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Biomedical subjects

Y Shimahara

Publications and source records attributed to Y Shimahara.

At least 109 records · Page 6Linked to original sources
PubMed1990

Reduced arterial ketone body ratio during laparotomy: an evaluation of operative stress through the changes in hepatic mitochondrial redox potential.

The present article discusses the evaluation of surgical stress on the basis of the hepatic functional capacity of each patient. The changes in arterial blood ketone body ratio (KBR; acetoacetate/beta-hydroxybutyrate), which reflects hepatic mitochondrial redox potential, following intraoperative procedures were investigated in 60 laparotomy cases, including 30 cases with partial hepatectomy. The time course of changes in KBR was obtained by serial measurement during operation. The total area below the KBR level of 0.7 was defined as the hepatic stress score (HSS). HSS was significantly greater in the cases with hepatectomy (43.5 +/- 9.1; mean +/- SE) than in others (16.5 +/- 4.2; p less than 0.01). HSS in 13 patients accompanied by postoperative complications (60.4 +/- 17.7) was also significantly greater than that in the patients with uneventful postoperative courses (22.1 +/- 4.3; p less than 0.05). The former was also accompanied by significantly larger postoperative catabolic response preceding the clinical onset of complications (p less than 0.001). In the cases with uneventful postoperative courses, analysis of variance revealed that nitrogen balance and catabolic index in the first postoperative week were dependent on HSS negatively and positively, respectively (p less than 0.005), indicating a causative relationship between the suppression of hepatic energy metabolism during operation and the enhanced postoperative catabolic response. These results suggest that total surgical stress in major laparotomy can be quantitated and evaluated through the magnitude of decrease in hepatic mitochondrial redox potential, and that this evaluation may provide valuable information for intraoperative and postoperative patient care.

3-Hydroxybutyric Acid↗
PubMed1989

[The studies on clinical efficacy of Tomiron in the surgical patients: skin and soft tissue infection].

We studied the clinical efficacy and prophylactic effect of Tomiron (cefteram pivoxil; CFTM-PI), a new oral cephalosporin, in the surgical patients. CFTM-PI was administered at a daily dose of 300 or 600 mg after meals. Infectious diseases in 151 patients consisted of infected atheroma, wound infection, subcutaneous abscess, furuncle, phlegmon, mastitis, lymphangitis, periproctal abscess and biliary tract infection. Fifty patients were administered CFTM-PI to prevent secondary wound infection. The clinical efficacy rate was 75.5% in the treatment of infection and 86.0% in the prophylactic use. The clinical efficacy for skin and soft tissue infection was regarded as excellent in 25, good in 74, fair in 17 and poor in 8 out of 124 cases, with a clinical efficacy rate of 79.8%. The eradication rate in 40 cases of monomicro-bial infection was 97.4%, and in 12 cases of polymicrobial infection it was 72.7%. For biliary tract infection, the clinical efficacy was excellent in 1, good in 5, fair in 1 and poor in 1, with a clinical efficacy rate of 75.0%. Adverse effects were observed in 4 (2.0%) of 201 cases: allergic reaction in 3, and sleepiness in 1. Abnormal laboratory findings were observed in 2 cases, but it is not clear if these were due to this drug. These results indicate that Tomiron is a useful oral antimicrobial agent in the treatment and prophylaxis of surgical infection, mainly skin and soft tissue infection.

Adolescent↗
PubMed1989

Influence of hypoxia on mitochondrial function and energy status in CCl4-induced cirrhotic rat liver.

The influence of hypoxia on hepatic mitochondrial function and energy status was studied in normal and carbon tetrachloride (CCl4)-induced cirrhotic rats. Under hypoxemia of 50 mm Hg-PaO2, hepatic energy status was suppressed both in normal and cirrhotic rats. After the reversal of hypoxia, it was completely restored in normal rats concomitant with a rapid elevation of hepatic mitochondrial redox state (overshoot phenomenon) and increase in the mitochondrial oxidative phosphorylative activity. By contrast, in cirrhotic rats, such an enhancement of mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondria have little capacity to respond to the hypoxic stress. A lower resistance to hypoxic episode in cirrhotics might be attributable to the absence of mitochondrial enhancement which is a compensatory mechanism for the deranged energy metabolism of the liver.

Animals↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

Analysis of hemodynamics and blood gas in relation to blood ketone body ratio in partially hepatectomized patients.

A total of 205 studies of hemodynamics and blood gas analyses were performed in relation to hepatic mitochondrial redox state in 23 partially hepatectomized patients. When the blood ketone body ratio (the ratio of acetoacetate to beta-hydroxybutyrate in arterial blood) decreased, that is when the hepatic mitochondrial redox state was reduced, a hyperdynamic state with increased cardiac index, decreased systemic and pulmonary vascular resistance together with decreased oxygen consumption was observed in spite of the increased oxygen availability. Inhibited oxidative metabolism in the Krebs cycle may have resulted in the decreased oxygen consumption and decreased vascular tone. This study supports the concept that the hepatic metabolic derangements due to reduced hepatic mitochondrial redox state may be a factor in the decreased oxygen consumption and hyperdynamic state.

Adult↗
PubMed1989

Significance of hepatic mitochondrial redox potential on the concentrations of plasma amino acids following hemorrhagic shock in rats.

The changes in hepatic energy charge, hepatic mitochondrial redox potential, and plasma amino acid concentrations were examined in rats following the induction of hemorrhagic shock with mean arterial blood pressure at 50 mmHg. Hepatic energy charge and mitochondrial redox potential decreased significantly (P less than 0.001), from 0.86 +/- 0.01 to 0.49 +/- 0.05 and from 14.4 +/- 0.8 to 2.9 +/- 0.6, respectively, at 2 hours after the induction of hemorrhagic shock. Concentrations of total amino acids, alanine, proline, tyrosine, and phenylalanine in plasma increased, and molar ratio [( valine + leucine + isoleucine]/[tyrosine + phenylalanine]) in plasma decreased significantly (P less than 0.001). Hepatic mitochondrial redox potential was correlated negatively with total amino acids (r = -0.90, P less than 0.001) and positively with molar ratio (r = 0.85, P less than 0.001) during hemorrhagic shock. By reinfusion of shed blood at 2 hours after hemorrhagic shock, hepatic energy charge and mitochondrial redox potential immediately recovered to the pretreatment level. However, total amino acids, proline, tyrosine, and phenylalanine increased transiently and thereafter decreased to the pretreatment level. Molar ratio did not recover even at 60 minutes after reinfusion. These results suggest that, in hemorrhagic shock, reduced hepatic mitochondrial redox potential causes inhibition of the citric acid cycle metabolizing the amino acids in the liver and an increase of plasma amino acids; these results suggest also that, in the recovery phase from shock, the restoration of hepatic mitochondrial redox potential is a prerequisite for normalization of the accumulated plasma amino acids.

Adenine Nucleotides↗
PubMed1988

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↗
PubMed1988

Influence of hemorrhagic shock on hepatic energy metabolism in carbon tetrachloride-induced cirrhotic rats.

The influence of hemorrhagic shock on hepatic energy metabolism was investigated in carbon tetrachloride (CCl4)-induced cirrhotic rat. In normal and CCl4-treated rats, the hepatic mitochondrial redox state and phosphorylative activity decreased significantly (P less than 0.001) following hemorrhagic shock, with mean arterial blood pressure at 30 mmHg. In normal rats, they were immediately restored upon reinfusion of shed blood after 2 hr of hemorrhagic shock, followed by marked enhancement 120 min later. By contrast, in cirrhotic rats redox state and phosphorylative activity in hepatic mitochondria did not recover immediately, and there was neither elevation of redox state nor enhancement of phosphorylative activity in hepatic mitochondria. The survival rate at 24 hr was 10% in contrast to 90% in normal rats. These results suggest that the absence of early recovery followed by enhancement of mitochondrial function in the cirrhotic liver is fundamentally related to the mechanism of hepatic failure following hemorrhagic shock.

Adenine Nucleotides↗
PubMed1988

[Metabolic intensive care based on the hepatic mitochondrial redox in hepatectomy].

Intraoperative stress (ISS) in hepatectomy was quantified by the serial measurement of blood ketone body ratio (KBR) during operation. ISS was closely related with the decrease in the postoperative KBR and an enhanced postoperative catabolism. Postoperative urinary 3-methylhistidine level was positively and serum retinol binding protein level was negatively correlated with ISS. Intraoperative stress was closely linked with the postoperative metabolic abnormalities. A key stone in the postoperative management in hepatectomy is to elevate KBR. Utilization of energy substrate in the remnant liver is determined by the KBR level. When the KBR is maintained at higher than 0.7, glucose is predominantly utilized, while free fatty acids utilization increases according to the decrease in the KBR. KBR can be an index in the nutritional support after hepatectomy.

Hepatectomy↗
PubMed1988

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↗
PubMed1988

A simple and direct approach to the portal triad structures for a left lobectomy or a left lateral segmentectomy.

The hilar isolation and dissection of portal pedicle is usually performed prior to hepatectomy in order to minimize blood loss intraoperatively. In some instances, it is difficult to visualize and encircle the bifurcation of the portal triad structures. We recommend the use of a simple and safe method of direct approach to the transverse portion of the portal vein in the left lobectomy or lateral segmentectomy, by incision and dissection of the ligament teres hepatis and continuing fatty tissue.

Common Bile Duct↗
PubMed1987

Fluorometric study for the noninvasive determination of cellular viability in perfused rat liver.

Pyridine nucleotide fluorescence in perfused rat liver for the noninvasive determination of donor graft viability was investigated in relation to other metabolic indices, such as NAD concentration, adenine nucleotides, and mitochondrial phosphorylative activity. The amplitude between oxidation and reduction levels (RxA) in fluorometric trace, and the slope or the velocity of the trace curve from oxidation to reduction (RxV) were determined by the measurement of fluorescence from NAD(P)H, using a new fluorometric device, RxA and RxV decreased proportionally to the duration of preservation period (6, 12, 24, 48 hr) in simple cold storage. Other values of hepatic cell viability, such as total adenine nucleotides, energy charge, and mitochondrial phosphorylation rate, were simultaneously measured and also decreased proportionally to the duration of preservation period. There were close positive correlations between the percentage of RxA and NAD concentration (r = 0.724, p less than 0.01), between the percentage of RxA and total adenine nucleotides (r = 0.887, p less than 0.01), between the percentage of RxV and energy charge (r = 0.715, p less than 0.01), and between the percentage of RxV and phosphorylation rate/cytochrome a(+a3) (r = 0.837, p less than 0.01). These results suggest that this fluorometric method can provide an accurate noninvasive evaluation of donor graft viability--and, unlike the present indices of energy metabolism, it may be applied to evaluate the primary nonfunctioning graft prior to transplantation.

Adenine Nucleotides↗
PubMed1987

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%.

Adenine Nucleotides↗
PubMed1987

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.

3-Hydroxybutyric Acid↗
PubMed1987

Pathophysiology of acute renal failure following living Escherichia coli injection in rats: high-energy metabolism and renal functions.

The energy metabolism of kidney and renal function were studied in rats following an IV injection of living Escherichia coli. Energy charge (ATP + 0.5 ADP/ATP + ADP + AMP) decreased throughout the period studied. Total and ouabain-sensitive Na-K ATPase activity of renal cortex homogenate decreased markedly at 3 hr followed by gradual recovery. Polyulia was seen at 3 and 6 hr followed by oliguria at 12 hr after E. coli injection. PSP excretion test showed a marked decrease throughout the time course. In contrast, creatinine clearance decreased only at 12 hr. From these results, it was clarified that the renal insufficiency following bacteremia occurs in two different stages; the early stage with a high urinary output accompanied by decreased Na-K ATPase activity suggesting deterioration of proximal tubular functions and the late stage with oliguria in which glomerular filtration is severely depressed. In both stages, renal energy metabolism is markedly disturbed.

Acute Kidney Injury↗