Association of higher arterial ketone body ratio (acetoacetate/ß-hydroxybutyrate) with relevant nutritional marker in hemodialysis patients.

BACKGROUND: An association of higher levels of ß-hydroxybutyrate (ß-HB) in serum with greater mortality in hemodialysis (HD) patients has been reported. This study examined the significance of arterial ketone body ratio (AcAc/ß-HB), a relevant marker of energy state, in HD patients. METHODS: The levels of arterial AcAc and ß-HB, and AcAc/ß-HB ratio were determined in 49 HD patients just before undergoing an HD session. Additionally, changes in those levels during the session were examined to investigate their associations with clinical nutritional markers. RESULTS: Arterial ß-HB, but not AcAc, was significantly higher at the baseline in 25 patients with type 2 diabetes mellitus (T2DM) as compared to 24 non-DM patients, with a significant reduction in arterial AcAc/ß-HB ratio seen in those with DM. Although the arterial AcAc/ß-HB ratio before the HD session was significantly higher in the non-DM group, it did not differ significantly after the session between the groups, indicating a faster rate of ß-HB disappearance from circulation in non-DM HD patients during the interdialytic period. Multiple regression analysis, which included age, gender, presence/absence of DM, log HD duration, log ß-HB, and log AcAc/ß-HB ratio as independent variables, revealed an independent and significant association of log AcAc/ ß-HB ratio, but not log ß-HB, with serum albumin and uric acid. CONCLUSION: We found that a decreased AcAc/ß-HB ratio resulting from increased ß-HB, but not increased ß-HB itself, was a significant factor independently associated with decreased levels of serum albumin and uric acid, known to be related to higher mortality in HD patients. Furthermore, it is possible that higher mortality in DM HD patients can be explained by reduced arterial AcAc/ß-HB ratio.

Ischemic Preconditioning Preserves Liver Energy Charge and Function on Hepatic Ischemia/Reperfusion Injury in Rats.

BACKGROUND: Cell energy during ischemia/reperfusion depends on mechanisms including adenosine diphosphate degradation, oxygen species and cytokine liberation, neutrophil infiltration, and endothelial dysfunction. Preconditioning-a brief ischemic episode that confers a state of protection against subsequent ischemia-reperfusion injury-involves NO and adenosine production, reduction in oxygen species liberation, and preservation of microcirculation. During hypoxia, constitutive NO production assures adequate oxygen delivery and reduced energy loss. The aim was to determine the role of ischemic preconditioning in the stimulation of constitutive endothelial nitric oxide (NO) production and its effect on energy charge, radical oxygen species generation, cytokine liberation, and neutrophil infiltration during reperfusion. MATERIALS AND METHODS: Rats were assigned to one of four groups depending on the preconditioning protocol: hepatic ischemia/reperfusion, or hepatic ischemia/reperfusion and ischemic preconditioning, for 5, 10, or 20 min. A portosystemic shunt was established between the portal and left jugular veins during ischemia. RESULTS: Preconditioning produced rises in plasma nitrites, but no rise in inducible nitric oxide synthase gene expression. A 5 or 10 min preconditioning period allowed for higher energy charge, bile production, and glutathione levels, with less lipoperoxide, alanine aminotransferase, tumor necrosis factor-α, and interleukin-1 production and neutrophil infiltration, compared with 20 min or control. Survival was 80% in the G10 group, 70 in G5, 10 in GC, and 0% in the G20 group. CONCLUSIONS: Ten-min liver preconditioning improves survival and prevents energy loss during hepatic ischemia/reperfusion by stimulating constitutive NO production, maintaining glutathione concentrations and reducing oxygen species and proinflammatory cytokine generation as well as neutrophil infiltration.

Effect of different doses of propofol and propofol medium/long-chain fat emulsion on blood ketone body ratio / 临床麻醉学杂志

Objective To observe the effect of different doses of propofol injection and propofol medium/long-chain fat emulsion injection in short time infusion on plasma ketone body ratio,to eva-lute its effecton hepatic energy metabolism.Methods Forty patients,aged 18-50 years old,ASA Ⅰ orⅡ undergoing selective surgery were randomly divided into 4 groups with 10 cases in each;propofol injection 4 mg·kg-1·h-1 maintain anesthesia (group L4 ),propofol injection 6 mg·kg-1·h-1 maintain anesthesia (group L6 ),propofol medium/long-chain fat emulsion injection 4 mg·kg-1·h-1 maintain anesthesia (group M4 ),propofol medium/long-chain fat emulsion injection 6 mg·kg-1·h-1 maintain anesthesia (group M6 ).MAP,HR,SpO2 and PET CO2 were recorded before anesthesia induction (T0 ),after tracheal intubation (T1 ),after 2 hours infusion of propofol (T2 )and operation completed (T3 ).The blood samples were collected at T1 and T2 to detect the level of acetoacetate,β-hydroxybu-tyrate and to calculate the blood ketone body ratio (the ratio of acetoacetate andβ-hydroxybutyrate). Results MAP,HR,SpO2 ,PET CO2 at T0-T3 and acetoacetate,β-hydroxybutyrate,blood ketone body ratio at T1 ,T2 showed no significant statistic difference.Conclusion Different doses of propofol and different doses of propofol medium/long-chain fat emulsion injection in short time continuous in-fusion has no obvious effect on hepatic energy metabolism;same dose of propofol injection and propo-fol medium/long-chain fat emulsion injection in short time continuous infusion has no obvious effect on hepatic energy metabolism.

Changes of arterial blood ketone body ratio following hypoperfusion in old and adult rats / 老年心脏病学杂志（英文版）

Objective To evaluate the sensitivity of arterial ketone body ratio as an indicator for multiple organ failure.Materials and methods The experimental model of multiple organ failure was made in adult and old rats by hypoperfusion-induced hemorrhagic shock. After blood sampling, the arterial acetoacetate, β-hydroxybutyrate, total ketone body, ALT, AST, BUN, creatinine at 2, 4, 8 hr in hypoperfusion were examined to compare the differences of ketone body ratio and organ failure between adult and old rats. Hepatic and mitochondrial metabolism were assessed by comparing ketone body ratios (AcAc/β-OHB) and free NAD+/NADH ratios. Results Ketone body ratio in old rats at 2, 4, 8 hr after the induction of hemorrhagic shock decreased from 0.68 to 0.31, 0.27 and 0.22, respectively. In adult rats, it decreased from 1.12 to 0.17, 0.12 and 0.09, respectively. Changes of ketone body ratio in the adult group were larger than in the elderly group ( P ＜ 0.001). The development of multiple organ failure is associated with the time of hemorrhagic shock development. Conclusions There was a different ketone body ratio between multiple organ failure in the elderly (MOFE) and multiple organ failure (MOF) in general adults. Ketone body ratio is a better indicator than ALT and AST in reflecting hepatic function in the early status of MOF. (J Geriatr Cardiol 2004;1(2) :125-128. )

Predictive Comparisons of Procalcitonin (PCT) Level, Arterial Ketone Body Ratio (AKBR), APACHE III Score and Multiple Organ Dysfunction Score (MODS) in Systemic Inflammatory Response Syndrome (SIRS)

Procalcitonin (PCT) is a newly introduced marker of systemic inflammation and bacterial infection. A marked increase in circulating PCT level in critically ill patients has been related with the severity of illness and poor survival. The goal of this study was to compare the prognostic power of PCT and three other parameters, the arterial ketone body ratio (AKBR), the acute physiology, age, chronic health evaluation (APACHE) III score and the multiple organ dysfunction score (MODS), in the differentiation between survivors and nonsurvivors of systemic inflammatory response syndrome (SIRS). The study was performed in 95 patients over 16 years of age who met the criteria of SIRS. PCT and AKBR were assayed in arterial blood samples. The APACHE III score and MODS were recorded after the first 24 hours of surgical ICU (SICU) admission and then daily for two weeks or until either discharge or death. The patients were divided into two groups, survivors (n=71) and nonsurvivors (n=24), in accordance with the ICU outcome. They were also divided into three groups according to the trend of PCT level: declining, increasing or no change. Significant differences between survivors and nonsurvivors were found in APACHE III score and MODS throughout the study period, but in PCT value only up to the 7th day and in AKBR only up to the 3rd day. PCT values of the three groups were not significantly different on the first day between survivors and nonsurvivors. Receiver operating characteristic (ROC) curves for prediction of mortality by PCT, AKBR, APACHE III score and MODS were 0.690, 0.320, 0.915 and 0.913, respectively, on the admission day. In conclusion, PCT could have some use as a mortality predictor in SIRS patients but was less reliable than APACHE III score or MODS.

The Effects of Acute Normovolemic Anemia Induced by Hemodilution on Tissue Oxygenation in Dogs: A Comparison of Systemic Oxygen Consumption, Arterial Lactate, Arterial Ketone Body Ratio and Gastric Intramucosal pH / 대한마취과학회지

BACKGROUND: The reduction in hematocrit (Hct) by hemodilution tends to cause an increase in cardiac output and a proportional decrease in arterial oxygen content. Additionally the reduction of systemic oxygen delivery (DO2) leads to significant differences in regional blood flow. It is therefore important to characterize the effects of hemodilution on regional oxygen metabolism in individual organs. This study was undertaken to evaluate and compare the effects of acute normovolemic anemia induced by hemodilution. METHODS: Six dogs were anesthetized and mechanically ventilated. Catheters were inserted in the right femoral and pulmonary arteries for blood sampling, and a gastric tonometer catheter was inserted into the gastric lumen. Baseline measurements of systemic hemodynamics, arterial ketone body ratio (AKBR), gastric intramucosal pH (pHi) and arterial lactate were recorded. Hemodilution was then begun by 6% pentastarch and was made in four levels of hematocrit values of 20%, 15%, 10% and 6%. RESULTS: Mean arterial pressures of Hct 10% and 6% was decresaed (P < 0.05) and Hct 15% and 10% increases in cardiac output and pulmonary capillary wedge pressure (PCWP) were observed. Central venous pressure and mean pulmonary arterial pressure were incresed (P < 0.05) at Hct 15%, 10% and 6%. DO2 progressively decreased (P < 0.05). AKBR and pHi began to decreased at Hct 15%. Arterial lactate decrease at Hct 15% and was above 7.4 mmol/L at Hct 6%. CONCLUSIONS: By the measurements of AKBR and pHi, the disturbance of splanchnic oxygenation can be detected early compared to those of O2 in terms of oxygen metabolism and the critical point of DO2 during acute normovolemic anemia induced by hemodilution.

Clinical Significance of Several Hepatic Function Tests in Hepatectomized Patients / 한국간담췌외과학회지

BACKGROUND/AIMS: To reduce the rate of recurrence and to prevent postoperative liver failure, it is necessary to determine the extent of hepatic resection preoperatively in primary liver cancer patients. The aim of this study was to examine the clinical significance and correlation among several preoperative liver function tests. METHODS: Twenty-nine patients who underwent hepatic resection for hepatocellular carcinoma from November 1994 to March 1995 at the Department of Surgery, Seoul National University Hospital were analyzed. Fifteen patients had gross cirrhosis. Major resections were performed in two patients, segmentectomy in 6 patients, subsegmentectomy and limited resection in 21 patients. Maximal removal rate of indocyanine green (ICG Rmax), ICG retention rate at 15 min(ICG R15), oral glucose tolerance test(oral GTT), arterial ketone body ratio(AKBR) and computed tomographic volumetry, as well as conventional liver function test and prothrombin time were done preoperatively. RESULTS: There were significant correlations among Child's class, prothrombin time and ICG R15. AKBR, oral GTT, ICG Rmax, liver volume had no correlations with any other tests. Liver failure occurred in 2 patients(6.9%). No tests, except ICG R15, could predict the patients with liver failure. ICG R15 value of these two patients were 27% and 29%, respectively while those of the remaining 27 patients ranged from 1 to 22% (mean 11.9%). CONCLUSION: Neither standard liver function tests nor hepatic function studies such as AKBR, oral GTT, CT volumetry were useful as preoperative prognostic indicators in hepatic resection. ICG R15 test is a simple test and good predictor of liver failure after hepatic resection.

Study on Hepatic Injury following Occlusion of Hepatic Inflow in Rabbits / 대한마취과학회지

BACKGROUND: Portal triad clamping was first described by Pringle in 1908 as a mean of reducing bleeding from the cut surface of the liver during parenchymal resection. More recently some studies have reported that one period of portal triad clamping could be well tolerated for a longer duration, 60~90 minutes. The liver, generally, is believed to be very sensitive to anoxic damage and susceptible to ischemia and decreased hepatic energy charge results in decreasing arterial ketone body ratio (AKBR) during portal triad clamping. METHODS: In order to observe an adverse effects to liver in 30 minutes and 60 minutes of portal triad clamping on AKBR and histologic changes,rabbits were divided into thirty minutes of portal triad clamping in one group (Group I) and 60 minutes of that in the other group (Group II). RESULTS: During clamping, the mean AKBR of group I and II were 0.39 and 0.44, and decreased significantly compared with the mean AKBR (1.08 and 1.02) before clamping. Five minute after declamping, the mean AKBR of group II (0.49) was lower (P0.05). Under light microscopic examination of liver biopsy, there was no visible diffrences between two groups during clamping, 5 minutes and 30 minutes after declamping. CONCLUSIONS: It was concluded that there was no difference in hepatic energy change(AKBR) and histologic change under light microscopy after 30 minutes declamping between two groups.

Protection of Hepatic Dysfunction during and after Hemorrhagic Shock with Intravenous Glutathione in Dogs / 대한마취과학회지

During hemorrhagic shock, liver is susceptible to ischemia and decreased hepatic energy charge results in decreasing arterial ketone body ratio(AKBR). Reperfusion after hemorrhagic shock can greatly amplify the generation of toxic oxygen metabolites. As a result, the fluxes of these highly toxic metabolites can overwhelm the endogenous antioxident defense mechanisms and lead to tissue injury. In order to observe the effect of glutathione(GSH) on the AKBR in hemorrhagic shock, dogs(n=16) were anesthetized with 1% enflurane in 02. We pretreated glutathione (100 mg/kg) intravenously before hemorrhagic shock in glutathione (GSH) group (n=8). Shock was induced with bleeding and mean arterial pressure was maintained 50 mmHg for 30 minutes. Recovery from shock was done with transfusion of preserved blood and maintained for 30 minutes. We measured arterial ketone bodies and ketone body ratio before, during and after shock, and compared them to control group (n=8) which was not pretreated with glutathione. AKBR during and after hemorrhagic shock in GSH group (0.8 and 1.0) were higher than those in control group (0.5 and 0.8). Light microscopic examination of liver biopsy revealed less portal degeneration during and after hemorrhagic shock in GSH group than control group. Pharmacologic modulation of hepatocytic function with glutathione before hemorrhagic shock has shown some beneficial effect with protection of decreased AKBR and histological change during and after hemorrhagic shock.

The Effects of Glutathione and Prostaglandin E1 on Recovery of Hepatic Function during Hepatic Ischemia and Reperfusion in Rabbits / 대한마취과학회지

The interruption of hepatic blood flow has been adopted as a method of bleeding control in hepatectomy and liver transplantation. But this occlusion of hepatic inflow may result in significant hepatic injury by various kinds of oxygen radicals produced as a result of hepatic ischemia and following reperfusion. Arterial ketone body ratio(AKBR) is adequatc and convenient parameter by which both acute and prolonged changes of the hepatic function can be estimated. Pharmacological modulation of hepatic injury during warm ischemia and early reperfusion has shown some benefical effects. The authors conducted an experiment to evaluate the inhibitory effect of glutathione and prostaglandin E on hepatic injury due to acute hepatic ischemia and reperfusion. Thirty rabbits were divided into three groups, such as control(n=10), GSH(n=10) and PGE(n=10) groups. Acute hepatic ischemia was induced through the application of portal triad cross-clamping for 30 minutes, and thereafter hepatic reperfusion was induced with the removal of cross-clamping. A single bolus of 200 mg glutathione was injected 10 min before clamp in GSH group, and 200 ng/kg/min of PGE continuously from 10 min before clamp to 30 min after declamp in PGE group. AKBR and hepatic histological findings hefore clamp, 30 min after clamp, 5 min and 30 min after declamp, respectively were compared among 3 groups AKBR was markedly decreased during the clamping period in all groups (P<0.05). In control and PGE groups AKRR was significantly increased after reperfusion than before clamp (P<0.05), but was significantly lower than before clamp. Thirty minutes after reperfusion in GSH group AKBR returned to normal level and was significantly higher than in control group (P<0.05). On light tnicroscopic examination of liver biopsy, mild swollen hepatocytes in the centrilobular zone were seen at ischemia and reperfusion in control and GSH groups, but nearly normal hepatic architectures in PGE group. These results suggest that glutathione has some benefical effect on protection of hepatic dysfunction, and PGE1 on protection of hepatocellular injury during hepatic ischemia and reperfusion.

Effect of prostaglandin E1 on arterial ketone body ratio in hepatectomy.

We evaluated the effect of prostaglandin E1 (PGE1) administration during hepatectomy on arterial ketone body ratio (AKBR), which is an indicator of liver function, and on other liver functions in the postoperative period. Eighteen patients were divided into two groups: Continuous intravenous administration of PGE1 (0.02 µg·kg-1·h-1) was started immediately before hepatic resection and ceased at the end of operation in nine patients (PGE1 group); the other nine did not receive PGE1 (control group). After hepatic resection, a significant increase in AKBR was observed in the PGE1 group. However, no change was observed in the control group. In the PGE1 group, total bilirubin and SGOT recovered more rapidly to the preoperative level than in the control group. These findings suggested that PGE1 might have a protective effect on the liver.

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

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.