Acetoacetate Ratio Research Articles

Probing the dynamic and rehealing behavior of crosslinked polyester networks containing thermoreversible thiol-Michael bonds

A thermoreversible thiol-Michael bond was incorporated into a series of covalently crosslinked polyester networks using base-catalyzed Michael addition polymerization. Variations in acrylate:acetoacetate ratio (crosslink density), thiol-Michael bond content and cure temperature were employed in order to gauge dynamic and rehealing properties. All of the networks investigated in this study were found to display rehealing behavior after being cut at 100 °C within 48 h. Increasing the curing temperature to 120 °C led to a decrease in time to reheal (≤8 h), however the network which employed the highest thiol-Michael bond content, coupled with the lower acrylate:acetoacetate monomer ratio, did not recuperate the original crosslink density upon cooling as evidenced by strain recovery values in excess of 100% and a steady decrease in DSC Tg and TGA weight % as a functional of exposure time.

Influence of Anion and Crosslink Density on the Ionic Conductivity of 1,2,3‐Triazolium‐Based Poly(ionic liquid) Polyester Networks

AbstractCovalently crosslinked, 1,2,3‐triazolium‐containing poly(ionic liquid) networks are prepared using Michael addition polymerization. Crosslink density and counteranion are varied in order to decipher the relationships between poly(ionic liquid) (PIL) structure and their thermal, mechanical, and conductive properties. An increase in acrylate concentration leads to a higher crosslink density, as reflected by an increase in the differential scanning calorimetry Tg, dynamic mechanical analyzer E′, and a decrease in the ionic conductivity. Most notable with variable counteranion PILs is that analysis of the ionic conductivity curves reveals a common “crossover” point at ≈85 °C (same acrylate:acetoacetate ratio). Below this crossover temperature, the ionic conductivity appears to be more dependent upon network/polymer chain dynamics. Above 85 °C, the conductivity correlates best with the size of the counteranion. All of the PILs reported here exhibit good ionic conductivities (10−6 to 10−8 S cm−1@25 °C, 30% RH), supporting the notion that 1,2,3‐triazolium‐containing PILs represent a vastly underrated electroactive material platform.

Spectrum of Clinical Symptoms in Children with Elevated Lactate: Pyruvate Ratio in a Tertiary Care Setting

Introduction: This study is designed to study clinical symptoms in children with elevated lactate: pyruvate ratio to understand the magnitude of respiratory chain disorder. Materials and Method: Children attending pediatric outpatient department in our center who showed clinical symptoms suggestive of inherited metabolic disorder were enrolled into the study. Arterial blood gas, lactate and lactate: pyruvate ratio were analysed by collecting arterial blood from selected children. Clinical symptoms of those children with elevated lactate: pyruvate ratio was evaluated. Result: 304 patients who showed clinical symptoms of either developmental delay without asphyxia, seizures, vomiting, poor suck or weak cry at birth were evaluated. Of them 147 showed one or more of positive biochemical findings such as metabolic acidosis, elevated lactate or lactate: pyruvate ratios which were the basic laboratory data to suspect energy metabolic disorder. Elevated lactate: pyruvate ratio was found in 81 patients, which is one of the biochemical markers to narrow down diagnosis of respiratory chain disorder. Conclusion: Our study showed that suspected energy metabolic disorders are not uncommon. Clinical suspicion is crucial to start further diagnostic profile. Children with delay in attaining milestones despite being born at term without asphyxia need to be referred for metabolic work up. There is a need to create awareness in primary health care providers about this in order to initiate further diagnosis and intervention. Elevated lactate: pyruvate ratio suggests this and warrants further work up. Serum alanine and beta-hydroxy butyrate: acetoacetate ratio may help us to know more about energy metabolic disorders like respiratory chain disorders.

Metabolomic analysis of amino acid and fat metabolism in rats with L-tryptophan supplementation.

Tryptophan (TRP) is an important precursor for several neurotransmitters and metabolic regulators, which play a vital role in regulating nutrient metabolism. The purpose of this study was to investigate the effects of tryptophan supplementation on the biochemical profiles, intestinal structure, liver structure and serum metabolome in rats. Rats received daily intragastric administration of either tryptophan at doses of 200 mg/kg body weight per day or saline (control group) for 7 days. TRP supplementation had a tendency to decrease the body weight of rats (P > 0.05). The levels of urea and CHO in serum were decreased in the TRP-supplemented group rats compared with control group rats (P < 0.05). TRP supplementation increased the villus height and the ratio of villus height to crypt depth in the jejunum compared to control group rats (P < 0.05). Metabolic effects of tryptophan supplementation include: (1) increases in the serum concentrations of lysine, glycine, alanine, glutamate, glutamine, citrulline, methionine, tyrosine, 1-methylhistidine, and albumin, and decreases in the concentrations of serum branched-chain amino acid (isoleucine, valine and leucine); (2) decreases in the serum concentrations of formate and nitrogenous products (trimethylamine, TMAO, methylamine and dimethylamine), and in the contraction of trimethylamine in feces; (3) decreases in serum levels of lipids, low density lipoprotein, very low density lipoprotein, together with the elevated ratio of acetoacetate to β-hydroxybutyrate. The results indicate that tryptophan supplementation reduced the catabolism of dietary amino acids and promoted protein synthesis in rats, promoted the oxidation of fatty acid and reduced fat deposition in the body of rats.

Obligate Role for Ketone Body Oxidation in Neonatal Metabolic Homeostasis

To compensate for the energetic deficit elicited by reduced carbohydrate intake, mammals convert energy stored in ketone bodies to high energy phosphates. Ketone bodies provide fuel particularly to brain, heart, and skeletal muscle in states that include starvation, adherence to low carbohydrate diets, and the neonatal period. Here, we use novel Oxct1(-/-) mice, which lack the ketolytic enzyme succinyl-CoA:3-oxo-acid CoA-transferase (SCOT), to demonstrate that ketone body oxidation is required for postnatal survival in mice. Although Oxct1(-/-) mice exhibit normal prenatal development, all develop ketoacidosis, hypoglycemia, and reduced plasma lactate concentrations within the first 48 h of birth. In vivo oxidation of (13)C-labeled β-hydroxybutyrate in neonatal Oxct1(-/-) mice, measured using NMR, reveals intact oxidation to acetoacetate but no contribution of ketone bodies to the tricarboxylic acid cycle. Accumulation of acetoacetate yields a markedly reduced β-hydroxybutyrate:acetoacetate ratio of 1:3, compared with 3:1 in Oxct1(+) littermates. Frequent exogenous glucose administration to actively suckling Oxct1(-/-) mice delayed, but could not prevent, lethality. Brains of newborn SCOT-deficient mice demonstrate evidence of adaptive energy acquisition, with increased phosphorylation of AMP-activated protein kinase α, increased autophagy, and 2.4-fold increased in vivo oxidative metabolism of [(13)C]glucose. Furthermore, [(13)C]lactate oxidation is increased 1.7-fold in skeletal muscle of Oxct1(-/-) mice but not in brain. These results indicate the critical metabolic roles of ketone bodies in neonatal metabolism and suggest that distinct tissues exhibit specific metabolic responses to loss of ketone body oxidation.

Prooxidant activity of fisetin: Effects on energy metabolism in the rat liver

Flavonols, which possess the B-catechol ring, as quercetin, are capable of producing o-hemiquinones and to oxidize NADH in a variety of mammalian cells. The purpose of this study was to investigate whether fisetin affects the liver energy metabolism and the mitochondrial NADH to NAD+ ratio. The action of fisetin on hepatic energy metabolism was investigated in the perfused rat liver and isolated mitochondria. In isolated mitochondria, fisetin decreased the respiratory control and ADP/O ratios with the substrates α-ketoglutarate and succinate. In the presence of ADP, respiration of isolated mitochondria was inhibited with both substrates, indicating an inhibitory action on the ATP-synthase. The stimulation of the ATPase activity of coupled mitochondria and the inhibition of NADH-oxidase activity pointed toward a possible uncoupling action and the interference of fisetin with mitochondrial energy transduction mechanisms. In livers from fasted rats, fisetin inhibited ketogenesis from endogenous sources. The β-hydroxybutyrate/ acetoacetate ratio, which reflects the mitochondrial NADH/NAD+ redox ratio, was also decreased. In addition, fisetin (200 μM) increased the production of (14)CO2 from exogenous oleate. The results of this investigation suggest that fisetin causes a shift in the mitochondrial redox potential toward a more oxidized state with a clear predominance of its prooxidant activity.

Hepatoprotective action of PGE 1 analogue estimated by measuring the concentrations of acetoacetate and β-hydroxybutyrate

The research was carried out on 56 Chinchilla rabbits. The rabbits were divided into 8 groups with one control group. By means of stomach tube the rabbits were administered respectively: carbon tetrachloride (CCl4), synthetic analogue of prostaglandin misoprostol, CCl4 with misoprostol, indomethacin, misoprostol with indomethacin and CCl4 with misoprostol and indomethacin simultaneously. In order to confirm cytoprotective activity of prostaglandin E1 synthetic analogue in experimental acute hepatocellular damage, we measured in arterial blood the concentration of acetoacetate and beta-hydroxybutyrate and calculated molar ratio of their concentrations. The molar ratio of acetoacetate to beta-hydroxybutyrate which had been calculated for individual groups, regardless of the observed changes in ketone bodies' concentrations, in the case of rabbits which were administered CCl4 with misoprostol, had values similar to the ones obtained for the control group. The smallest value of the ketone body concentration ratio was stated at rabbits which were given only CCl4. The results of the research carried out unambiguously indicate hepatoprotective action of the synthetic analogue PGE1 which was administered to the rabbits.

Disturbances in hepatocellular function during cardiopulmonary bypass using propofol anaesthesia

Background and objective Serum hyaluronate is thought to be an indicator of derangement in hepatocellular integrity, and the change in serum hyaluronate is a useful indicator in various liver disorders. We assessed the changes in serum hyaluronate in patients undergoing coronary artery bypass graft surgery. Methods Eleven patients scheduled for elective coronary artery bypass graft surgery were studied. An oximetry oxygen saturation catheter was inserted into the right hepatic vein to permit monitoring of hepatic venous oxygen saturation. Perioperative measurements included: haemodynamic variables; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; arterial and hepatic venous plasma concentrations of lactate, arterial ketone body ratio (ratio of acetoacetate to 3-hydroxybutyrate); and arterial and hepatic venous hyaluronate were measured. Results Arterial and hepatic venous hyaluronate increased during cardiopulmonary bypass compared with the prebypass period. These increases returned to prebypass values after the cessation of bypass (hepatic venous hyaluronate value at the prebypass period: 26 ± 13 ng mL–1, during bypass: 77 ± 40 ng mL–1; 1 h after bypass: 57 ± 42 ng mL–1; 6 h after bypass: 32 ± 15 ng L–1, 24 h after bypass; 62 ± 21 ng mL–1; mean ± SD, P < 0.05). The arterial and hepatic venous hyaluronate during cardiopulmonary bypass was correlated with total bilirubin and hepatic venous lactate concentrations 6 h after bypass (arterial hyaluronate at cardiopulmonary bypass period vs. total bilirubin at 6 h after bypass;r =0.793, P =0.0036, hepatic venous hyaluronate during bypass vs. that at 6 h after bypass;r =0.795, P =0.0035). Conclusions Hepatocellular integrity might be disturbed during cardiopulmonary bypass when propofol anaesthesia is used.

Disturbances in hepatocellular function during cardiopulmonary bypass using propofol anaesthesia.

Serum hyaluronate is thought to be an indicator of derangement in hepatocellular integrity, and the change in serum hyaluronate is a useful indicator in various liver disorders. We assessed the changes in serum hyaluronate in patients undergoing coronary artery bypass graft surgery. Eleven patients scheduled for elective coronary artery bypass graft surgery were studied. An oximetry oxygen saturation catheter was inserted into the right hepatic vein to permit monitoring of hepatic venous oxygen saturation. Perioperative measurements included: haemodynamic variables; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; arterial and hepatic venous plasma concentrations of lactate, arterial ketone body ratio (ratio of acetoacetate to 3-hydroxybutyrate); and arterial and hepatic venous hyaluronate were measured. Arterial and hepatic venous hyaluronate increased during cardiopulmonary bypass compared with the prebypass period. These increases returned to prebypass values after the cessation of bypass (hepatic venous hyaluronate value at the prebypass period: 26 +/- 13 ng mL(-1), during bypass: 77 +/- 40 ng mL(-1); 1 h after bypass: 57 +/- 42 ng mL(-1); 6 h after bypass: 32 +/- 15 ng L(-1), 24 h after bypass; 62 +/- 21 ng mL(-1); mean +/- SD, P < 0.05). The arterial and hepatic venous hyaluronate during cardiopulmonary bypass was correlated with total bilirubin and hepatic venous lactate concentrations 6 h after bypass (arterial hyaluronate at cardiopulmonary bypass period vs. total bilirubin at 6 h after bypass; r=0.793, P=0.0036, hepatic venous hyaluronate during bypass vs. that at 6 h after bypass; r=0.795, P=0.0035). Hepatocellular integrity might be disturbed during cardiopulmonary bypass when propofol anaesthesia is used.

A Comparison of the Metabolic Effects of Continuous Hypothermic Perfusion or Oxygenated Persufflation during Hypothermic Storage of Rat Liver

The metabolic consequences of supplying oxygen by two different modes were investigated. The effects of hypothermic liver preservation after cold hypoxic flush (Group I), oxygenated vascular persufflation (Group II), and continuous oxygenated perfusion (Group III) were compared. Adenine nucleotides were measured to assess energetics, and 1H nuclear magnetic resonance spectroscopy was employed to investigate other metabolic pathways. Energetics were maintained by both modes of oxygenation at 24 h. The mitochondrial redox state is indicated by the ratio of acetoacetate (Ace) and β-hydroxybutyrate (βHb). The detection of only βHb or Ace in the hypoxic flush and perfused livers, respectively, suggested that the mitochondria of these livers were hyperreduced and hyperoxidized, respectively. In contrast, both components of the redox couple were detected in the persufflated livers, suggesting that persufflation may be a simple and effective method of maintaining hepatic energetics long-term while maintaining a more normal mitochondrial redox state.

Activation of glycolysis by zinc is diminished in hepatocytes from metallothionein-null mice.

The influence of hepatic metallothionein (MT) and zinc (Zn) on glycolysis was investigated in primary cultures of mouse hepatocytes prepared from MT-normal (+/+) and MT-null (-/-) mice. In MT +/+ mice, a close relationship was observed between the Zn concentration in the incubation medium (10-150 microM), increased MT levels in the cells, and increased glycolysis (accumulation of lactate + pyruvate) over 24 h, with significant effects seen at physiological levels of Zn (10-25 microM). Hepatocytes from MT -/- mice had significantly lower basal rates of glycolysis and demonstrated increased glycolysis only at Zn concentrations of 50 microM or greater. The lactate:pyruvate ratio was higher in the MT +/+ hepatocytes. The oxidation of endogenous fatty acid (accumulation of the ketone bodies, 3-hydroxybutyrate and acetoacetate) was initially greater in the MT +/+ hepatocytes, although only MT -/- hepatocytes showed increased ketone body production in response to Zn. The 3-hydroxybutyrate:acetoacetate ratio was higher in the MT +/+ hepatocytes and increased with increasing Zn concentrations. Intracellular Zn accumulation was 60% greater in the MT +/+ hepatocytes, with approximately 80% of the extra Zn associated with MT. The results implicate MT-associated Zn rather than increased intracellular Zn per se in the regulation of hepatic carbohydrate metabolism.

Increased lactate/pyruvate ratio with normal b-hydroxybutyrate/acetoacetate ratio and lack of oxygen supply dependency in a patient with fatal septic shock

We report a case of fatal septic shock, with hyperlactatemia and blood cultures positive for Streptococcus pneumoniae, in a 70-year-old patient. On two occasions (5 days, and 2 days before the patient's death), the relationship between oxygen delivery (DO2) and consumption (VO2) was examined in conjunction with two presumed markers of tissue oxygenation: the lactate/pyruvate ratio (L/P), and the beta-hydroxybutyrate acetoacetate ratio (beta OHB/AcAc). Increasing DO2 by about 30% ("oxygen flux test") failed to increase VO2. The beta OHB/AcAc ratio remained within normal limits, thus suggesting uncompromised tissue oxygenation at the hepatic level. The L/P ratio remained persistently above normal limits, thus suggesting actual organ or regional hypoxia. This case shows that during an overwhelming septic shock, the "oxygen flux test" can be negative, despite the presence of hyperlactatemia and of an increased L/P ratio suggestive of impaired tissue oxygenation.

Increased secretion of triglyceride and cholesterol following inhibition of long-chain fatty acid oxidation in rat liver.

The effects of emeriamine, a fungal metabolite and a potent inhibitor of mitochondrial fatty acid oxidation, on ketogenesis and lipid secretion were examined in isolated perfused livers from 2-day-fasted rats. Liver perfusion with increasing concentrations of emeriamine up to 3 mumol caused a dose-dependent inhibition of ketone body production. The hepatic uptake of exogenous oleic acid substrate was comparable in the control and emeriamine-treated livers. The addition of 2 mumol emeriamine to the perfusion medium at either the beginning of perfusion or 2 h later caused immediate and almost complete cessation of ketone body production, which was accompanied by a concomitant decrease in the beta-hydroxybutyrate: acetoacetate ratio, suggesting a decreased production of NADH via mitochondrial beta-oxidation. Conversely, both triglyceride and cholesterol secretions were elevated, indicating a reciprocal response in ketogenesis and lipid secretion by the livers. The proportion of oleate in the perfusate triglyceride obtained from emeriamine-treated livers was significantly higher than that from control livers. In the post-perfused liver triglyceride, oleate was progressively increased in the livers treated with the inhibitor 2 h after perfusion and at the beginning of perfusion, respectively. These results indicate that direct inhibition of fatty acid oxidation diverts the exogenous fatty acids to the esterification pathway, and subsequently stimulate the synthesis and secretion of triglyceride and cholesterol. The fatty acid oxidation rate in the liver is, therefore, a critical determinant for the synthesis and secretion of these lipid components.

The arterial ketone body ratio and serum alpha-fetoprotein level in patients with acute hepatic failure.

Hepatocyte regeneration is essential for recovery in acute hepatic failure, although it requires a large amount of energy. The ratio of acetoacetate to beta-hydroxybutyrate in arterial blood has been reported to reflect the cellular energy charge of hepatocytes, and we proposed that the recovery of the ratio in the early days of acute hepatic failure is essential for survival. However, there is no report on any marker of regeneration to confirm this hypothesis. In this study, we have assessed this ratio and the serum alpha-fetoprotein level sequentially in 26 patients with acute hepatic failure. Ten patients recovered and 16 died. The arterial blood ketone body ratio 3 days after the onset of hepatic encephalopathy of grade II or more was below 0.6 in 15 of the 16 nonsurvivors, whereas that in the 10 survivors was above 0.6. There was a positive correlation between the arterial blood ketone body ratio and the maximal concentration of alpha-fetoprotein (r = 0.465, p < 0.02 by Student's t-test). These data indicate that the arterial blood ketone body ratio is a marker for the capacity of the liver to regenerate and for the prognosis in patients with acute hepatic failure: effective hepatocyte regeneration may be impossible if these metabolic changes in acute hepatic failure impair the hepatocyte energy charge severely.

Differential effects of geometrical isomers of octadecadienoic acids on ketogenesis and lipid secretion in the livers from rats fed a cholesterol-enriched diet.

The effect of cis,cis (cc)- and trans,trans (tt)-9,12-octadecadienoic (18:2) acids on ketogenesis and lipid secretion was compared in isolated perfused livers from cholesterol-fed rats. The hepatic uptake of 18:2 acids was comparable in both isomers. The livers perfused with cc-18:2 acid in comparison with those perfused without fatty acid substrate produced approximately 4-fold more ketone bodies accompanying the rise of the beta-hydroxybutyrate:acetoacetate ratio, while the tt-acid isomer further increased these parameters. The hepatic secretion rates of triglyceride and phospholipid as well as cholesterol were all elevated on perfusing the cc-18:2 acid as compared to without fatty acid. In contrast, the rates observed with the tt-18:2 acid isomer except for phospholipid were intermediate, indicating a reciprocal response in ketogenesis and lipid secretion by the trans isomer. The rate of incorporation of trans-fatty acid into perfusate triglyceride and cholesterol ester were lower than cis-acid, but vice versa into perfusate phospholipids. On the other hand, the effects of trans-fatty acid on the concentration and composition of hepatic lipids were less clear. These results emphasize the differential effect of geometrical isomers of the 18:2 acids on oxidation and esterification even in the livers containing a high level of cholesterol.

Monitoring of hepatic venous oxygen saturation for predicting acute liver dysfunction after Fontan operations

Acute liver dysfunction after Fontan operations may result from inadequate hepatic perfusion along with low cardiac output and high central venous pressure. We monitored hepatic venous oxygen saturation in 15 patients after Fontan operations to determine whether oxygen saturation predicts the occurrence and severity of acute liver dysfunction. We measured oxygen saturation from hepatic venous blood samples every 4 to 5 hours for at least 24 hours after the operation and used the mean hepatic venous oxygen saturation value for the first 24 hours after the operation to analyze the relationship between oxygen saturation and hepatic function. As indices of hepatic function, we measured serum alanine aminotransferase, total bilirubin, blood lactate (arterial, hepatic venous, and the difference between them), and the arterial ketone body ratio (the ratio of aceto-acetate to β-hydroxybutyrate). For alanine aminotransferase and bilirubin, we used the maximal values during the first week in the analysis, and for blood lactate and ketone body ratio, we used the mean values for the first 24 hours after the operation. Significant broken-line regression relationships existed between mean hepatic venous oxygen saturation and hepatic function indices (alanine aminotransferase, total bilirubin, and blood lactate). The interpretation of these relationships is that hepatic indices are constant above the critical mean hepatic venous oxygen saturation values but are correlated with mean hepatic venous oxygen saturation below critical points in the range of 21% to 26%. Thus a hepatic venous oxygen saturation value below about 25% during the first 24 hours after a Fontan operation predicts the occurrence and the severity of acute liver dysfunction. We suggest that monitoring hepatic venous oxygen saturation is useful for management of critically ill patients after Fontan operations. (J THORAC CARDIOVASC SURG 1994;108:700-8)

Plasma exchange and the arterial blood ketone body ratio in patients with acute hepatic failure

Hepatocyte regeneration in acute hepatic failure is essential for recovery, but requires a large amount of energy. One problem with plasma exchange as supportive therapy in these cases is that massive citrate infusion has an adverse effect on the hepatic energy charge, which may be a serious risk in these patients. The ratio of acetoacetate to beta-hydroxybutyrate in arterial blood has been reported to reflect the cellular energy charge of hepatocytes. In this study, this ratio was assessed before and after plasma exchange in 19 patients with acute hepatic failure. Eight patients recovered and 11 died. The arterial blood ketone body ratio was below 0.6 in all 11 nonsurvivors. It fell to below 0.4 in 10 of them during the first plasma exchange session, and remained below 0.4 for over 12 h in seven of them. On the other hand, the arterial blood ketone body ratio returned to above 0.6 in four of eight surviving patients within 12 h after the first plasma exchange and remained below 0.4 for over 12 h only in two of eight patients. These data indicate that plasma exchange may cause suppression of the arterial ketone body ratio in patients with severe acute hepatic failure. These metabolic changes impair liver metabolism and may make effective hepatocyte regeneration impossible.

The Changes of Arterial Ketone Body Ratio and Osmolal Gap during Hemorrhagic Shock in Rabbit

The ratio of acetoacetate to 8-hydroxybutyrate (ketone body ratio) in the blood may reflects the mitochondrial free NAD+/NADH ratio in the liver. Also arterial ketone body ratio will reflects the energy status of the hepatocytes, because mitochondrial free NAD+/NADH ratio is closely related to oxidative phosphorylation. Arterial ketone body ratio and osmolal gap, the difference between measured osmolality and calculated osmolality, were measured 30 min after the induction of hemorrhagic shock with mean arterial blood pressure at 40 mmHg in ten rabbits. Arterial ketone body ratios decreased significantly (p<0.05) from 0.74±0.17 to 0.38±0.09 and osmolal gap increased significantly (p<0.05) from 17.7±5.9 mOsm/Kg to 32.8±12.3 mOsm/Kg at 30 min after the induction of hemorrhagic shock. These results suggest that in hemorrhagic shock, decreased arterial ketone body ratio which reflects the inhibition of the TCA cycle is associated with increase of osmolal gap.

Delayed oxidation of intramitochondrial pyridine nucleotide oxidoreduction state as compared with tissue oxygenation in human liver transplantation

Intra- and post-operative oxygenation of graft liver and subsequent oxidation of the intramitochondrial oxido-reduction state of pyridine nucleotide were studied in partial liver transplantation from living related donors with the ratio of acetoacetate to β-hydroxybutyrate in arterial blood (AKBR), the ratio of oxidized flavoprotein to reduced pyridine nucleotide (FP/PN ratio) and oxygen saturation of hemoglobin in liver tissue (hepatic SO 2). Decreased hepatic SO 2 and its heterogenous distribution after reflow of portal vein and hepatic artery were normalized by the end of operation, while the intramitochondrial oxido-reduction state was still reduced at the end of operation and was normalized only at 24 h after the operation. The observed delay in oxidation of the intramitochondrial oxido-reduction state as compared with tissue oxygenation indicates the transition of the intramitochondrial oxido-reduction state associated with the initiation of metabolic activity from the cold preserved state, and suggest an important role for microcirculation in the normalization of the oxido-reduction state.

Changes in the parameters of oxygen metabolism in a clinical course recovering from potassium cyanide

Poisoning with potassium cyanide is usually fatal because of the inhibition of cytochrome oxidase. The parameters of oxygen metabolism in a patient with cyanide poisoning who was admitted in a coma with seizures was monitored. The administration of amyl nitrite and sodium thiosulfate led to a rapid improvement: the parameters reflecting oxygen metabolism improved and the plasma level of cyanide decreased. The patient revived 1 1 2 hours after treatment. The arterial ketone body ratio (AKBR), which is the ratio of acetoacetate to beta-hydroxybutyrate in arterial blood and which refiects the redox state in liver mitochondria, improved dramatically following treatment. Because the AKBR changes in relation to electron transport in liver mitochondria, it seems to be a logical parameter for evaluating the effect of potassium cyanide poisoning on electron transport. The AKBR also reflects the efficacy of treatment for cyanide poisoning.