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Y Shimahara

Publications and source records attributed to Y Shimahara.

At least 127 records · Page 7Linked to original sources
PubMed1986

Evaluation of a short-time, oxygen carrier-free perfusion model in rat liver: mitochondrial energy metabolism and insulin effect.

Livers of rats fasted for 18 hr were perfused for 60 min at 37, 35, and 32 degrees C in a simple noncirculating system with a carbogen (95%, 5% CO2) equilibrated, oxygen carrier-free, glucose-containing (200 mg X dl-1) cristalloid perfusate (pH 7.4, 280 mosmol X kg-1) without or with the addition of insulin (10 U X hr-1), and analyzed for tissue ATP, ADP, AMP, acetoacetate, and beta-hydroxybutyrate as well as for parameters of the energy metabolism of isolated mitochondria. Perfusion without insulin at 37 degrees C caused significant alterations: ATP and total adenine nucleotides (TAN) dropped to 62 and 74% of the control values (3.33 and 4.57 mumol X g-1), respectively. The energy charge potential ECP decreased from 0.842 to 0.713. Also, the mitochondrial phosphorylation rate (PR), the respiratory control ratio (RC), and the state 3 respiration rate (ST 3) were significantly depressed to 62, 54, and 72% of the control values. Perfusion with insulin maintained a normal metabolic pattern: ATP 105%, TAN 97%, ECP 0.877, PR 94%, RC 69%, and ST 3 105%. The metabolic deterioration during insulin-free perfusion was decreased at 35/32 degrees C: ATP 67/82%, PR 72/95%, RC 74/87%. At 35 degrees C, insulin ameliorated the metabolic pattern, but normal ranges were no longer reached. At 32 degrees C, insulin had no effect.

3-Hydroxybutyric Acid↗
PubMed1985

Derangement of hepatic energy metabolism in lead-sensitized endotoxicosis.

Lead-sensitized endotoxicosis was investigated in rats in terms of hepatic energy metabolism. Lead acetate (Ld, 20 mg/kg BW) or endotoxin (Etx, 4 mg/kg BW) caused no deaths within 48 h. Ld plus Etx resulted in a lethality of 50 and 100% within 6 and 12 h respectively. Etx or Ld alone caused a slight but significant decrease in the hepatic tissue levels of total adenine nucleotides and/or ATP at 3 and 6 h after the application. The energy charge potential (ECP) remained normal. The ketone bodies acetoacetate and beta-hydroxybutyrate and the ratio AcAc/beta-OHB as well as the mitochondrial oxidative phosphorylation tended to increase; the hepatic tissue levels of pyruvate and lactate were increased after 3 h, indicative of an accelerated glycolysis. These alterations were no longer detectable after 6 h. In lead-sensitized endotoxemia (Ld + Etx), the total adenine nucleotides and ATP of the liver tissue decreased significantly to 84% (86%) and 71% (52%) of the controls within 3 and 6 h respectively, and the ECP had decreased from 0.865 to 0.684 at 6 h. The ketone bodies were increased, while the ratio AcAc/beta-OHB was significantly decreased at 6 h. The hepatic tissue lactate remained elevated. The mitochondrial activity was significantly reduced. A hyperglycemia (175 mg . dl-1) at 3 h changed into a hypoglycemia (50 mg . dl-1) at 6 h. It is suggested that Ld plus Etx causes a rapid impairment of hepatic mitochondria which leads to a drastic disturbance of the hepatic energy metabolism including hypoglycemia and contributes to an enhanced lethality in Ld-sensitized endotoxicosis.

Adenine Nucleotides↗
PubMed1984

Relationship of deranged energy metabolism in liver and kidney to arterial ketone body ratio following liver ischemia in rats.

Changes in energy metabolism in the liver and kidney in liver ischemia induced in rats were simultaneously studied, in terms of energy charge (EC) and mitochondrial oxidoreduction state. Mean arterial blood pressure, glucose and lactate, total ketone bodies (acetoacetate + beta-hydroxybutyrate) and the ketone body ratio in arterial blood (KBR) were also investigated. During and after liver ischemia, both organs showed similar patterns of reversibility, and KBR, which reflects the mitochondrial oxidoreduction state, correlated well with EC, in both organs. Referring to the mortality and changes in substrates above mentioned, KBR is a pertinent parameter for detection of viability following induced liver ischemia. It was also suggested that KBR may indicate a regulating role by the liver, in kidney energy metabolism.

Adenine Nucleotides↗
PubMed1983

Metabolic abnormalities associated with postoperative organ failure. A redox theory.

We studied metabolic abnormalities of postoperative organ failure in 55 patients and classified them into four groups according to the postoperative changes in the arterial blood-ketone body ratio (acetoacetic acid-beta-hydroxybutyric acid) reflecting hepatic mitochondrial redox potential: patients in group A had no decrease below 0.7, patients in group B had a transient decrease to 0.4, patients in group C had a progressive decrease to below 0.4, and patients in group D (terminal stage) had a decrease to below 0.25. All group A and B patients tolerated their operations well; the group C and D patients had multiple organ failure. In groups B, C, and D, plasma concentrations of alanine, proline, phenylalanine, and tyrosine were negatively correlated with the blood--ketone body ratio and the molar ratios between the plasma concentrations of branched-chain amino acids and aromatic amino acids were positively correlated with the blood--ketone body ratio. Hepatic energy deficit associated with decreasing blood-ketone body ratio may be the metabolic basis of postoperative organ failure.

3-Hydroxybutyric Acid↗
PubMed1982

Clinical experience of postoperative hepatic failure treatment with pig or baboon liver cross-hemodialysis with an interposed membrane.

The present study emphasizes the principle of using liver support to restore the blood ketone body ratio (acetoacetate/beta-hydroxybutyrate), which reflects the redox potential of liver mitochondria and correlates with hepatic energy charge (ATP + 0.5ADP/ATP + ADP + AMP). Eleven surgical patients with grade IV hepatic coma were treated by an ex vivo pig or baboon liver cross-hemodialysis with an interposed Cuprophan membrane when their blood ketone body ratios had decreased to below 0.4 compared with the normal of above 0.7. Three patients were treated by cross-hemodialysis using a standard Cuprophan membrane dialyzer without increase of blood ketone body ratio and without marked beneficial effect. However, five of eight patients who had blood ketone body ratios of above 0.25 became fully alert after treatment by cross-hemodialysis using the larger pore size and greater surface area Cuprophan membrane, concurrent with a rise in the decreased blood ketone body ratio, and three of them were later discharged. By contrast, in the three patients with blood ketone body ratios below 0.25, there was no restoration of consciousness and no improvement in their blood ketone body ratios by this liver support. It is suggested that, as long as the blood ketone body ratio remained over 0.25, this metabolic liver support is effective in restoring grade IV hepatic coma.

Aged↗
PubMed1982

The effects of heterologous liver cross-hemodialysis on adenylate energy charge of the remnant liver after major hepatic resection.

The effect of liver support on the adenylate energy charge (ATP + 0.5ADP)/(ATP + ADP + AMP) of the remnant liver after major hepatic resection was studied in rabbits. The present study emphasized the principle of restoring the decreased energy charge level of the remnant liver after major hepatic resection by use of an ex vivo heterologous liver cross-hemodialysis with an interposed Cuprophan membrane. The energy charge level provides the cell with a very sensitive intracellular control mechanism. Regulatory enzymes from biosynthetic sequences exhibit very little activity at low levels of energy charge, and their activities increase sharply at high-energy charge levels. The energy charge level of the remnant liver maximally decreased from the control level of 0.860 to 0.767 at 24 hours after 70% hepatectomy. The energy charge level increased from 0.767 to 0.857 after two hours of cross-hemodialysis with an interposed Cuprophan membrane between the 24-hour, 70% hepatectomized rabbit and an ex vivo pig liver with high energy charge. The above results suggest that this ex vivo pig cross-hemodialysis may be effective for biosynthesis in the regenerative processes of the remnant liver.

Adenosine Monophosphate↗
PubMed1982

The pathophysiology of septic shock: acute renal failure in rats following live E coli injection. A histochemical study of the proximal tubules.

Acute renal failure was induced in rats by injection of a lethal dose of live Escherichia coli. Enzyme activities of the proximal tubule were studied histochemically at three, six, and 12 hours following E coli injection. The enzymes examined were alkaline phosphatase (A1Pase), acid phosphatase (AcPase), adenosine triphosphatase (ATPase), succinate dehydrogenase (SDH), glucose-6-phosphatase (G6Pase), and glucose-6-phosphate dehydrogenase (G6PDH). At three hours, ATPase activity was slightly decreased, while other enzymes showed no changes in activities at this time. At six hours, a slight increase in AcPase activity was seen in the pars recta. At this time, although A1Pase showed no change in activity, other enzymes revealed slight decreases in activities: G6Pase and SDH in the pars convoluta, ATPase in the pars convoluta and pars recta, and G6PDH in pars recta. At 12 hours after treatment, all enzymes showed decreases in activities; however, no necrotic tubule changes were detectable by light microscopy. Since sodium reabsorption in proximal tubules requires a sodium pump consisting of Na-K ATPase, early histochemical changes in ATPase activity in proximal tubule following bacteremia may be related to early changes in sodium reabsorption causing polyuria and to the subsequent development of acute renal failure.

Acute Kidney Injury↗
PubMed1982

A study of oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following living Escherichia coli injection.

Mechanisms of subcellular dysfunction of the liver in sepsis are still obscure. The present study investigates changes in oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following live Escherichia coli injection (E coli, Serotype: 0--18. A 1.25--1.5 X 10(9)/100 gm body wt inoculum of E coli bacteria was injected via the tail vein, causing a 100% mortality rate within 24 hours after injection. In order to determine alteration of liver mitochondrial membrane permeability, serum ornithine carbamoyltransferase activity was measured following E coli injection. This activity increased ten to 100-fold over that of controls with time following injection. However, the yield of liver mitochondria from treated rats, estimated by the amount of collected mitochondrial protein and the recovery rate of succinate dehydrogenase activity in the final mitochondrial suspensions, was not significantly different from that of controls. Mitochondrial oxidative phosphorylative activity measured using glutamate as a substrate was enhanced throughout all period to death (P less than 0.01 at three and six hours, P less than 0.05 in the fatal stage) and was associated with concomitant increases in respiratory control ratios. Similar results were obtained using beta-hydroxybutyrate as a substrate. This enhancement was accompanied by an increase in 2-4-dinitrophenol-stimulated ATPase activity (160% at three hours and 130% in the fatal stage). Calcium-induced stimulation of mitochondrial respiration as well as initial calcium uptake rate linked to respiration, using glutamate as a substrate, were higher in liver mitochondria from rats with E coli treatment than in those of controls throughout all periods (P less than 0.01 or less). These results suggest the coexistence of hyperfunctioning as well as deteriorated mitochondria following lethal treatment with E coli.

3-Hydroxybutyric Acid↗
PubMed1981

Changes in blood ketone body ratio: their significance after major hepatic resection.

Changes in the ratio of acetoacetate to 3-hydroxybutyrate (the ketone body ratio) in arterial blood were investigated after massive liver resection in patients and rabbits. In a patient who had had a successful hepatectomy, the blood ketone body ratio decreased rapidly after the operation and then returned to the preoperative level; whereas in a patient who had had an unsuccessful hepatectomy, the blood ketone body ratio did not decrease rapidly after the operation. In 70% hepatectomized rabbits, the blood ketone body ratio decreased maximally nine hours after hepatectomy and then returned gradually to a normal level. The blood ketone body ratio paralleled the hepatic energy charge after 70% hepatectomy in rabbits. The measurement of the blood ketone body ratio is very useful for evaluation of the energy status of the remnant liver.

Acetoacetates↗
PubMed1981

Four stages of mitochondrial deterioration in hemorrhagic shock.

It is of great importance to define the manner in which cells are damaged and how intracellular derangement becomes irreversible during shock. When supply of both oxygen and substrates to cells is limited during shock, cellular energy metabolism of vital organs is severely depressed. In this experiment, the relationship was clarified between the reversibility of shock and the cellular energy status, from the viewpoint of hepatic energy change, mitochondrial redox state, ATP synthesis of isolated mitochondria, and fragility of mitochondrial membrane in rat livers. The derangement of energy metabolism passed through a series of four stages during hemorrhagic shock. At Stage I (initial stage), the cellular energy level decreased greatly due to marked energy consumption, without any organic damages in the mitochondria. Stage II (cell distress stage) showed that cellular energy imbalance occurred due to the depressed mitochondrial activity in vivo, although it was reversible when the blood supply was restored. Stage III (transitional stage) was the phase at which mitochondrial fragility increased severely. At Stage IV (terminal stage), mitochondria were markedly damaged organically and cellular energy metabolism was not remedied by any intensive therapies, which inevitably meant the death of vital organs.

Adenosine Diphosphate↗
PubMed1981

Effects of hypothermia on energy metabolism of metabolically loaded liver.

The effects of hypothermia on adenine nucleotide level, mitochondrial metabolism and redox state of the remnant liver were studied in 25, 50, 70 and 93% hepatectomized rabbits. In 25% of the hepatectomized rabbits, energy charge levels and mitochondrial phosphorylative activities remained unchanged, while in 50 and 70% hepatectomized rabbits, the energy charge levels decreased maximally at 24 hours after hepatectomy with a concomitant rise of mitochondrial phosphorylative activity. In 93% hepatectomized rabbits, the energy charge levels decreased rapidly without enhancement in mitochondrial phosphorylative activity and these rabbits died within 12 hours after hepatectomy. Body cooling significantly increased the energy charge of the remnant liver with further enhancement in mitochondrial phosphorylative activity in 25, 50 and 70% hepatectomized rabbits, but did not increase the energy charge in 93% hepatectomized rabbits. On the other hand, during body rewarming, the energy charge levels of the remnant liver decreased. More than 60% of 70% hepatectomized rabbits died during body rewarming, while all of 50% or less hepatectomized rabbits remained alive. Thus, body cooling may provide remarkable protection for the remnant liver from an energy crisis under the condition that compensatory mitochondrial enhancements are present.

Adenine Nucleotides↗
PubMed1981

The effects of cross-circulation and charcoal hemoperfusion on adenylate energy charge of the remnant liver after major hepatic resection.

The effect of liver support on the adenylate energy charge (ATP + 1/2 ADP) / (ATP + ADP + AMP) of the remnant liver after major hepatic resection was studied in rabbits. The present study emphasizes the principle of the use of homologous or heterologous liver for preventing the decrease in the energy charge of the remnant liver after major hepatic resection. The energy charge level provides the cell with a very sensitive intracellular control mechanism. Regulatory enzymes from biosynthetic sequences exhibit very little activity at low levels of energy charge, and their activities increase sharply at high charge values. The energy charge level of the remnant liver maximally decreased from the normal level of 0.843 to 0.767 at 24 hours after 70% hepatectomy. The energy charge level increased from 0.767 to 0.828 after one hour of cross-circulation of systemic blood between the 24-hour, 70% hepatectomized rabbit and a normal rabbit. An increase from 0.767 to 0.801 also occurred after one hour of charcoal hemoperfusion. Although either means of liver support serves to restore energy charge levels, the above results suggest that cross-circulation may be more effective than charcoal hemoperfusion for biosynthesis in the regenerative processes of the remnant liver.

Adenosine Diphosphate↗
PubMedDate not supplied

Apparent normobasemia as a negative prognostic sign immediately after hepatectomy.

The acid-base balance from the postoperative day (POD) 1 to POD 3 after cirrhotic liver resection was investigated in relation to operative outcome by conducting a retrospective study on the changes in arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, and arterial blood gas analysis. Patients were grouped according to their outcome: hospital death (HD) and or good outcome, the latter group acting as controls (CTR). Metabolic alkalosis developed in a significant number of the CTR patients (p < 0.01), who had high AKBR values. By contrast, metabolic alkalosis did not develop in the HD group, with significantly lower AKBR (p < 0.001), and there was almost normobasemia. There were no significant differences in the need for mechanical respiratory assistance, the amounts of fresh frozen plasma administered, and renal function test results between the two groups on each of 3 postoperative days. These data indicated that the absence of metabolic alkalosis during the early postoperative days reflects disruption of energy metabolism in the remnant liver, and that the apparent normobasemia is a significant indicator of poor prognosis after cirrhotic liver resection.

Acid-Base Equilibrium↗
PubMedDate not supplied

Liver resection for hepatocellular carcinoma (HCC) with direct removal of tumor thrombi in the main portal vein.

Since the tumor thrombus in the main portal vein appears in the terminal stage of hepatocellular carcinoma (HCC), any attempt to remove it surgically is thought to be impractical as the malignancy itself cannot be entirely removed. During the past 5 years, we have performed tumor thrombectomy combined with hepatectomy in 29 of 298 patients with HCC. This combined therapy was initially decided upon as an emergency measure to prevent impending rupture of esophageal varices, rather than to improve patient survival. Since portal flow was obtained after removal of thrombi, this condition enabled transcatheter arterial embolization (TAE) and/or percutaneous ethanol injection therapy (PEIT). Although improved patient survival was not the primary goal of the emergency operation and there was an operative mortality of 11%, half of the other patients in the present series had unexpectedly high survival rates of 1 year (52.2%), 2 years (23.2%), and 3 years (11.6%), which were significantly higher than in patients not undergoing operation (n = 22).

Aged↗
PubMedDate not supplied

Significance of nucleosides and a nucleotide mixture infusion on hepatic energy metabolism of 70% hepatectomized rabbits in postoperative phase.

BACKGROUND: The influence of administration of a nucleoside-nucleotide mixture on hepatic energy metabolism was investigated in 70% hepatectomized rabbits from 48 to 72 hours after hepatectomy. METHODS: From 48 to 72 hours after hepatectomy, animals underwent continuous i.v. infusion of 2 mL/kg body weight/h of 9 g/L NaCl (group S), 5.99 mmol/L nucleoside-nucleotide mixture (group N1) or 11.98 mmol/L nucleoside-nucleotide mixture (group N2). RESULTS: At 72 hours, there was no significant difference in the hepatic adenylate energy charge among groups (S, 0.84 +/- 0.01; N1, 0.82 +/- 0.02; N2, 0.85 +/- 0.01). The hepatic mitochondrial phosphorylation rate was 66.9 +/- 2.5, 76.3 +/- 11.1, and 108.4 +/- 14.1 nmol ATP/mg mitochondrial protein/min in groups S, N1, and N2, respectively. The value of group N2 was significantly higher than the value of group S (p < .01). In addition, DNA concentration of the remnant liver was 2.27 +/- 0.07, 2.56 +/- 0.17, and 3.19 +/- 0.42 mg/g wet liver in groups S, N1, and N2, respectively, showing a significant increase in group N2 compared with group S (p < .05). CONCLUSION: A continuous i.v. infusion of a nucleoside-nucleotide mixture to 70% hepatectomized rabbits from 48 to 72 hours after hepatectomy prolonged an enhancement of the hepatic mitochondrial phosphorylation rate and elevated DNA content of the remnant liver.

Adenine Nucleotides↗