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Biomedical subjects

Y Kamiyama

Publications and source records attributed to Y Kamiyama.

At least 163 records · Page 9Linked to original sources

Pyridine nucleotide fluorometry in preserved porcine liver with fluorocarbon emulsion.

Oxidation-reduction changes in pyridine nucleotide fluorescence were investigated in perfused and preserved porcine liver. A fluorocarbon emulsion (FC-43) was administered to the perfusate as an oxygen carrier to obtain full oxidation level by portal perfusion at a physiological low flow rate. A satisfactory reading was obtained by portal perfusion with EuroCollins' solution containing 10% v/v FC-43 at a rate of 0.5 ml/min/g liver. The amplitude (R x A) and the changing velocity (R x V) from full oxidation to full reduction were determined in the resultant trace curve. Both R x A and R x V decreased in inverse proportion to the duration of preservation period (3, 6, 12 hr). Adenine nucleotide content, hepatic energy charge level, and ketone body ratio in the tissue were simultaneously measured, and they also decreased proportionally to the duration of preservation. There were close positive correlations between R x A and total adenine nucleotide concentration (r = 0.841, P less than 0.01), between R x V and energy charge (r = 0.787, P less than 0.01), and between R x V and tissue ketone body ratio (r = 0.881, P less than 0.01). These results suggest that pyridine nucleotide fluorometry can accurately follow the cellular function of isolated porcine liver by administration of FC-43 in perfusate. This fluorometry may also have potential application in evaluating viability of a large organ like the human liver graft.

Adenine Nucleotides↗

The effects of PGI2 analog (OP-41483) on perfused porcine liver.

The effects of a prostacyclin analog OP-41483 on energy metabolism were studied in an isolated porcine liver perfused with human blood for 8 h. OP-41483 was administered intravenously at a rate of 0.3 microgram/kg/min during the procurement and into the perfusate at a rate of 1.0 microgram/min during perfusion. Acetoacetate, beta-hydroxybutyrate, lactate, and pyruvate were measured before perfusion and at 1, 2, 3, 5, and 8 h after perfusion, from which values the ketone body ration (acetoacetate/beta-hydroxybutyrate, KBR), reflecting the redox state of liver mitochondria, was calculated. In the OP-41483 group, KBR increased rapidly from 0.34 to 0.95, 1.61, 1.51, 2.35, and 2.04, and lactate decreased rapidly from 9.81 to 6.30, 4.51, 3.22, 2.39, and 1.33 mmol/L at the respective hours after perfusion. There were significant differences after 3 h of perfusion as compared with the control group (p less than 0.05). These results suggest that administration of OP-41483 causes an increase in mitochondrial NAD+/NADH ratio (oxidized and reduced forms of free nicotinamide-adenine dinucleotides), leading to an enhancement of the metabolic capacity of the perfused liver.

3-Hydroxybutyric Acid↗

Effects of partial deprivation of portal blood on arterial blood ketone body ratio in rabbits.

To examine the effects of portal blood deprivation on energy metabolism of the liver, we studied: (1) the ketone body ratio (acetoacetate/beta-hydroxybutyrate) in liver tissue, which is in equilibrium with the free NAD+/NADH ratio in liver mitochondria, in the ligated lobe (LL) and nonligated lobe (NLL), (2) the hepatic energy charge [EC = (ATP + 1/2 ADP)/(ATP + ADP + AMP)] in both LL and NLL, and (3) the arterial blood ketone body ratio (BKBR) after left portal vein branch ligation (PBL) in rabbits. As found in LL after PBL, portal blood deprivation decreased the tissue ketone body ratio. The EC in LL significantly decreased after PBL, but recovered 7 days after PBL since the LL became atrophic. The BKBR remained within the normal range, even when 60% of the total liver was deprived of portal blood.

Animals↗

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.

Animals↗

Taurocholate-induced gastric damage in rats with obstructive jaundice.

We examined the severity of taurocholate-induced gastric mucosal damage in rats with obstructive jaundice. Oral administration of 100 mM taurocholate induced severer gastric mucosal damage in rats with jaundice than in intact rats. Pretreatment with 5 mM taurocholate significantly protected the gastric mucosa against 100 mM taurocholate-induced damage, suggesting adaptive cytoprotection in rats with jaundice. The reductions in the gastric mucosal potential difference and hexosamine contents in the gastric mucosa in response to 100 mM taurocholate were significantly attenuated by prior administration of 5 mM taurocholate in both intact rats and rats with jaundice.

Animals↗

[The effect of celiac plexus block on splanchnic circulation; changes in systemic hemodynamics and tissue blood flow of the liver and kidney in rabbits].

The effects of the celiac plexus block (CPB) on the hepatic and renal tissue blood flow (TBF) were investigated in 45 rabbits. Together with this, the effects of drugs (phenylephrine: PE, norepinephrine: NE, dopamine: DA, 6% hydroxyethyl starch: HES) used to increase mean blood pressure (MBP) up to control level were also investigated. TBF was measured by the hydrogen clearance method. Following CPB, MBP and heart rate decreased significantly. TBF of the liver and kidney both decreased significantly for 14.3% and 25.9% respectively. A correlation was observed between the decreases of MBP and renal TBF. An increase in hepatic TBF beyond the control level was observed in DA group, and in both hepatic and renal TBF in the HES group after adjustment of MBP. In other groups, both hepatic and renal TBF tended to decrease. It was concluded that hepatic and renal TBF decreased because of hemodynamic suppression following CPB. The results also suggest that both TBFs would have increased if systemic hemodynamic change was not so great.

Animals↗

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.

Aged↗

Effects of perfusion pressure during flushing on the viability of the procured liver using noninvasive fluorometry.

The influence of perfusion pressure and flow rate on hepatic cellular viability was investigated in the procured liver using noninvasive pyridine nucleotide fluorometry, in relation to other metabolic indices such as nicotinamide adenine dinucleotide (NAD) concentration, adenine nucleotides, tissue ketone bodies, and mitochondrial phosphorylative activity. Rat liver was perfused at a controlled flow rate through the portal vein with a nonrecirculating open-end-design perfusion system driven by a roller pump using cooled oxygenized Euro-Collins' solution. The maximum pressures (mean pressure in parentheses) of experimental groups were 8 (5) mmHg, 15 (9) mmHg, 40 (25) mmHg, 80 (50) mmHg, 120 (73) mmHg, 240 (152) mmHg. The amplitude between oxidation and reduction levels (RxA) in the fluorometric trace, and the gradient or velocity of the trace curve from oxidation to reduction (RxV) were determined by the measurement of fluorescence from NAD phosphate, reduced form (NADPH) using a new fluorometric device. Other metabolic indices were measured after attainment of a fully oxygenated state. RxA decreased in accordance with the increase of pressure. Similar results were obtained in the changes of NAD concentration, total adenine nucleotides, and total tissue ketone bodies, possibly due to the wash-out of these metabolites. RxV decreased in inverse proportion to the increase of pressure. There were close positive correlations between RxV and tissue ketone body ratio (acetoacetate/3-hydroxybutyrate) (r = 0.793, less than 0.01), RxV and respiratory control ratio in isolated mitochondria (r = 0.617, P less than 0.05), RxV and state 3 respiration (r = 0.792, P less than 0.01), and RxV and phosphorylation rate (r = 0.833, P less than 0.01). These results suggest that perfusion pressure and flow rate can easily deteriorate the energy metabolism of the procured liver, and that the gravity-induced hydrostatic pressure presently used in procurement perfusion should be reevaluated on the basis of energy metabolism.

Animals↗

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.

Adenosine Triphosphate↗

Effects of partial ischemia and reflow on mitochondrial metabolism in rat liver.

To clarify the effects of partial ischemia and reflow on the mitochondrial metabolism of the rat liver, the afferent vessels supplying the left lateral and left half of medial lobes were occluded and then reperfused after given time periods of ischemia (30, 60, 90 and 120 min, groups A, B, C and D, respectively). Samplings were taken at 0, 10 and 60 min after reperfusion. The energy charge levels of ischemic lobes decreased rapidly from 0.85 +/- 0.01 in the sham group to 0.38 +/- 0.11, 0.35 +/- 0.07 and 0.34 +/- 0.06 in groups B, C and D, respectively. The phosphorylative activities of mitochondria isolated from ischemic lobes decreased gradually along with the time of ischemia. The reversal of mitochondrial function and energy charge levels following reperfusion was noted in groups A and B. In nonischemic lobes, the phosphorylation rate (nmol ATP/mg/min) increased from 90 +/- 6 in sham group to 125 +/- 12 and 130 +/- 9; 131 +/- 5 and 130 +/- 6; 123 +/- 6 and 122 +/- 17, and 138 +/- 6 and 138 +/- 13 at 10 and 60 min after reflow in groups A, B, C and D, respectively (p less than 0.05). The energy charge level of nonischemic lobes decreased from 0.85 +/- 0.01 of sham group to 0.80 +/- 0.03 in group D (p less than 0.05). From these results, it is concluded that the transitional zone for the reversal of mitochondria function and energy metabolism following prolonged liver ischemia appears at around 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Peptic ulcer and gastric acid secretion in patients with insulinoma.

We evaluated the incidence of associated peptic ulcers and the gastric acid secretion in our 20 series of insulinoma, and obtained the following results: 1) Four out of 20 patients (20%) with insulinoma were associated with peptic ulcers. 2) Except for the maximum acid concentration, the preoperative gastric secretion tests, such as the basal acid output and maximum acid output, failed to indicate hyperacidity in those patients. And patients with a short duration of illness by insulinoma neither showed hyperacidity nor were associated with peptic ulcers. 3) A tendency of reduced gastric acid secretion and the amelioration of peptic ulcers was observed in those who underwent the extirpation of insulinoma. 4) In the most recent case received gastric analysis with continuous monitoring of blood glucose level, an increase of basal acid output was observed during the hypoglycemic period in which the blood glucose levels reduced to around 30 mg/100 ml. These results indicate that the low blood glucose level and the high gastric acid secretion produced under the condition on an empty stomach, may be important factors related to the high association rates of the peptic ulcers in patients with insulinoma.

Adenoma, Islet Cell↗

[Pathophysiology following biliary reconstruction procedures, with special reference to gastric acid secretion, peptic ulcer, metabolism of carbohydrate and fat, and gastrointestinal hormone release].

Pathophysiological effects following biliary tract reconstruction for benign biliary diseases were investigated from the standpoint of gastric acid secretion, metabolism of nutrients and gastrointestinal hormone release. Patients undergoing Roux-Y hepaticojejunostomy showed a significant increase in maximum acid output at follow-up, although only one case of peptic ulcer was observed. In addition, the frequency of cases showing gastric acid hypersecretion was higher than for jejunal interposition hepaticoduodenostomy. Two kinds of test meals (carbohydrate-rich or fat-rich) were given, on different days, to each patient before and about four weeks after surgery. Plasma concentrations of gastrointestinal hormones and glucose or triglyceride were determined. Fasting concentrations of gut hormones (gastrin, GIP, insulin and GLI) were similar to those before surgery, and increased after the ingestion of the test meals. Gastrin and total GLI levels tended to be higher in the Roux-Y than in the interposition group, and vice versa for both insulin and GIP. The changes in plasma glucose and triglyceride, following the Roux-Y procedure, suggest disturbances in carbohydrate tolerance, fat digestion, and in the anabolic phase of absorbed fat. Patients undergoing the Roux-Y procedure should be carefully followed up, since gastric acid hypersecretion induced by a postprandial augmented release of gastrin was observed.

Adult↗

Deleterious effects of splanchnic congestion on hepatic energy metabolism following repeated portal triad cross-clamping in dogs.

Thirty minutes of warm hepatic ischemia produced by portal triad cross-clamping was repeated five times at 30-minute intervals in three groups of five dogs each: Group A was subjected only to portal triad cross-clamping; Group B received simultaneous clamping of the celiac axis and the superior mesenteric artery; and Group C had a simultaneous splenojugular shunt. The arterial blood ketone body ratio (acetoacetate/beta-hydroxybutyrate: KBR), reflecting the NAD+/NADH ratio in liver mitochondria, decreased significantly after each cross-clamping in all groups. After the first declamping, there was no significant difference in the recovery rate of the KBR among the three groups. After the second declamping, the recovery rate in Group A decreased significantly compared with the rates of Groups B and C (P less than 0.05). After the fourth declamping, the recovery rate in Group B was significantly lower than that of Group C (P less than 0.05). The hepatic energy charge [(ATP + 1/2ADP)/(ATP + ADP + AMP)] 30 minutes after the fifth declamping decreased significantly to 0.75 +/- 0.01 in Group A, compared with 0.84 +/- 0.01 in Group C (P less than 0.01). The lactate and total free plasma amino acid levels in the arterial blood increased significantly in the order of Groups A, B, and C. It is suggested that the inflow of stagnant portal venous blood to ischemic liver impairs hepatic energy metabolism.

Amino Acids↗

Amelioration of normothermic canine liver ischemia with prostacyclin.

A model of hepatic ischemia was developed in dogs using a pump-driven splanchnic-to-jugular vein bypass during crossclamping of the portal triad. An LD50 was established with three hours of ischemia. PGI2 given for one hour before the ischemic insult ameliorated the ischemic injury and increased survival.

Animals↗

Evaluation of cytoprotective drugs for liver preservation by pyridine nucleotide fluorometry.

The cytoprotective effects of membrane-stabilizing drugs, such as chlorpromazine, allopurinol, dibucaine, phenoxybenzamine, and OP41483 (prostacyclin analogue), administered to perfusate and preservation medium were studied in rat liver, after 24 hours' preservation, by assessment of pyridine nucleotide fluorescence. On the fluorometric trace curve, amplitude (RxA) and velocity (RxV) from oxidation to reduction were determined. Percent decrease of RxA (%RxA) and that of RxV (%RxV) after 24 hours' preservation were calculated. At the end of preservation, the concentration of total adenine nucleotides of the liver, hepatic adenylate energy charge, and prepared mitochondrial oxidative phosphorylative activity were also measured. In the groups given phenoxybenzamine, dibucaine, and allopurinol, there was no significant difference among these parameters. In the chlorpromazine group, energy charge and %RxV were higher than in the drug-free group (p less than 0.05). In the OP41483 group, both energy charge and phosphorylation rate were significantly higher (p less than 0.05) and %RxV was significantly high (p less than 0.01) at concentrations of more than 3 nmol/L, compared with the values for those without drugs. These results suggest that the Redoximeter can provide accurate information on the effectiveness of cytoprotective drugs. It is also suggested that OP41483 has potential application for maintaining graft viability for human liver transplantation.

Allopurinol↗

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.

Adenine Nucleotides↗