Arterial Blood Glucose Concentration Research Articles

Physiological and metabolic effects of short-term dopamine reduction in healthy horses using a tyrosine hydroxylase inhibitor (alpha-methyl-para-tyrosine)

Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design. Clinical examination findings were recorded, and blood samples were collected for up to 6 h after administration of AMPT or placebo, for measurement of blood glucose, plasma ACTH and cortisol concentrations, and plasma metabolomic analysis. Plasma prolactin concentration was determined as a proxy index of central dopamine reduction. No adverse clinical effects were detected after oral administration of AMPT, with heart rate, mean arterial pressure and blood glucose concentration not differing between AMPT treatment or placebo. Plasma prolactin concentration peaked 1 h after AMPT administration before returning to baseline at 2 h (for five horses) or 6 h (for one horse). Metabolomic analysis demonstrated a reduction in plasma dopamine (0.72-fold change; P=0.016) 1 h after AMPT treatment. Plasma ACTH and cortisol concentrations were not different between AMPT and placebo over time. A few metabolites associated with ketogenesis were increased, and certain amino acids decreased, at 1 h compared with baseline, for both AMPT treatment and placebo. Therefore, AMPT was effective in reducing both central and circulating dopamine concentrations in healthy horses following a single oral dose. Further pharmacokinetic and pharmacodynamic studies are warranted to optimise the dose and duration of AMPT treatment to achieve longer-term dopamine reduction. Plasma metabolomic findings suggested an interruption to energy flux at the time of sample collection, which may be relevant to nutritional studies in horses and warrants further investigation.

Effects of intravenous ethyl pyruvate on cardiopulmonary variables and quality of recovery from anesthesia in horses

ObjectiveTo determine the effects of intravenous ethyl pyruvate, an anti-inflammatory with putative benefits in horses with endotoxemia, on cardiopulmonary variables during anesthesia and the quality of anesthetic recovery. Study designRandomized, crossover, blinded experimental design. AnimalsA total of six healthy Standardbred geldings, aged 13 ± 3 years and weighing 507 ± 66 kg (mean ± standard deviation). MethodsHorses were anesthetized for approximately 90 minutes on two occasions with a minimum of 2 weeks apart using xylazine for sedation, ketamine and diazepam for induction, and isoflurane in oxygen for maintenance. Lactated Ringer’s solution (LRS; 10 mL kg–1 hour–1) was administered during anesthesia. Treatments were randomized and administered starting approximately 30 minutes after induction of anesthesia and infused over 60 minutes: LRS (1 L) or ethyl pyruvate (150 mg kg–1 in 1 L LRS). Invasive arterial pressures, heart rate, respiratory rate and end-tidal carbon dioxide tensions were recorded every 5 minutes for the duration of anesthesia. Arterial blood gases, glucose and lactate concentrations were measured every 20 minutes. Anesthetic recovery was video recorded, stored, and subsequently rated by two individuals blinded to treatments. Total recovery time, time to extubation, number of attempts and time to sternal recumbency, number of attempts to stand and time to stand were recorded. Quality of recovery was analyzed. Data between treatments and within a treatment were assessed using two-way repeated-measures anova and a Pearson correlation coefficient, significant at p < 0.05. ResultsAll horses completed the study. No significant differences were detected between the ethyl pyruvate and LRS treatments for either the cardiopulmonary variables or quality of recovery from anesthesia. Conclusions and clinical relevanceThe results suggest that intravenous ethyl pyruvate can be administered to healthy anesthetized horses with minimal impact on the cardiopulmonary variables studied or the quality of recovery from anesthesia.

Exogenous surfactant replacement immediately at birth as preventive therapy for lung prematurity in neonatal lambs

Surfactant treatment is a manner to reduce alveolar superficial tension and increase pulmonary compliance in premature neonates. Thus, we aimed to analyze the effect of exogenous surfactant treatment in combination with manual ventilation for preterm lambs. We used 15 ewes and their lambs (n = 16), prematurely born at 135 days. At birth, lambs were submitted to orotracheal intubation attached to a handheld resuscitation device and randomly allocated to: Control Group (n = 5; only manual ventilation), Single Surfactant Group (n = 5; manual ventilation coupled by intratracheal administration of 100 mg/kg surfactant) and Double Surfactant Group (n = 6; surfactant volume was divided into two doses (50 mg/kg + 50 mg/kg) administrated at birth and 30 min thereafter). A complete physical exam, arterial gas analysis, blood glucose, urea and creatinine concentration and chest radiographic assessment were performed at fixed times. All lambs had decreased body temperature until 20 min after birth. However, control and double surfactant groups reached a thermic plateau after 30 min. Regardless of the time-point, control lambs had higher heart rate in comparison to treated neonates, including bradycardia in Single Surfactant Group. Single instillation led to lower oxygenation degree, compared to the Double Surfactant Group, suggesting that surfactant treatment was not able to adequately spread within the alveoli. Lambs treated with surfactant had severe impairment of aerobic activity, leading to anaerobic metabolism. All groups had hypercapnia, which can be explained by inadequate respiratory pattern and pulmonary opacity (89% of the lambs had severe or moderate lung content). In conclusion, exogenous surfactant therapy in association with manual ventilation is ineffective in reverting pulmonary immaturity of the preterm lamb, leading to less vitality, hypoxemia, delayed pulmonary clearance and high mortality rate.

Does Acute Exercise Increase Insulin‐Stimulated Skeletal Muscle Glucose Uptake, Blood Flow And Insulin Signalling In Response To A Meal?

A single bout of exercise increases skeletal muscle insulin sensitivity measured by euglycemic, hyperinsulinemic clamp (EHC) through coordinated increases in skeletal muscle insulin‐stimulated microvascular perfusion and molecular signalling at the level of TBC1D4 (2, 3). Surpringly, however, skeletal muscle interstitial glucose concentration decreases substantially during a EHC, especially after one‐legged exercise, reaching 2–3 mM (1). This result may, however, be a artifact of the EHC because, unlike after a meal, blood glucose does not rise during a EHC but is “clamped” at around 5 mM while plasma insulin is elevated. Therefore, the aim of this project was to determine the effect on leg blood flow and skeletal muscle glucose metabolism of meals begun 4 hours after one‐legged exercise. We hypothesized that hyperglycemia after the meal would prevent a drop in muscle interstitial glucose concentrations and result in large increases in leg glucose uptake. Four healthy young males performed 60 min of 1‐legged knee extensor exercise involving at 80% of 1‐legged peak work load (PWL) with three 5 min intervals at 100% 1‐legged PWL. Participants then rested for 4 hours and catheters were inserted into the femoral artery of one leg and the femoral vein of both legs and two microdialysis catheters for measurement of interstitial glucose concentration were inserted into the vastus lateral muscle of both legs. A solid meal was ingested (40 kJ.kg BW−1) 4 hrs after the 1‐legged exercise with smaller liquid meals (20 kJ.kg BW−1) ingested 4.5 and 5 hrs after the exercise. Four hours after exercise there was no significant difference between the exercised and rested leg for leg blood flow, leg arteriovenous glucose difference, leg glucose uptake, vastus lateralis interstitial glucose concentration or apparent muscle membrane glucose permeability. Meal ingestion increased arterial blood glucose concentration and increased leg blood flow, leg arteriovenous glucose difference and leg glucose uptake more in the exercised leg than the rested leg. Meals increased vastus lateralis interstitial glucose concentration, especially in the rested leg. Vastus lateralis apparent muscle membrane glucose permeability increased with the meals in both legs and moreso in the previously exercised leg. Ingestion of meals several hours after 1‐legged exercise results in hyperglycemia, increased skeletal muscle interstitial glucose concentration and increased muscle membrane permeability to glucose. This results in larger increases in muscle glucose uptake in the previously exercised than the rested leg. Real life feeding after exercise confirms and extends findings from clamp studies.

Effects of Single Dose of Dexamethasone on Perioperative Blood Glucose Levels in Patients Undergoing Surgery for Supratentorial Tumors - An Observational Study.

Introduction:Dexamethasone is commonly administered in intracranial tumors to reduce the cerebral edema. Its administration may be associated with hyperglycemia. The primary objective of this study was to study the magnitude of rise in blood sugar levels following the administration of a single 10 mg dose of dexamethasone.Methods:Seventy patients who underwent various neurosurgical procedures were enrolled in the study. Group D (n = 35 undergoing surgery for intracranial tumors) were administered injection dexamethasone 10 mg while as Group P (n = 35 undergoing surgery for subarachnoid hemorrhage) received placebo. Blood samples were obtained through the arterial line at baseline (before dexamethasone administration), 60, 120, 180, and 240 min after the dexamethasone administration and blood glucose concentrations noted.Results:Glucose concentrations were significantly increased in patients who received dexamethasone compared with those who received placebo (P < 0.05). Blood glucose concentrations at different time intervals were greater when compared with the baseline blood sugar levels in both the placebo and dexamethasone group (P < 0.05). The arterial blood glucose concentration in those who received 10 mg dexamethasone (n = 35) increased from 95.29 ± 13.69 mg.dl−1 to 139.97 ± 10.34 mg.dl−1 over 4 h, compared with a change from 94.74 ± 10.05 mg.dl−1 to 122.34 ± 10.68 mg.dl−1 in those who received placebo (n = 35) (P < 0.05).Conclusion:The administration of a single intravenous dose of 10-mg dose dexamethasone caused a significant increase in the blood glucose concentrations at different point intervals when compared with the placebo over a 4-h period. We recommend intensive monitoring of the blood sugar levels during the intraoperative period to prevent the development of severe hyperglycemia and its associated complications.

The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits

BackgroundGlobal brain ischemia-reperfusion during propofol anesthesia provokes persistent cerebral pial constriction. Constriction is likely mediated by Rho-kinase. Cerebral vasoconstriction possibly exacerbates ischemic brain injury. Because Y-27632 is a potent Rho-kinase inhibitor, it should be necessary to evaluate its effects on cerebral pial vessels during ischemia—reperfusion period. We therefore tested the hypotheses that Y-27632 dilates cerebral pial arterioles after the ischemia-reperfusion injury, and evaluated the time-course of cerebral pial arteriolar status after the ischemia-reperfusion.MethodsJapanese white rabbits were anesthetized with propofol, and a closed cranial window inserted over the left hemisphere. Global brain ischemia was produced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Rabbits were assigned to cranial window perfusion with: (1) artificial cerebrospinal fluid (Control group, n = 7); (2) topical infusion of Y-27632 10−6 mol · L−1 for 30 min before the initiation of global brain ischemia (Pre group, n = 7); (3) topical infusion of Y-27632 10−6 mol · L−1 starting 30 min before ischemia and continuing throughout the study period (Continuous group, n = 7); and, (4) topical infusion of Y-27632 10−6 mol · L−1 starting 10 min after the ischemia and continuing until the end of the study (Post group, n = 7). Cerebral pial arterial and venule diameters were recorded 30 min before ischemia, just before arterial clamping, 10 min after clamping, and 5, 10, 20, 40, 60, 80, 100, and 120 min after unclamping.ResultsMean arterial blood pressure and blood glucose concentration increased significantly after global brain ischemia except in the Continuous group. In the Pre and Continuous groups, topical application of Y-27632 produced dilation of large (mean 18–19%) and small (mean; 25–29%) pial arteries, without apparent effect on venules. Compared with the Control and Pre groups, arterioles were significantly dilated during the reperfusion period in the Continuous and Post groups (mean at 120 min: 5–8% in large arterioles and 11–12% in small arterioles).ConclusionsY-27632 dilated cerebral pial arterioles during reperfusion. Y-27632 may enhance recovery from ischemia by preventing arteriolar vasoconstriction during reperfusion.

Cardiopulmonary effects of pleural insufflation with CO2 during two-lung ventilation in dorsally recumbent anesthetized horses

ObjectiveTo record the cardiopulmonary effects of pleural CO2 positive pressure insufflation in anesthetized horses. Study designProspective study. AnimalsSeven horses (mean ± standard deviation, 530.9 ± 68.1 kg) undergoing terminal surgery. MethodsHorses were sedated with xylazine. Anesthesia was induced with ketamine–propofol and maintained with isoflurane, positive pressure ventilation, detomidine infusion, and butorphanol with the horses in dorsal recumbency. Baseline measurements were cardiac output, heart rate, pulmonary and systemic arterial and right atrial blood pressures, body temperature, expired and inspired gas concentrations, and arterial and mixed venous blood gases, electrolytes, glucose, and lactate concentrations. An 18 gauge 6.6 cm needle was inserted into the right pleural cavity midway between the sternum and dorsal midline in the sixth or seventh intercostal space for pleural pressure (PP) measurement. A 14 gauge 18 cm needle placed 5 cm below the previous needle allowed CO2 insufflation into the pleural cavity. All measurements were repeated after: needle insertion, at 2, 5, and 8 mmHg PPs, and after pleural gas removal (GR). Data were compared with baseline using one-way analysis of variance with repeated measures. p < 0.05 was considered significant. ResultsActual PPs were within 1.1 mmHg of the targeted PP. Pulmonary systolic and mean arterial pressures, alveolar dead space to tidal volume ratio, and isoflurane requirements increased at 8 mmHg PP and GR. Cardiac index decreased at 5 mmHg PP. Stroke index decreased at 2 mmHg PP to GR. PaO2 decreased at 5 mmHg PP to GR. PaCO2 increased at 8 mmHg PP and GR. Oxygen delivery decreased at 5 and 8 mmHg PP. Intrapulmonary shunt fraction and lactate concentration increased with GR. Conclusions and clinical relevance:Severe adverse cardiopulmonary effects arise from CO2 positive pressure insufflation into the right hemithorax in dorsally recumbent isoflurane-anesthetized horses. PP should be ≤2 mmHg.

Assessing the influence of mechanical ventilation on blood gases and blood pressure in rattlesnakes

ObjectiveTo characterize the impact of mechanical positive pressure ventilation on heart rate (HR), arterial blood pressure, blood gases, lactate, glucose, sodium, potassium and calcium concentrations in rattlesnakes during anesthesia and the subsequent recovery period. Study designProspective, randomized trial. AnimalsTwenty one fasted adult South American rattlesnakes (Crotalus durissus terrificus). MethodsSnakes were anesthetized with propofol (15 mg kg−1) intravenously, endotracheally intubated and assigned to one of four ventilation regimens: Spontaneous ventilation, or mechanical ventilation at a tidal volume of 30 mL kg−1 at 1 breath every 90 seconds, 5 breaths minute−1, or 15 breaths minute−1. Arterial blood was collected from indwelling catheters at 30, 40, and 60 minutes and 2, 6, and 24 hours following induction of anesthesia and analyzed for pH, PaO2, PaCO2, and selected variables. Mean arterial blood pressure (MAP) and HR were recorded at 30, 40, 60 minutes and 24 hours. ResultsSpontaneous ventilation and 1 breath every 90 seconds resulted in a mild hypercapnia (PaCO2 22.4 ± 4.3 mmHg [3.0 ± 0.6 kPa] and 24.5 ± 1.6 mmHg [3.3 ± 0.2 kPa], respectively), 5 breaths minute−1 resulted in normocapnia (14.2 ± 2.7 mmHg [1.9 ± 0.4 kPa]), while 15 breaths minute−1 caused marked hypocapnia (8.2 ± 2.5 mmHg [1.1 ± 0.3 kPa]). Following recovery, blood gases of the four groups were similar from 2 hours. Anesthesia, independent of ventilation was associated with significantly elevated glucose, lactate and potassium concentrations compared to values at 24 hours (p < 0.0001). MAP increased significantly with increasing ventilation frequency (p < 0.001). HR did not vary among regimens. Conclusions and clinical relevanceMechanical ventilation had a profound impact on blood gases and blood pressure. The results support the use of mechanical ventilation with a frequency of 1–2 breaths minute−1 at a tidal volume of 30 mL kg−1 during anesthesia in fasted snakes.

Insulin differentially influences brain glucose and lactate in traumatic brain injured patients

Hypo- and hyperglycemia must be avoided to prevent additional brain damage following traumatic brain injury (TBI). However, the optimal blood glucose range requiring insulin remains unknown. Cerebral microdialysis is helpful in unmasking signs of metabolic impairment, thereby identifying deleterious blood glucose levels. A retrospective analysis of prospectively collected cerebral microdialysis samples obtained from 20 non-diabetic patients with severe TBI treated at the trauma surgical intensive care unit at the University Hospital Zürich, Switzerland. The impact of different arterial blood glucose values and concomitant insulin administration on cerebral interstitial glucose and lactate levels was investigated. In addition, energetic impairment was determined by calculating lactate-to-glucose ratios. Insulin administration was associated with significantly reduced cerebral glucose concentrations and significantly increased lactate-to-glucose ratios with arterial blood glucose levels <5 mM. At arterial blood glucose levels >7 mM, insulin administration was associated with significantly increased interstitial glucose values, significantly decreased lactate concentrations, and markedly diminished lactate-to-glucose ratios. Insulin exerts differential effects that depend strongly on the underlying arterial blood glucose concentrations. To avoid energetic impairment, insulin should not be administered at arterial blood glucose levels <5 mM. However, at arterial blood glucose levels >7-8 mM, insulin administration appears to be encouraged to increase extracellular glucose concentrations and decrease energetic impairment reflected by reduced interstitial brain lactate and decreased lactate-to-glucose ratios. Nevertheless, frequent analysis is required to minimize the risk of inducing impaired brain metabolism.

Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury

IntroductionMaintaining arterial blood glucose within tight limits is beneficial in critically ill patients. Upper and lower limits of detrimental blood glucose levels must be determined.MethodsIn 69 patients with severe traumatic brain injury (TBI), cerebral metabolism was monitored by assessing changes in arterial and jugular venous blood at normocarbia (partial arterial pressure of carbon dioxide (paCO2) 4.4 to 5.6 kPa), normoxia (partial arterial pressure of oxygen (paO2) 9 to 20 kPa), stable haematocrit (27 to 36%), brain temperature 35 to 38°C, and cerebral perfusion pressure (CPP) 70 to 90 mmHg. This resulted in a total of 43,896 values for glucose uptake, lactate release, oxygen extraction ratio (OER), carbon dioxide (CO2) and bicarbonate (HCO3) production, jugular venous oxygen saturation (SjvO2), oxygen-glucose index (OGI), lactate-glucose index (LGI) and lactate-oxygen index (LOI). Arterial blood glucose concentration-dependent influence was determined retrospectively by assessing changes in these parameters within pre-defined blood glucose clusters, ranging from less than 4 to more than 9 mmol/l.ResultsArterial blood glucose significantly influenced signs of cerebral metabolism reflected by increased cerebral glucose uptake, decreased cerebral lactate production, reduced oxygen consumption, negative LGI and decreased cerebral CO2/HCO3 production at arterial blood glucose levels above 6 to 7 mmol/l compared with lower arterial blood glucose concentrations. At blood glucose levels more than 8 mmol/l signs of increased anaerobic glycolysis (OGI less than 6) supervened.ConclusionsMaintaining arterial blood glucose levels between 6 and 8 mmol/l appears superior compared with lower and higher blood glucose concentrations in terms of stabilised cerebral metabolism. It appears that arterial blood glucose values below 6 and above 8 mmol/l should be avoided. Prospective analysis is required to determine the optimal arterial blood glucose target in patients suffering from severe TBI.

Lack of agreement between arterial and central venous blood glucose measurement in critically ill children

Dear Sir, We were interested to read the article by Critchell et al. [1] highlighting concerns about the accuracy of bedside capillary blood glucose measurements in critically ill patients. We would agree that the importance of sampling site for blood glucose measurement has been under-emphasized in the published studies on hyperglycaemia and tight glycaemic control. The majority of studies linking hyperglycaemia with adverse clinical outcome have not provided data on the site of sampling. We would like to share preliminary data regarding the use of central venous blood sampling for glucose measurement in critically ill children. The objective of this preliminary study was to compare blood glucose concentrations in simultaneously drawn arterial and central venous blood glucose samples taken for clinical purposes. Paired arterial and central venous blood gas samples were taken to obtain information about oxygen extraction and the results were prospectively documented. Blood glucose was measured on a blood gas analyzer (Bayer Rapidlab; electrochemical biosensor), which is subject to strict quality control by the Clinical Chemistry department. No glucose containing solution was infused into either the arterial or the central venous sampling lines. A total of 245 paired arterial and central venous blood samples were obtained from 71 children, age range 5 days–14 years, between January and October 2006. The majority of cases were children post cardiac surgery, reflecting a group of patients in whom regular assessment of oxygen extraction is undertaken. The median number of samples per patient was 2 (range 1–22). The samples included a wide range of arterial blood glucose values, from 2.4 to 23 mmol/l. There was poor agreement between arterial and central venous blood glucose (Fig. 1). The central venous blood glucose was frequently higher than the arterial blood glucose (median 0.4 mmol/l, CI 0.3–0.5, P \ 0.001 Wilcoxon Signed Rank test). On occasions, the difference exceeded 5 mmol/l. The implications of these findings for titration of insulin therapy are obvious. Inappropriate adjustments to insulin therapy could be made and, importantly, hypoglycaemia could go undetected if central venous sampling is used to monitor blood glucose in this population of critically ill children. It is common for a child to be managed without an arterial line once their cardio-respiratory condition has stabilized, and for bloods to be taken through a central line, if present, to avoid the need for venepuncture. In contrast with our findings, a recent study by Evron et al. [2] found no difference between arterial and central venous blood glucose concentration in adult patients undergoing major orthopaedic or colon surgery though these patients were all studied in the context of general anaesthesia and surgery and were not critically ill. It is possible that glucose containing fluids infused into a vein peripheral to the central venous line or infused via one of the other central venous line lumens could have contaminated the central venous sample that was taken. As this was an opportunistic study performed under uncontrolled conditions information about glucose infusions was not collected, other than confirmation that no glucose containing fluid was infused into either the arterial or central venous sampling lines. However, alternative explanations are possible in that glucose may be generated in peripheral tissues, most notably in muscle, during critical illness and released into the venous system [3, 4]. 0 5 10 15 20 25

A single session of resistance exercise enhances insulin sensitivity for at least 24 h in healthy men

The aim of the present study was to determine whether a single session of resistance exercise improves whole-body insulin sensitivity in healthy men for up to 24 h. Twelve male subjects (23 +/- 1 years) were studied over a period of 4 days during which they consumed a standardized diet, providing 0.16 +/- 0.01 MJ.kg(-1).day(-1) containing 15 +/- 0.1 energy% (En%) protein, 29 +/ -0.1 En% fat and 55 +/- 0.3 En% carbohydrate. Insulin sensitivity was determined 24 h before and 24 h after a single resistance exercise session (8 sets of 10 repetitions at 75% of 1 repetition maximum for two leg exercise tasks) using an intravenous insulin tolerance test. Insulin sensitivity index was calculated by the decline in arterial blood glucose concentration following intravenous administration of a single bolus of human insulin (0.075 IU.kg(-1) fat free mass). Basal glucose and insulin concentrations were not changed up to 24 h after the resistance exercise. However, a substantial 13+/-5% improvement in whole-body insulin sensitivity was observed, 24 h after the resistance exercise (P < 0.05). This study shows that even a single session of resistance exercise improves whole-body insulin sensitivity for up to 24 h in healthy men, which is consistent with earlier observations following endurance exercise tasks.

Control of Exercise-stimulated Muscle Glucose Uptake by GLUT4 Is Dependent on Glucose Phosphorylation Capacity in the Conscious Mouse

Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during exercise because GLUT4 overexpression does not increase exercise-stimulated MGU. Instead of glucose transport, glucose phosphorylation is a primary limitation of exercise-stimulated MGU. It was hypothesized that a partial ablation of GLUT4 would not impair exercise-stimulated MGU when glucose phosphorylation capacity is normal but would do so when glucose phosphorylation capacity was increased. Thus, C57BL/6J mice with hexokinase II (HKII) overexpression (HK(Tg)), a GLUT4 partial knock-out (G4(+/-)), or both (HK(Tg) + G4(+/-)) and wild-type (WT) littermates were implanted with carotid artery and jugular vein catheters for sampling and infusions at 4 months of age. After a 7-day recovery, 5-h fasted mice remained sedentary or ran on a treadmill at 0.6 mph for 30 min (n = 9-12 per group) and received a bolus of 2-deoxy[3H]glucose to provide an index of MGU (Rg). Arterial blood glucose and plasma insulin concentrations were similar in WT, G4(+/-), HKTg, and HKTg + G4(+/-) mice. Sedentary Rg values were the same in all genotypes in all muscles studied, confirming that glucose transport is a significant barrier to basal glucose uptake. Gastrocnemius and soleus Rg were greater in exercising compared with sedentary mice in all genotypes. During exercise, G4(+/-) mice had a marked increase in blood glucose that was corrected by the addition of HK II overexpression. Exercise Rg (micromol/100g/min) was not different between WT and G4(+/-) mice in the gastrocnemius (24 +/- 5 versus 21 +/- 2) or the soleus (54 +/- 6 versus 70 +/- 7). In contrast, the enhanced exercise Rg observed in HKTg mice compared with that in WT mice was absent in HKTg + G4(+/-) mice in both the gastrocnemius (39 +/- 7 versus 22 +/- 6) and the soleus (98 +/- 13 versus 65 +/- 13). Thus, glucose transport is not a significant barrier to exercise-stimulated MGU despite a 50% reduction in GLUT4 content when glucose phosphorylation capacity is normal. However, when glucose phosphorylation capacity is increased by HK II overexpression, GLUT4 availability becomes a marked limitation to exercise-stimulated MGU.

Developmental changes in the activities of aromatic amino acid decarboxylase and catechol- O-methyl transferase in the porcine brain: A positron emission tomography study

Newborn (7–10 days old) and young (6–8 weeks old) pigs were used to study the metabolism of 6-[ 18 F ]fluoro- l-DOPA (FDOPA) in various brain regions with positron emission tomography (PET). Compartmental modeling of PET data was used to calculate the rate constants for the decarboxylation of FDOPA ( k 3) and for the metabolism of the resulting [ 18 F ]fluoro-dopamine ( k cl). Whereas general physiological parameters such as cerebral blood flow, cerebral oxygen uptake, arterial blood gases and glucose concentration remained unchanged in young pigs as compared to newborns, a 50–200% increase of k 3 in frontal cortex, striatum and mesencephalon was found. Also a 60% enhancement of k cl in the frontal cortex was measured, which is related to changes of the catechol- O-methyl-transferase (COMT) activity and implies a special function of this enzyme in the development of this brain region. In addition, measurement of plasma metabolites of FDOPA with HPLC was performed. The metabolism of FDOPA in young pigs was significantly faster than in newborns. Calculation of the rate constant for O-methylation of FDOPA by COMT revealed a significant elevation of this enzyme activity in young pigs compared to newborns. The increase of AADC and COMT activity with brain development is considered to be associated with special stages of neuronal maturation and tissue differentiation.

Insulin requirement in the first 24 hours of intensive care admission predicts outcome

Insulin requirement (in mainly cardiothoracic surgical patients) is suggested as being more strongly associated with ITU mortality than poor glycaemic control [1]. We prospectively recorded insulin administration (soluble human insulin, by infusion; Actrapid®; Novo Nordisk) in consecutive general ITU patients admitted over a 1-month period to our unit where guidelines are set to attempt to achieve an arterial blood glucose concentration between 4.5 and 8.0 mmol/l. Patients were subsequently divided into two groups according to whether or not they required insulin during the first 24 hours. Blood glucose was measured using the Radiometer® ABL System 625 or 700 blood gas analysers. Samples were taken at least every 2 hours. Ninety-eight patients were included in the study: 51 received no insulin, 47 received insulin at some time during the first 24 hours of admission and patients were grouped accordingly. There were no patients with a history of diabetes in the 'no insulin' group and 10 in the 'insulin' group. The mean (SD) number of hours patients who received no insulin were recorded as having a blood glucose > 8.0 was 0.40 (1.41) and for the 47 patients who received insulin 4.74 (4.77). The mean (SD) total insulin dose in the first 24 hours for the 'insulin' group was 38.4 (57.3) IU. Mortality in the 'no insulin' group was 13.1% and in the 'insulin' group 19.1% (chi-square 1.238, P > 0.20). There were no deaths among the previously diagnosed diabetic patients. When these patients were excluded from the analysis the mortality was 13.1% and 32.1%, respectively (chi-square 2.78, P 0.05). The mean (SD) length of stay in the ITU was 4.12 (6.90) days in the 'no insulin' group and 6.77 (8.89) days in the 'insulin' group (one-tailed t test, unequal variance, P = 0.05).

Effects of chronic alcohol consumption on lipid levels, inflammatory and haemostatic factors in the general population: the 'ATTICA' Study.

Epidemiological studies suggest an unclear effect of alcohol consumption on cardiovascular risk. This ambiguity is likely related to the quantity of alcohol consumed in populations studied. The aim of this work was to evaluate the association between chronic alcohol consumption and several clinical and biochemical parameters related to coronary risk, in cardiovascular disease free men and women. The 'ATTICA' study is a population-based cohort, which randomly enrolled 750 men and 883 women (18-88 years old) from area around Athens, during 2001-2002. We investigated the association between alcohol consumption and arterial blood pressure, fibrinogen levels, glucose concentration, total cholesterol, HDL and LDL, apolipoprotein A1 and B, Lp(a), uric acid, leucocyte count, triglycerides, C-reactive protein and homocysteine levels. Multivariate analysis, after controlling for several potential confounders, revealed a J-shaped association between alcohol intake (none, 1-2, 3-4, 5+ wine glasses/day) and uric acid, C-reactive protein, homocysteine, fibrinogen, triglycerides, apolipoproteins A1 and B, HDL and total cholesterols, blood glucose levels, leucocyte count and arterial blood pressure levels (only in males). The most beneficial values of all these biochemical and clinical parameters were found in alcohol intake of 100-200 ml (12% alcohol), even after adjustment for various potential confounders. The controversial association between alcohol intake and cardiovascular disease seems to be partially explained by the J-shaped relation of several biochemical parameters related to atherosclerosis and the amount of alcoholic beverages consumed.

Stress under modernization in indigenous populations of Siberia

Objectives. Arterial blood pressure and serum blood glucose concentration, and the level of anxiety, as determined by the Spielberger test, as physical and psychological markers of stress under “modernization”, were studied in groups of native Siberians: the Khanty and the Mansi.Results. The fraction of respondents with a high level of anxiety is 64% of the total sample. The average values of systolic and diastolic blood pressure are higher among natives living in large than in small “national” settlements (p<0.05). The arterial blood pressure of town dwellers is even higher. The same patterns are seen in the blood serum glucose concentrations in female samples. The average arterial blood pressure (in males and females) and the blood serum glucose concentration (in females) increases as people diverge from “traditional” lifestyles.Conclusions. The results demonstrate that “modernization” and urbanization have a serious stressing influence on the aborigines of North Siberia.

Eliminating discard volumes in neonatal and pediatric blood sampling from arterial catheters: A comparison of three simple blood-conserving aspiration techniques.

OBJECTIVE: To compare different blood aspiration techniques to eliminate discarding of blood in arterial blood sampling from critically ill neonates and children. DESIGN: Prospective, randomized controlled trial. SETTING: A 19-bed tertiary neonatal and pediatric intensive care unit. PATIENTS: Critically ill neonates and children with existing arterial and central venous access. INTERVENTIONS: Paired blood samples were obtained by using conventional blood discarding techniques and one of the following blood-conserving aspiration techniques: passive extracorporeal arteriovenous backflow, free passive backflow to ambient pressure, and active aspiration backflow to a distance of 10 or 20 cm proximal to the sampling port of the arterial pressure catheter. Repetitive conventional sampling served as a control and as the standard. The order of sampling was randomly allocated. We determined arterial blood gases, electrolytes, blood glucose, and hemoglobin concentration. Measurement and RESULTS: Bland-Altman bias analysis of the variability among the techniques revealed that the passive backflow and the active aspiration backflow technique with a backflow distance of 20 cm yielded identical results to repetitive conventional sampling with a standardized discard volume of 0.6 mL. In contrast, the extracorporal arteriovenous backflow technique carried the risk of overestimating blood glucose levels (mean bias, 0.96 mmol/L.). A backflow distance of 10 cm (active aspiration) proved insufficient to eliminate contamination by the catheters' flushing solution. CONCLUSIONS: At a backflow distance of 20 cm, the passive backflow and the active aspiration backflow techniques produce, with the used monitoring set, reliable and precise results in critically ill newborns and children and eliminate discard volumes.

Effects of cyclosporine A and prednisone treatment on mixed meal disposition in dogs with hepatic denervation

Compared with untreated dogs, normal dogs treated for 7 days with cyclosporine A and prednisone exhibited a 25% reduction in the absorption of glucose from a mixed meal and a 4- to 5-fold increase in net hepatic glucose uptake, without reduction of postprandial glycemia. The hepatic nerves are also involved in directing postprandial glucose disposition. Therefore, we hypothesized that the combination of immunosuppressive therapy and hepatic denervation would create additional alterations in the disposition of glucose from a mixed meal. Six 24-hour-fasted conscious dogs that had undergone surgical hepatic denervation (DN) and received cyclosporine A 15 mg/kg daily and prednisone 5 mg twice daily for 7 consecutive days before study (DN + CyP group) received an intragastric mixed-meal feeding over 30 minutes. The results were compared with those from a group of 8 normally innervated dogs receiving the same immunosuppressives (CyP group). Arterial blood glucose concentrations remained elevated over basal in both groups at the end of the 480 minutes postprandial period. The arterial plasma insulin response was no different in the 2 groups (area under the curve 119+/-25 and 100+/-40 nmol/L in DN + CyP and CyP, respectively). In both groups, net gut glucose output was equivalent to approximately 45% of the glucose in the meal, and net hepatic glucose uptake accounted for approximately 54% to 66% of the absorbed glucose. Arterial blood lactate concentrations and net hepatic lactate output were not different between groups at any time. Immunosuppressive therapy is responsible for most of the alterations in postprandial carbohydrate metabolism observed in this model; the lack of hepatic nerves has little additional impact.

Blood Glucose Concentration Measured Using a Glucose Oxidase Method is more Accurate in Venous Blood than Oxygenated Arterial Blood

Background: Portable glucometers are often utilized at the patient's bedside in the ICU or operating room for frequent measurements of the blood glucose concentration. Many of these devices are based on a glucose oxidase method that may be influenced by . The aim of this study was to evaluate the influence of a high of arterial blood on measured glucose values compared with venous blood. Methods: Forty adult patients who underwent surgery with general anesthesia were included in this study. Each patient had a cannula inserted into the radial artery and a central venous catheter through the right internal jugular vein. Two hours after the induction of anesthesia, we drew arterial and venous blood and measured the blood glucose concentration using both a bedside glucometer based on a glucose oxidase method and a laboratory glucometer based on a hexokinase method. We also measured blood gas, electrolyte, and hematocrit values. Statistical analyses were performed with repeated measure ANOVA, multiple linear regression, and Bland-Altman's analysis. Data is expressed as mean . SD. Results: The arterial blood glucose concentration measured by the glucose oxidase method (119.5 25.0 mg/dl) was significantly lower than the venous blood (133.5 24.8 mg/dl) and hexokinase method (134.2 27.1 mg/dl). There was no significant difference between the venous blood glucose concentration by the glucose oxidase method and hexokinase method. When we used the correction formula: corrected glucose value = arterial glucose value by glucose oxidase method + 0.1053 - 5.414, the bias improved from - 14.6 mg/dl to 1.0 mg/dl. Conclusions: The blood glucose concentration measured by the glucose oxidase method is more accurate in venous blood than oxygenated arterial blood. When we measure the blood glucose level using the glucose oxidase method, we should consider the influence of high oxygen tension.