenylate energy charge, (ATP + 1/2ADP)/(ATP + ADP + AMP), of the remnant liver decreased to 0.825 +/- 0.006 as compared to 0.849 +/- 0.002 of control 6 hr after operation. At 12 hr, total ketone body concentrations of the arterial blood increased concomitant with a fall in ketone body ratio (acetoacetate/3-hydroxybutyrate) which reflects the decreased liver mitochondrial redox (NAD+/NADH) state. These findings suggest that an enhancement of mitochondrial fatty acid oxidation and ketogenesis occurs concomitant with an enhancement of mitochondrial phosphorylative activity in the remnant liver in response to a decreased energy charge after 70% hepatectomy.

The Influence of Hemodilution in Normal and Hepatectomized Rats in Relation to Hepatic Energy Metabolism

ABSTRACT: The effects and safety limits of acute hemodilution on hepatic energy status were determined by comparison of arterial blood ketone body ratio (acetoacetate/3-hy-droxybutyrate) and hepatic energy charge levels in 70% hepatectomized rats and nonhepatectomized rats. Arterial blood was withdrawn and replaced with rat plasma in hemodiluted rats and with whole blood in sham-diluted control rats. The arterial blood ketone body ratio at 6 hours after hemodilution in hepatectomized and sham-diluted rats (0.454 ± 0.037) was lower than that of nonhepatectomized and sham-diluted rats (0.686 ± 0.044). In hepatectomized groups, it decreased to 0.403 ± 0.043 when the hematocrit value was less than 20% and to 0.286 ± 0.031 when it was less than 15%. In hepatectomized rats, hepatic energy charge at 6 hours after hemodilution was 0.809 ± 0.021 in sham-diluted controls, but decreased to less than 0.8 when the hematocrit was less than 20%. On the other hand, in nonhepatectomized rats, the energy charge was greater than 0.8 even when the hematocrit was less than 15% These results suggest that hemodilution procedure exerts more profound hypoxic effect on the remant liver than on the normal one.

Sequential decrease in platelet energy charge after hepatic resection in cirrhotics

The adenylate energy charge of human platelets was measured in the early postoperative period after hepatic resection in cirrhotic and noncirrhotic patients to evaluate the metabolic status of platelets in this period. The adenylate energy charge of platelets decreased on the first, second, and third postoperative days in the cirrhotic group, whereas no significant decrease was found in the noncirrhotic group. A decrease in the percentage of adenosine triphosphate and an increase in that of hypoxanthine also occurred concomitant with a decrease in the adenylate energy charge, which was considered to be the result of an increased utilization of adenosine triphosphate. These findings indicate that in cirrhotic patients, the intravascular activation of platelets takes place and platelet function is damaged during the period immediately after hepatic resection, even when there is no clinical evidence of intravascular coagulation.

Adenine nucleotide metabolism of blood platelets in human liver cirrhosis.

The adenylate energy charge of human platelets was measured in normal subjects and cirrhotic patients using a method by labelling the adenine nucleotide pool of platelets with radioactive adenine. Using the above method, it was demonstrated that a reliable value for the adenylate energy charge can be obtained from platelet rich plasma containing more than 10(4) platelets per microliter after 30 minutes incubation. A significant difference was found in the distribution of adenine nucleotide metabolites between normal subjects and cirrhotic patients. However, no significant difference was found in the adenylate energy charge between two groups. These results indicate that energy metabolism of platelets is impaired to some extent in liver cirrhosis.

Acute Responses of Blood Ketone Body Ratio following Devascularization and Revascularization of Rabbit Liver

Acute changes associated with anhepatic and revascularized state were analyzed in relation to mitochondrial energy metabolism in rabbits. Fifteen minutes after the induction of anhepatic state, the ketone body ratio in the arterial blood decreased markedly from 0.833 to 0.229. The ketone body concentration also decreased to 24% of the normal value. The blood ketone body ratio and concentration remained low during the next 45 min. Pyruvate and lactate levels and the pyruvate/lactate ratio in the arterial blood changed very little during the 60-min anhepatic state. In a revascularization model following a 15-min anhepatic state, the ketone body concentration rose rapidly and then declined gradually, finally attaining a constant level at 30 min. The decreased blood ketone body ratio recovered to 0.55 at 30 min, and achieved steady state thereafter. Mitochondrial phosphorylative activity and hepatic energy charge showed almost normal levels 60 min after revascularization following the 15-min anhepatic state. These results indicate that the rapid metabolic alterations associated with the anhepatic and revascularized state can be accurately determined by measuring the arterial blood ketone body ratio, and they suggest that the ketone body ratio may serve as a convenient parameter for the evaluation of liver viability in pathological states such as operative ischemia or liver transplantation.