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Biomedical subjects

Y Shimahara

Publications and source records attributed to Y Shimahara.

At least 91 records · Page 5Linked to original sources

Arterial ketone body ratio as a possible indicator for liver transplantation in fulminant hepatic failure.

Arterial ketone body ratio (AKBR [acetoacetate/beta-hydroxybutyrate]) was measured in nineteen patients under medical supportive therapy for fulminant hepatic failure (FHF), in order to evaluate its predictive value relative to liver transplantation. Of the 19 patients 8 (42%) were salvaged and 11 (58%) died. Seven of 8 survivors showed an increased AKBR over 0.6 at 24-hr after admission, and all of them showed AKBR over 0.8 at 48-hr with subsequent maintenance of the value over 1.0. By contrast, all 11 nonsurvivors demonstrated sustained suppression of AKBR below 0.4 from 24 to 72 hr after admission. AKBR values at 24 and 48 hr showed statistically significant differences between survivors and nonsurvivors. Neither the grade of portal systemic encephalopathy (PSE) nor other conventional laboratory parameters--such as AST, bilirubin, ammonia, prothrombin time, hepaplastin test, fibrinogen, and platelet count--could discriminate between survivors and nonsurvivors by univariate analysis. These results indicate that AKBR can accurately predict the prognosis of FHF at the initial 24-48 hr after admission, and that it can play an important role in setting the indication of FHF for liver transplantation.

Adult↗

Energy metabolism of porcine liver during a 72-hour hypothermic perfusion with UW solution.

Porcine livers were preserved for 72 h using continuous hypothermic perfusion with UW solution and fluorocarbon emulsion (FC-43). They were then recirculated with human blood for 2 h at 37 degrees C for the evaluation of their viability. During hypothermic perfusion and recirculation, the main metabolites of the perfusate and adenine nucleotide concentrations were measured in order to examine the energy metabolism of the livers. This study revealed that hypothermically perfused livers, which mainly utilize endogenous fatty acids as an energy substrate during this time were adequately preserved for 72 h. In terms of energy metabolism, it is suggested that when using the method of continuous hypothermic perfusion with UW solution and FC-43, the administration of adequate amounts of certain fatty acids might prolong the preservation period.

Adenine Nucleotides↗

[Extensive liver resection according to redox theory].

Postoperative mortality and morbidity are determined by intraoperative stress calculated by changes in arterial ketone body ratio (AKBR) during hepatectomy. In this report, we introduced two types of operative procedure which aims not to decrease AKBR during operation. One is total vascular exclusion (HVE) for liver resection using venovenous bypass which improved the deleterious effects of portal pooling and decreased return of blood to heart. The other is the hepatic resection applying the technique used in the transplantation from the living related donor. In this procedure, the remnant liver works for decreasing the intraoperative stress. The tumor involving lobe is removed under cold perfusion and the tumor is removed on the back table. Then, the tumor free liver is transplanted to the same position.

Carcinoma, Hepatocellular↗

Diurnal fluctuations of arterial ketone body ratio in normal subjects and patients with liver dysfunction.

To explore the metabolic aspects of chronic liver disease, diurnal changes of arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox potential, were investigated in normal subjects, patients with chronic liver disease (Child's class A or B), and patients with hepatic failure (Child's class C). Ketone body ratio in normal subjects increased after breakfast from 0.96 to 2.00, after lunch from 2.17 to 2.38, and after dinner from 1.23 to 2.55 with blood glucose level ranging from 103 to 141 mg/dL (5.7 to 7.8 mmol/L). By contrast, the ketone body ratio in the Child A or B group changed little and remained within a range of 0.70-1.35 despite a large change in blood glucose level from 102 to 176 mg/dL (5.7 to 9.8 mmol/L). Ketone body ratio in Child's class C remained near or below 0.4 with no response to glucose administration, despite a marked elevation in blood glucose level. These results indicate that hepatic mitochondrial redox potential undergoes diurnal changes in sharp response to meals in normal liver function but that these fluctuations are absent in patients with liver damage (Child's class A, B, and C). Furthermore, it remains at low levels in severe liver failure (Child's class C). It is also suggested that hepatic mitochondrial redox potential plays an important role in the regulation of blood glucose levels.

Acetoacetates↗

Hepatomuscular failure in septic catabolism: altered muscular response to plasma proteolytic factor in decreased hepatic mitochondrial redox potential.

To estimate the contribution of muscle protein in whole-body protein catabolism, the muscular contribution index (MCI; urine 3-methylhistidine/urine total nitrogen) was determined in 49 cases of elective laparotomy, together with the arterial blood ketone body ratio (KBR; acetoacetate/beta-hydroxybutyrate), which reflects hepatic mitochondrial redox potential. MCI increased after operation and the occurrence of severe infection, provided KBR was maintained above 0.7. In patients with sepsis, however, MCI decreased dependently with KBR (n = 33; p less than 0.01). In these patients, plasma proteolysis-inducing activity determined by in vitro bioassay increased in inverse proportion to KBR (n = 20, p less than 0.01). Moreover, plasma concentrations of not only aromatic but also branched-chain amino acids markedly increased when KBR decreased to below 0.4 (n = 23; p less than 0.05). Thus the role of muscle protein in septic catabolism is diminished under reduced hepatic mitochondrial redox potential, despite the rapid increase of proteolysis-inducing activity. This finally leads to the failure of amino acid uptake by muscles, as well as liver. These results suggest that the deteriorated substrate exchange may form the metabolic background for multiple systems organ failure, which is often preceded by reduced KBR.

Biomarkers↗

The outcomes of the operated hepatocellular carcinoma patients.

During the past 5 1/3 years, we have performed 521 hepatic resections, of which 308 cases were hepatocellular carcinomas (HCC). Two hundreds and sixty cases of the 308 HCC patients were studied on their outcomes. These patients included 198 males and 62 females, whose ages ranged from 29 to 84 years. Underlying cirrhosis of the liver was found in 66% of the patients. Hepatectomized patients were classified into 5 groups according to the curability as follows; Group A, the resection of the tumor-bearing segment and additional segment; Group B, the complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, the complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, the incomplete resection of the tumor; Group E, the surgical approach for advanced HCC with tumor thrombi in the main trunk or the 1st branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D and E was 14 (5.4%), 105 (40.4%), 61 (23.4%), 14 (5.4%) and 66 (25.4%), respectively. There were 5 death (2.6%) among the 194 patients of Group A-D within 30 days after operation and 12 death (18.2%) in Group E. The overall 5-year survival rate of all 249 patients except for 11 surgical death cases was 32%. Whereas, 5-year survival rate for Group A and B were 100% and 47%, 4-year rate for Group C was 44%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The experimental study on the temporary portal vein arterialization in the canine liver transplantation: preliminary report.

To evaluate the feasibility of temporary portal vein arterialization (PVA) in orthotopic partial liver transplantation (PLT), we performed 5 canine PLTs with PVA assessing the changes in arterial ketone body ratio (AKBR) as an index of hepatic energy status, and measuring portal pressure and flow. After anastomosis of hepatic vein, the graft liver was revascularized with arterial blood shunted from the external iliac artery to the hepatic side of the portal vein. By using this technique, both anhepatic period of the recipient and ischemic time, especially warm ischemic time, of the allograft were markedly shortened (31.0 +/- 4.5 min: Mean +/- SEM). Four out of 5 recipients survived for at least 5 days (13 days in average). The AKBR was restored immediately after PVA and showed almost the same values as those at preclamping and after completion of anastomoses of both portal vein and hepatic artery. No significant difference in portal venous pressure was observed between during PVA and after vascular reconstruction. Portal blood flow during PVA was about one fourth of the total hepatic blood flow at preclamping. These results suggest that PVA can be used as an alternative procedure in PLT.

Anastomosis, Surgical↗

[Clinical investigation of hepatectomies for hepatocellular carcinoma--significance of extended hepatectomy for advanced hepatocellular carcinoma].

Although the diagnostic methods for hepatocellular carcinoma (HCC) are now being improved, there are still many cases detected at advanced stage. We, based on the Redox theory and using a technique of vascular surgery and liver transplantation, made it possible to perform the extended hepatectomy more actively even in the advanced cases which were previously considered to be in-operable. We report these extended hepatectomies in this paper. From January 1985 to August 1989, we performed 263 hepatectomies for HCC. Out of these 263 cases, we examined 208 cases which had an interval more than three months from the time of the operation and had exact follow-up data at the end of August 1989. There are 57 extended hepatectomies and they consist of 4 groups as follows. 1) Multiple group (14 cases): the operation for the cases with multiple daughter nodules in both lobes besides the main tumor. 2) Thrombus group (30 cases): the operation for the cases with portal tumor thrombus in the first branch or the main trunk of portal vein. 3) IVC group (4 cases): the operation adding resection and reconstruction of IVC because tumor was hardly fixed to the wall of IVC. 4) Recurrence group (9 cases): the operation for hepatic recurrence. Six cases of the Multiple group survived more than one year and one case is still alive more than two years after surgery. The 6-months, 1-year and 2-year cumulative survival rates of the Multiple group are 50.5%, 38.3%, and 8.5% respectively and these results are better than other reports. Forty-three hepatic recurrences were observed in 138 cases whose tumor was completely resected macroscopically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changes in arterial ketone body ratio in the phase immediately after hepatectomy. Prognostic implications.

Postoperative fluctuations of the ketone body ratio in arterial blood (acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox potential, were analyzed in 266 hepatectomized patients in relation to their prognosis. Changes in ketone body ratio were classified into the following two types: a primary decrease at the end of operation and a secondary decrease after transient recovery. Patients were classified into three groups by the primary decrease of ketone body ratio: group 1 (183 cases) with ketone body ratio above 0.7, group 2 (49 cases) between 0.7 and 0.4, and group 3 (34 cases) below 0.4 Ketone body ratio was restored to above 0.7 in 2.5 +/- 0.2 days (mean +/- SE) in all group 2 patients. However, though it was restored within 4.5 +/- 0.4 days in 26 group 3 patients, the other 8 died of multiple organ system failure in 7.4 +/- 2.8 days without recovery of ketone body ratio. This was followed by a secondary decrease in ketone body ratio to below 0.7 in 94 patients, concomitant with complications. The degree of the secondary decrease was positively correlated with that of the primary decrease. In the secondary decrease, of 42 patients with ketone body ratio below 0.4, 28 died of multiple organ failure. Total mortality was 7% in group 1, 12% in group 2, and 50% in group 3. It is suggested that the primary decrease in ketone body ratio at the end of operation is a decisive factor in the prognosis for hepatectomized patients.

Adult↗

Truncoumbilical bypass of the portal vein in radical resection of biliary tract tumour involving the hepatic duct confluence.

Before combined resection of the right hepatic lobe and the hepatoduodenal ligament, an autogenous external iliac vein was interposed between the root of the portal vein trunk and the umbilical portion of the vein in four patients with biliary tract tumour. The left hepatic arterial pathway was preserved, except in one case in whom resection of this artery was followed by reconstruction. This procedure allowed successful and safe extended right hepatic lobe resection and combined en bloc resection of the hepatoduodenal ligament while preserving hepatic blood perfusion.

Adenoma, Bile Duct↗

Impaired polymorphonuclear leucocyte function in patients undergoing hepatectomy: adenylate energy charge and superoxide anion production in relation to hepatic mitochondrial redox state.

Patients undergoing hepatectomy have an increased susceptibility to infection. We therefore studied the energy metabolism of the polymorphonuclear leucocyte (PMN), focusing on energy charge and function, especially superoxide anion (O2-) generation, in relation to the hepatic mitochondrial redox state. By labelling the PMN adenine nucleotide pool with radioactive adenine and by superoxide dismutase-inhibitable reduction of ferricytochrome c, the energy charge and O2- production was measured in 18 patients with hepatoma (non-cirrhotic, seven; cirrhotic, 11) undergoing hepatectomy. Their arterial ketone body ratios (KBRs), reflecting the hepatic mitochondrial redox potential, were above 0.7 before operation. After surgery, the 18 patients were divided into two groups: group A, KBR greater than 0.7, n = 10; and group B, KBR less than 0.7, n = 8. The energy charge and O2- release in group B decreased significantly from preoperative values (P less than 0.001 and P less than 0.01 respectively) and when compared with group A (P less than 0.05 and P less than 0.01 respectively). These results suggest that impaired hepatic energy metabolism (KBR less than 0.7) in hepatectomized patients leads to impaired energy charge and O2- production in the PMNs.

Adenine Nucleotides↗

Evaluation of temporary portal vein arterialization: the minimum arterialized blood flow for maintaining liver viability.

The effect of temporary portal vein arterialization (PVA) on hepatic energy metabolism was investigated by changes in the arterial blood ketone body ratio (KBR) and hepatic energy charge (EC) level in 17 dogs. The KBR decreased markedly after clamping the hepatic hilar vessels combining mesocaval shunt and remained at a low level throughout hepatic ischemia. After PVA, the KBR was rapidly restored and maintained at sufficient levels. EC at 60 min after arterialization also recovered to the preclamping level. By reducing the arterial shunt flow, the critical point of arterialized blood flow for maintaining the KBR at high levels was assessed to be about 10% of the total hepatic blood flow (THBF). These findings demonstrate that temporary PVA is an effective method for maintaining the functional capacity of the liver, and that the minimum arterialized blood flow needed to preserve liver viability is only about 10% of the total hepatic blood flow.

3-Hydroxybutyric Acid↗

Influence of colloidal carbon phagocytosis as a metabolic load on the hepatic energy metabolism in rats.

The influence of phagocytosis on hepatic energy metabolism was investigated in rats injected with colloidal carbon. Following injection of 6 mg colloidal carbon per 100 g body wt (BW) the hepatic energy charge potential (ECP) remained unchanged. However, oxidative phosphorylation of the isolated mitochondria (PR) increased significantly to 120 and 124% of the control at 1 and 3 hr, respectively, and returned to the normal range at 6 hr. The pyruvate level rose to 195 and 150% at 3 and 6 hr. The lactate level was elevated to 195 and 143% at 3 and 6 hr. Following injection of 20 mg colloidal carbon per 100 g BW, the ECP decreased from 0.865 to 0.783 at 1 hr, but recovered to the normal range thereafter. The PR increased more markedly to 135% at 1 hr, concomitant with an elevation of the ketone body ratio. At 3 hr it remained elevated at 118%, but returned to the normal level at 6 hr. The pyruvate and lactate levels increased to more than 250% at 1 and 3 hr. At 6 hr, the lactate level returned to the control level, but the pyruvate level showed still higher level than the control. These results indicate that phagocytosis exerts an acute metabolic load on the total liver. It was tentatively proposed that parenchymal and nonparenchymal cells in the liver have interrelation in the energy metabolism, and that an enhancement of hepatocellular mitochondrial phosphorylative activity occurs to assist the accelerated metabolism due to phagocytosis.

Adenine Nucleotides↗

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.

Carcinoma, Hepatocellular↗

Hepatic resection for advanced hepatocellular carcinoma with removal of portal vein tumor thrombi.

In 13 of 398 patients who underwent hepatectomy, tumor thrombi of the remnant portal vein was concomitantly removed by the balloon catheter method in 8, an open method under hepatic vascular exclusion in 1, and resection of the occlusive portal segment followed by portal reconstruction in 4. In 8 of these patients the liver was cirrhotic. The mode of hepatectomy consisted of bisegmetectomy or trisegmentectomy in 11, segmentectomy in one, and partial resection in one patient. Two patients died of portal thrombosis or hepatic failure in the hospital. The mean survival in four patients was 12 months. Seven are still alive (mean, 16 months). In the corresponding period, nine patients with occlusive tumor thrombi of the portal confluence were hospitalized without operation and survived up to 4 months (mean, 64 days) after detection of the tumoral occlusion. The causes of death of the nine patients were bleeding esophageal varices, rupture of the tumor, or hepatic failure. It was revealed that removal of tumor thrombi in the remnant portal vein contributes to (1) portal decompression, (2) feasibility of arterial embolization, and (3) increase in resectability of the main tumor. At present, this procedure might be regarded as an emergency procedure for the avoidance of the above lethal impendence, but it may open the door to an adjuvant therapy.

Aged↗

Influence of dopamine on the liver assessed by changes in arterial ketone body ratio in brain-dead dogs.

The influence of dopamine on liver metabolism in the state of brain death was assessed by measuring arterial ketone body ratio (AKBR) in dogs. Mean arterial blood pressure (MABP) was significantly decreased, from 137.4 +/- 3.7 to 64.7 +/- 2.8 mm Hg, 1 hour after completion of brain death (p less than 0.01). In the control group AKBR was maintained at the near control value of 1.07 thereafter, concomitant with a significant decrease in serum lactate levels, despite marked hypotension (p less than 0.05). Dopamine infusion at rates of 5 and 10 micrograms/kg/min sustained both AKBR and MABP at near control values. In contrast, dopamine given at doses greater than 15 micrograms/kg/min caused a significant reduction of AKBR, to less than 0.66 +/- 0.12 (p less than 0.01), although MABP was restored to near-normal levels. In addition, serum levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase were significantly elevated, reflecting liver cell injury. It is suggested that the liver is primarily tolerant to hypotension in the state of brain death and that dopamine administered at a rate of 15 micrograms/kg/min or more impairs liver metabolism by reducing the redox state (free nicotinamide-adenine dinucleotide/reduced nicotinamide-adenine dinucleotide) of liver mitochondria.

Animals↗

Prognostic implications of postoperative suppression of arterial ketone body ratio: time factor involved in the suppression of hepatic mitochondrial oxidation-reduction state.

To determine the tolerance limit of the liver in the critically suppressed mitochondrial oxidation-reduction state, the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate), which reflects hepatic mitochondrial oxidation-reduction potential, was measured 1319 times in 161 patients during the postoperative critical period. Because patients who showed arterial ketone body ratios between 0.40 and 0.25 had a higher incidence of postoperative complications than had those who showed ratios above 0.40, this was designated as the critical zone of the arterial ketone body ratio. When duration in the critical zone was less than 2 days, 90% of the patients were able to tolerate the condition and survive. By contrast, when an arterial ketone body ratio below 0.40 was prolonged for more than 5 days, there was a high incidence of multiple organ failure and a 100% mortality rate, with the average survival period after a 5-day suppression being estimated as 5.7 +/- 2.4 days. It is suggested that the arterial ketone body ratio in the critical zone must be returned to normal values within 2 days to obtain a good prognosis.

Adolescent↗