Search

INTRODUCTION: Despite advances in treatment of patients with cardiogenic shock following acute myocardial infarction (AMICS) in-hospital mortality remains around 50%. Outcome varies among patient subsets and the elderly often have a poor a priori prognosis. We sought to investigate outcome among elderly AMICS patients referred to evaluation and treatment at a tertiary university hospital. METHODS: Current analysis was based on the RETROSHOCK registry comprising consecutive AMICS patients admitted to tertiary care. Patients in the registry were individually identified and validated. RESULTS: Of 1,716 admitted patients, 496 (28.9%) patients were ≥75 years old. Older patients were less likely to be admitted directly to a tertiary centre (59.4% vs. 69.9%, P = 0.003), receive mechanical support devices (i.e., Impella® (8.9% vs. 15.0%, P = 0.003), and undergo revascularization attempt (76.8% vs. 90.2%, P

Preterm birth (PTB) is a leading global cause of infant mortality. Risk factors include genetics, lifestyle choices and infection. Understanding the mechanism of PTB could aid the development of novel approaches to prevent PTB. This study aimed to investigate the metabolic biomarkers of PTB in early pregnancy and the association of significant metabolites with participant genotypes. Maternal sera collected at 16 and 20 weeks of gestation, from women who previously experienced PTB (high-risk) and women who did not (low-risk controls), were analysed using 1H nuclear magnetic resonance (NMR) metabolomics and genome-wide screening microarray. ANOVA and probabilistic neural network (PNN) modelling were performed on the spectral bins. Metabolomics genome-wide association (MGWAS) of the spectral bins and genotype data from the same participants was applied to determine potential metabolite-gene pathways. Phenylalanine, acetate and lactate metabolite differences between PTB cases and controls were obtained by ANOVA and PNN showed strong prediction at week 20 (AUC = 0.89). MGWAS identified several metabolite bins with strong genetic associations. Cis-eQTL analysis highlighted TRAF1 (involved in the inflammatory pathway) local to a non-coding SNP associated with lactate at week 20 of gestation. MGWAS of a well-defined cohort of participants highlighted a lactate-TRAF1 relationship that could potentially contribute to PTB.

Following activation, conventional T (T-conv) cells undergo an mTOR-driven glycolytic switch. Regulatory T (T-reg) cells reportedly repress the mTOR pathway and avoid glycolysis. However, here we demonstrate that human thymus-derived T-reg (tT(reg)) cells can become glycolytic in response to tumour necrosis factor receptor 2 (TNFR2) costimulation. This costimulus increases proliferation and induces a glycolytic switch in CD3-activated tT(reg) cells, but not in T-conv cells. Glycolysis in CD3-TNFR2-activated tT(reg) cells is driven by PI3-kinase-mTOR signalling and supports tT(reg) cell identity and suppressive function. In contrast to glycolytic T-conv cells, glycolytic tT(reg) cells do not show net lactate secretion and shuttle glucose-derived carbon into the tricarboxylic acid cycle. Ex vivo characterization of blood-derived TNFR2(hi)CD4(+)CD25(hi)CD127(lo) effector T cells, which were FOXP3(+)IKZF2(+), revealed an increase in glucose consumption and intracellular lactate levels, thus identifying them as glycolytic tT(reg) cells. Our study links TNFR2 costimulation in human tT(reg) cells to metabolic remodelling, providing an additional avenue for drug targeting.

Background: Data suggests that the plasma levels of the liver-specific miR-122-5p might both be a marker of cardiogenic shock and a prognostic marker of out-of-hospital cardiac arrest (OHCA). Our aim was to characterize plasma miR-122-5p at admission after OHCA and to assess the association between miR-122-5p and relevant clinical factors such all-cause mortality and shock at admission after OHCA. Methods: In the pilot trial, 10 survivors after OHCA were compared to 10 age- and sex-matched controls. In the main trial, 167 unconscious survivors of OHCA from the Targeted Temperature Management (TTM) trial were included. Results: In the pilot trial, plasma miR-122-5p at admission after OHCA was 400-fold elevated compared to controls. In the main trial, plasma miR-122-5p at admission was independently associated with lactate and bystander cardiopulmonary resuscitation. miR-122-5p at admission was not associated with shock at admission (p = 0.14) or all-cause mortality (p = 0.35). Target temperature (33 °C vs 36 °C) was not associated with miR-122-5p levels at any time point. Conclusions: After OHCA, miR-122-5p demonstrated a marked acute increase in plasma and was independently associated with lactate and bystander resuscitation. However, miR-122-5p at admission was not associated with all-cause mortality or shock at admission.

Objective: To compare the effects of extended- versus short-time noninvasive positive pressure ventilation on pulmonary function, tissue perfusion, and clinical outcomes in the early postoperative period following coronary artery bypass surgery in patients with preserved left ventricular function. Methods: Patients were randomized into two groups according to noninvasive positive pressure ventilation intensity: short-time noninvasive positive pressure ventilation n=20 (S-NPPV) and extended-time noninvasive positive pressure ventilation n=21 (E-NPPV). S-NPPV was applied for 60 minutes during immediate postoperative period and 10 minutes, twice daily, from postoperative days 1-5. E-NPPV was performed for at least six hours during immediate postoperative period and 60 minutes, twice daily, from postoperative days 1-5. As a primary outcome, tissue perfusion was determined by central venous oxygen saturation and blood lactate level measured after anesthetic induction, immediately after extubation and following noninvasive positive pressure ventilation protocols. As a secondary outcome, pulmonary function tests were performed preoperatively and in the postoperative days 1, 3, and 5; clinical outcomes were recorded. Results: Significant drop in blood lactate levels and an improvement in central venous oxygen saturation values in the E-NPPV group were observed when compared with S-NPPV group after study protocol (P

OBJECTIVE: The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far.METHODS: The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies.RESULTS: As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%).CONCLUSION: The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock.

Introduction: A growing number of dialysis patients is treated with home haemodialysis. Our current pre-analytical protocols require patients to centrifuge the blood sample and transfer the plasma into a new tube at home. This procedure is prone to errors and precludes accurate bicarbonate measurement, required for determining dialysate bicarbonate concentration and maintaining acid-base status. We therefore evaluated whether cooled overnight storage of gel separated plasma is an acceptable alternative. Materials and methods: Venous blood of 34 haemodialysis patients was collected in 2 lithium heparin blood collection tubes with gel separator (LH PSTTM II, REF 367374; Becton Dickinson, New Jersey, USA). One tube was analysed directly for measurement of bicarbonate, potassium, calcium, phosphate, glucose, urea, lactate, aspartate aminotransferase (AST), and lactate dehydrogenase (LD); whereas the other was centrifuged and stored unopened at 4 °C and analysed 24 h later. To measure analyte stability after 24 h of storage, the mean difference was calculated and compared to the total allowable error (TEa) which was used as acceptance limit. Results: Potassium (Z = - 4.28, P < 0.001), phosphate (Z = - 3.26, P = 0.001), lactate (Z = - 5.11, P < 0.001) and AST (Z = - 2.71, P = 0.007) concentrations were higher, whereas glucose (Z = 4.00, P < 0.001) and LD (Z = 3.13, P = 0.002) showed a reduction. All mean differences were smaller than the TEa and thus not clinically relevant. Bicarbonate (Z = 0.69, P = 0.491), calcium (Z = - 0.23, P = 0.815) and urea (Z = 0.81, P =0.415) concentrations were stable. Conclusions: Our less complex, user-friendly pre-analytical procedure resulted in at least 24 h stability of analytes relevant for monitoring haemodialysis, including bicarbonate. This allows shipment and analysis the next day.

AIM: We hypothesized that compromised cardiac output in asphyxiated infants may influence on the rate of disappearance of lactate due to insufficient perfusion.METHODS: The study was a prospective, observational study, where infants with perinatal asphyxia who met the criteria for therapeutic hypothermia were included. Cardiac output, stroke volume and heart rate were measured by electrical velocimetry in 15 newborn infants with perinatal asphyxia during the first six hours of active therapeutic hypothermia. Results from routine blood samples were collected retrospectively. Cardiac parameters were also measured in 10 healthy, term infants after caesarian section. Cardiac parameters were compared between the asphyxiated group and the control group prior to and during hypothermia. Rate of disappearance of lactate was correlated to cardiac output in the asphyxiated infants.RESULTS: Cardiac output was stable in the healthy infants from 0.5 to 6 hours postnatally. The infants with perinatal asphyxia had lower cardiac output prior to and during therapeutic hypothermia compared to the control group. Rate of disappearance of lactate was not related to cardiac output.CONCLUSION: An association between disappearance of lactate acidosis and low cardiac output was not confirmed. A low rate of disappearance of lactate may rather be an indicator of organ injury due to asphyxia.

Objective: Blood lactate concentration (L) and lactate kinetic (LK) over time might be a helpful marker of the shock severity. The purpose of this study is to analyze whether the L and LK could correlate with the outcome and the therapy of patients with different types of shock.Methods: Design: A 3.5-year retrospective observational study. Patients: Eighteen years of age or older, diagnosed with shock were included. Arterial L measurements were performed upon admission and approximatively 3 and 6 h later. The evolution of lactate over this period of time was correlated with the outcome and therapy. Interventions: Univariate and multivariable statistical tests were performed to examine the relation between the initial L/LK and the in-hospital mortality, total mortality, length of stay (LOS), the LOS at the intensive care unit and the administered therapy. The optimal cut-off point of the LK over time to predict the mortality was calculated.Results: The initial L and the 6 h LK were significantly associated with the outcome. The higher the initial L and lower the LK, the higher the risk of mortality in the hospital or within 6 months. Moreover, the higher the initial L and lower the 6 h LK, the longer was the LOS. A relation between the initial L/LK and the required therapy was found. The optimal cut-off for the 6-h LK is 38.1%. Patients with a 6 h LK >38.1% had a significantly higher chance of survival.Conclusions: A significant relationship between the L/6-h LK and the outcome and treatment was found. The optimal survival cut-off point of 6 h LK in our study was 38.1%.

Aims: \ud To assess potential causes of metformin intolerance, including altered metformin uptake from the intestine, increased anaerobic glucose utilization and subsequent lactate production, altered serotonin uptake, and altered bile acid pool.\ud \ud Methods: \ud For this pharmacokinetic study, we recruited 10 severely intolerant and 10 tolerant individuals, matched for age, sex and body mass index. A single 500‐mg dose of metformin was administered, with blood sampling at 12 time points over 24 hours. Blood samples were analysed for metformin, lactate, serotonin and bile acid concentrations, and compared across the phenotypes.\ud \ud Results: \ud The intolerant individuals were severely intolerant to 500 mg metformin. No significant difference was identified between tolerant and intolerant cohorts in metformin pharmacokinetics: median (interquartile range [IQR]) peak concentration 2.1 (1.7‐2.3) mg/L and 2.0 (1.8‐2.2) mg/L, respectively (P = .76); time to peak concentration 2.5 hours; median (IQR) area under the curve (AUC)0–24 16.9 (13.9‐18.6) and 13.9 (12.9‐16.8) mg/L*h, respectively (P = .72). Lactate concentration peaked at 3.5 hours, with mean peak concentration of 2.4 mmol/L in both cohorts (95% CI 2.0‐2.8 and 1.8‐3.0 mmol/L, respectively), and similar incremental AUC0–24 in each cohort: tolerant cohort 6.98 (95% CI 3.03‐10.93) and intolerant cohort 4.47 (95% CI –3.12‐12.06) mmol/L*h (P = .55). Neither serotonin nor bile acid concentrations were significantly different.\ud \ud Conclusions: \ud Despite evidence of severe intolerance in our cohort, there was no significant difference in metformin pharmacokinetics or systemic measures of lactate, serotonin or bile acids. This suggests that metformin intolerance may be attributable to local factors within the lumen or enterocyte.

Recreational soccer is an effective health-promoting activity, but it is unclear how different game formats influence internal and external load. Thus, to be able to advise how to maximise the outcome of recreational football, we examined movement pattern and physiological response in 11 untrained men (32.6 ± 6.7 yrs, 23.3 ± 4.9 fat%, 43.4 ± 5.3 ml·min -1·kg -1) during three football sessions comprising 4 × 12 min of 3v3, 5v5 or 7v7 with a constant pitch size of 20 × 40 m. Movement pattern, heart rate (HR), blood lactate and RPE were measured during and after the 12-min periods. Greater (P < 0.05) total distance and high-speed distance was covered during 3v3 than 5v5 (14 and 30%) and 7v7 (15 and 75%). Mean HR was higher in 3v3 (85.7 ± 5.7%HRmax) and 5v5 (84.2 ± 5.1%HRmax) than in 7v7 (80.7 ± 4.6%HRmax, P < 0.05) and percentage time >90%HR was higher in 3v3 (43 ± 18%, P < 0.05) than in 5v5 (28 ± 21%) and 7v7 (18 ± 14%). Blood lactate was higher in 3v3 (7.4 ± 2.7 mmol·l -1) than in 7v7 (4.5 ± 2.2 mmol·l -1, P < 0.001) but not in 5v5 (6.1 ± 2.1 mmol·l -1, P = 0.061). RPE was higher in 3v3 (6.7 ± 2.3, P < 0.01) than in 5v5 (5.2 ± 2.2) and 7v7 (4.3 ± 2.3). In conclusion, higher external and internal load was found with fewer players, when the pitch size is fixed.

OBJECTIVE: Upper gastrointestinal bleeding (UGIB) is a frequent medical emergency and several scoring systems are developed to help risk-stratify patients. We aimed to investigate if elevated arterial lactate (AL) was associated with 30-day mortality, need for hospital-based intervention, or rebleeding. Furthermore, we compared the performance of AL with existing scoring systems and examined if incorporation of AL could improve their predictive ability.MATERIALS AND METHODS: Retrospective cohort study of 331 consecutive patients admitted with UGIB during a one-year period. Multivariate analyses were performed to evaluate the association between AL and outcomes. Receiver operating characteristic curves were used to compare AL with existing scoring systems and to test if incorporation of AL could significantly increase their performance.RESULTS: AL was significantly associated with mortality (p = .001), need for hospital-based intervention (p = .005), and rebleeding (p = .031). In predicting mortality and rebleeding, AL performed equally to existing scoring systems, however, inferior to all, in predicting need for intervention. Two of the scoring systems were marginally improved in predicting mortality if AL was included.CONCLUSIONS: AL is associated with adverse outcomes in patients with UGIB, but has only similar or inferior ability to predict relevant clinical outcomes compared to existing scoring systems. Although AL could enhance performance of two scorings systems in predicting mortality, it does not have an apparent clinical significance. Thus, our data does not support routine measurement of AL in patients with UGIB.

It was investigated whether a newly developed discipline-specific test for elite-level trapeze sailors is reliable and sensitive. Furthermore, the physical demands of trapeze sailing were examined. In part 1, 9 national team athletes were accustomed to a simulated sailing test, which subsequently was completed on 4 occasions to determine test reliability and sensitivity to manipulations in body weight. Rope-pulling mean power output (MPO), oxygen consumption (VO2), heart rate (HR), and blood lactate values were acquired in all trials. In part 2, 6 sailors completed on-water racing with concurrent measurements of VO2, HR, and blood lactate. VO2max was determined during an incremental treadmill running test. Typical error, minimal difference, and ICC for average MPO in the test were 1.3%, 1.7%, and 0.99%, respectively. Adding 4 kg of external body weight caused a decrease in average MPO (270 ± 45W vs 265 ± 45W, P 2 (2.44 ± 0.23 L·min−1 vs 2.55 ± 0.26 L·min−1, P 2, HR, and blood lactate during on-water sailing were 54.5% ± 7.2% VO2max, 75.1% ± 3.1% HRmax, and 5.8 ± 2.7 mmol·L−1, respectively. However, VO2 and HR were substantially higher for periods of the race as peak values were 83.5% ± 11.4% and 89.9% ± 1.7% of max, respectively. In conclusion, the present test is reliable and sensitive, thus providing a sailing-specific alternative to traditional physical testing of elite trapeze sailors. Additionally, on-water racing requires moderate aerobic energy production, although oxygen consumption can approach maximal levels for short periods of time.

Glucose-fructose ingestion increases glucose and lactate oxidation during exercise. We hypothesized that training with glucose-fructose would induce key adaptations in lactate metabolism. Two groups of eight sedentary males were endurance-trained for three weeks while ingesting either glucose-fructose (GF) or water (C). Effects of glucose-fructose on lactate appearance, oxidation, and clearance were measured at rest and during exercise, pre-training, and post-training. Pre-training, resting lactate appearance was 3.6 ± 0.5 vs. 3.6 ± 0.4 mg·kg javax.xml.bind.JAXBElement@1ca983d4 ·min javax.xml.bind.JAXBElement@7b9c8542 in GF and C, and was increased to 11.2 ± 1.4 vs. 8.8 ± 0.7 mg·kg javax.xml.bind.JAXBElement@1db23ebc ·min javax.xml.bind.JAXBElement@7d82d9ab by exercise (Exercise: javax.xml.bind.JAXBElement@2d6552ec < 0.01). Lactate oxidation represented 20.6% ± 1.0% and 17.5% ± 1.7% of lactate appearance at rest, and 86.3% ± 3.8% and 86.8% ± 6.6% during exercise (Exercise: javax.xml.bind.JAXBElement@324c6497 < 0.01) in GF and C, respectively. Training with GF increased resting lactate appearance and oxidation (Training × Intervention: both javax.xml.bind.JAXBElement@3e07fbbc < 0.05), but not during exercise (Training × Intervention: both javax.xml.bind.JAXBElement@55a33256 > 0.05). Training with GF and C had similar effects to increase lactate clearance during exercise (+15.5 ± 9.2 and +10.1 ± 5.9 mL·kg javax.xml.bind.JAXBElement@52d6e83c ·min javax.xml.bind.JAXBElement@3ef562d ; Training: javax.xml.bind.JAXBElement@23497f7 < 0.01; Training × Intervention: javax.xml.bind.JAXBElement@4ec92465 = 0.97). The findings of this study show that in sedentary participants, glucose-fructose ingestion leads to high systemic lactate appearance, most of which is disposed non-oxidatively at rest and is oxidized during exercise. Training with or without glucose-fructose increases lactate clearance, without altering lactate appearance and oxidation during exercise.

Purpose Understanding the underlying cause of mortality in sepsis has broad implications for both clinical care and interventional trial design. However, reasons for death in sepsis remain poorly understood. We sought to characterize reasons for in-hospital mortality in a population of patients with sepsis or septic shock. Materials and methods We performed a retrospective review of patients admitted to the intensive care unit with sepsis or septic shock who died during their index admission. Reasons for death were classified into 6 categories determined a priori by group consensus. Interrater reliability was calculated and Fleiss κ reported. The associations between selected patient characteristics (eg, serum lactate) and reason for death were also assessed. Results One hundred fifteen patients were included. Refractory shock (40%) and comorbid withdrawal of care (44%) were the most common reasons for death. Overall interrater agreement was substantial (κ = 0.61, P

OBJECTIVE Addition of fructose to the diet of normal weight and overweight subjects can increase postprandial plasma triglyceride and uric acid concentration. We, therefore, assessed whether replacing sugar-sweetened beverages (SSB) with artificially-sweetened beverages (ASB) in the diet of overweight and obese subjects would decrease these parameters. METHODS Twenty-six participants of the REDUCS study, which assessed the effects of replacing SSB by ASB over 12 weeks on intra-hepatocellular lipid concentration, were included in this sub-analysis. All were studied after a four-week run-in period during which they consumed their usual diet and SSBs, and after a 12-week intervention in which they were randomly assigned to replace their SSBs with ASBs (ASB arm) or to continue their usual diet and SSBs (control arm, CTRL). At the end of run-in (week 4) and again at the end of intervention (week 16), they took part in an 8.5 h metabolic investigation during which their plasma glucose, insulin, glucagon, lactate, triglyceride (TG), non-esterified fatty acids (NEFA), and uric acid concentrations were measured over a 30 min fasting period (-30-0 min), then every 2 h over 480 min. with ingestion of standard breakfast at time 0 min and a standard lunch at time 240 min. Breakfast and lunch were consumed together with a 3.3 dL SSB at week 4 and with either an ASB (ASB arm) or a SSB (CTRL arm) at week 16. After analyzing the whole group, a secondary analysis was performed on 14 subjects with hepatic steatosis (seven randomized to ASB, seven to CTRL) and 12 subjects without hepatic steatosis (six randomized to ASB and six to CTRL). RESULTS Ingestion of meals increased plasma glucose, insulin, glucagon, lactate, and TG concentrations and decreased NEFA concentrations, but with no significant difference of integrated postprandial responses between week 4 and week 16 in both ASB and CTRL, except for a slightly decreased glucagon response in ASB. There was, however, no significant postprandial increase in uric acid concentration in both arms. In the secondary analysis, replacing SSBs with ASBs did not significantly change postprandial TG and uric acid concentrations irrespective of the presence or not of hepatic steatosis, Conclusions: In overweight, high SSB consumers, replacing SSBs with ASBs during 12 weeks did not significantly alter post-prandial TG and uric acid concentration, in spite of the lower energy and fructose content of the meals. These effects were globally the same in subjects without and with hepatic steatosis.

A 9-year-old boy with McArdle disease, who demonstrated remarkable recovery of objectively measured exercise tolerance after 1 year of follow-up, during which he pursued age-appropriate physical activities. The patient presented 1 year previously with severe myalgia, muscle weakness, proteinuria, hematuria, hyperthermia, and elevated creatine kinase levels after noncompetitive swimming. At that time, he reported a 3-year history of general myalgia and poor exercise tolerance. He was diagnosed with McArdle disease by both biochemical and genetic methods. Subsequently he performed a maximal exercise test and was prescribed a return to age-appropriate physical activity (protected by a pre-exercise dietary consumption of approximately 20 g carbohydrate). At 1-year follow up, he reported no subsequent acute clinical episodes, no general problems with exercise either at school or in ordinary activities, a virtual normalization of serum creatine kinase levels, and a 14% increase in body mass-adjusted peak oxygen uptake (from 18.8 to 21.8 mL O2/kg/min). The results suggest that, with protection by increasing pre-exercise blood glucose with carbohydrate ingestion, a substantially normal lifestyle may be possible in some children with McArdle disease. 1.505 JCR (2008) Q2, 38/86 Pediatrics; Q3, 102/156 Clinical neurology UEM

Elevated pancreatic β-cell cholesterol levels impair insulin secretion and reduce plasma insulin levels. This study establishes that low plasma insulin levels have a detrimental effect on two major insulin target tissues: adipose tissue and skeletal muscle. Mice with increased β-cell cholesterol levels were generated by conditional deletion of the ATP-binding cassette transporters, ABCA1 and ABCG1, in β-cells (β-DKO mice). Insulin secretion was impaired in these mice under basal and high-glucose conditions, and glucose disposal was shifted from skeletal muscle to adipose tissue. The β-DKO mice also had increased body fat and adipose tissue macrophage content, elevated plasma interleukin-6 and MCP-1 levels, and decreased skeletal muscle mass. They were not, however, insulin resistant. The adipose tissue expansion and reduced skeletal muscle mass, but not the systemic inflammation or increased adipose tissue macrophage content, were reversed when plasma insulin levels were normalized by insulin supplementation. These studies identify a mechanism by which perturbation of β-cell cholesterol homeostasis and impaired insulin secretion increase adiposity, reduce skeletal muscle mass, and cause systemic inflammation. They further identify β-cell dysfunction as a potential therapeutic target in people at increased risk of developing type 2 diabetes.

Background: Sodium bicarbonate intake has been shown to improve exercise tolerance, but the effects on high-intensity intermittent exercise are less clear. Thus, the aim of the present study was to determine the effect of sodium bicarbonate intake on Yo-Yo intermittent recovery level 2 test performance in trained young men. Methods: Thirteen men aged 23 ± 1 year (height: 180 ± 2 cm, weight: 78 ± 3 kg; VO2max: 61.3 ± 3.3 mlO2 · kg−1 · min−1; means ± SEM) performed the Yo-Yo intermittent recovery level 2 test (Yo-Yo IR2) on two separate occasions in randomized order with (SBC) and without (CON) prior intake of sodium bicarbonate (0.4 g · kg−1 body weight). Heart rate and rating of perceived exertion (RPE) were measured during the test and venous blood samples were taken frequently. Results: Yo-Yo IR2 performance was 14 % higher (P = 0.04) in SBC than in CON (735 ± 61 vs 646 ± 46 m, respectively). Blood pH and bicarbonate were similar between trials at baseline, but higher (P = 0.003) immediately prior to the Yo-Yo IR2 test in SBC than in CON (7.44 ± 0.01 vs 7.32 ± 0.01 and 33.7 ± 3.2 vs 27.3 ± 0.6 mmol · l−1, respectively). Blood lactate was 0.9 ± 0.1 and 0.8 ± 0.1 mmol · l−1 at baseline and increased to 11.3 ± 1.4 and 9.4 ± 0.8 mmol · l−1 at exhaustion in SBC and CON, respectively, being higher (P = 0.03) in SBC. Additionally, peak blood lactate was higher (P = 0.02) in SBC than in CON (11.7 ± 1.2 vs 10.2 ± 0.7 mmol · l−1). Blood glucose, plasma K+ and Na+ were not different between trials. Peak heart rate reached at exhaustion was 197 ± 3 and 195 ± 3 bpm in SBC and CON, respectively, with no difference between conditions. RPE was 7 % lower (P = 0.003) in SBC than in CON after 440 m, but similar at exhaustion (19.3 ± 0.2 and 19.5 ± 0.2). Conclusion: In conclusion, high-intensity intermittent exercise performance is improved by prior intake of sodium bicarbonate in trained young men, with concomitant elevations in blood alkalosis and peak blood lactate levels, as well as lowered rating of perceived exertion.

We tested whether the kinetics of systemic O2 delivery (Q̇aO2) at exercise start was faster than that of lung O2 uptake (V̇o2), being dictated by that of cardiac output (Q̇), and whether changes in Q̇ would explain the postulated rapid phase of the V̇o2 increase. Simultaneous determinations of beat-by-beat (BBB) Q̇ and Q̇aO2, and breath-by-breath V̇o2 at the onset of constant load exercises at 50 and 100 W were obtained on six men (age 24.2 ± 3.2 years, maximal aerobic power 333 ± 61 W). V̇o2 was determined using Grønlund's algorithm. Q̇ was computed from BBB stroke volume (Qst, from arterial pulse pressure profiles) and heart rate ( fh, electrocardiograpy) and calibrated against a steady-state method. This, along with the time course of hemoglobin concentration and arterial O2 saturation (infrared oximetry) allowed computation of BBB Q̇aO2. The Q̇, Q̇aO2 and V̇o2 kinetics were analyzed with single and double exponential models. fh, Qst, Q̇, and V̇o2 increased upon exercise onset to reach a new steady state. The kinetics of Q̇aO2 had the same time constants as that of Q̇. The latter was twofold faster than that of V̇o2. The V̇o2 kinetics were faster than previously reported for muscle phosphocreatine decrease. Within a two-phase model, because of the Fick equation, the amplitude of phase I Q̇ changes fully explained the phase I of V̇o2 increase. We suggest that in unsteady states, lung V̇o2 is dissociated from muscle O2 consumption. The two components of Q̇ and Q̇aO2 kinetics may reflect vagal withdrawal and sympathetic activation.

The purpose of this study was to investigate the effect of "with goalkeeper" (SSGwith) and "without goalkeeper" (SSGwithout) conditions on players' physiological responses and time-motion characteristics in small-sided games. Sixteen young soccer players (age: 16.5 ± 1.5 years; height: 175.5 ± 5.2 cm; body mass: 63.0 ± 6.9 kg; training experience: 6.3 ± 1.3 years) participated in 2 different 2-a-side, 3-a-side, and 4-a-side games: SSGwith and SSGwithout. The players underwent anthropometric measurements (height and body mass) followed by the Yo-Yo intermittent recovery test (level 1). Then they played 2-a-side, 3-a-side, and 4-a-side SSGwith and SSGwithout soccer-specific SSGs in random order at 2-day intervals. Heart rate (HR) responses and distance covered in different speed zones (walking [WLK, 0-6.9 km·h(-1)], low-intensity running [LIR, 7.0-12.9 km·h(-1)], moderate-intensity running [MIR, 13.0-17.9 km·h(-1)], and high-intensity running [HIR, >18 km·h(-1)]) were measured during the SSGs, whereas the rating of perceived exertion (RPE) and blood lactate (La) were determined at the end of the last bout of each SSG. During the SSGwithout players showed higher %HR, La, and RPE (p ≤ 0.05), greater distance covered in LIR, MIR, HIR, and total distance (p ≤ 0.05) compared with the SSGwith during the 2-a-side, 3-a-side, and 4-a-side games. The results of this study suggest that both SSGwith and SSGwithout could be used for the physiological adaptations required for soccer-specific aerobic endurance. However, if coaches want both higher physiological responses and greater distance covered in the intensity running zone from their teams, SSGwithout should be organized. In addition, this study also suggests that smaller format games (i.e., 2-a-side) may promote some anaerobic adaptations for youth soccer players.

To compare the hepatosplanchnic oxygen consumption (VO2) with the hepatic and splanchnic VO2 and to calculate the critical oxygen delivery (DO2crit) below which VO2 decreases in the hepatic, splanchnic, and hepatosplanchnic regions in a model of hypoxemic hypoxia.Prospective animal study.University research laboratory.Anesthetized and ventilated pigs (n = 7).The right carotid artery was cannulated to measure mean arterial pressure. A pulmonary artery catheter was inserted to measure mean pulmonary arterial pressure and cardiac output. After a midline abdominal incision, two flow probes were positioned around the portal vein and the hepatic artery to measure portal vein blood flow and hepatic artery blood flow. Oxygen and lactate contents in the carotid artery, the portal vein, and the hepatic vein were measured in blood samples obtained from the appropriate catheters.After a 2-hr stabilization period, hemodynamic and biological variables were recorded during acute hypoxemic hypoxia (FIO2 = 0.5, 0.4, 0.3, 0.21, 0.15, 0.10, and 0.07). VO2, DO2, and DO2crit were determined in the hepatic, splanchnic, and hepatosplanchnic regions. The hepatosplanchnic VO2 was 48 +/- 5 mL/min at high FIO2 (40% for the liver and 60% for the splanchnic organs) and decreased below FIO2 of 0.15. Lactate uptake in the whole hepatosplanchnic region remained steady at FIO2 values of 0.5 to 0.15 and then switched to a lactate release at low FIO2. However, the splanchnic region released lactate, whereas lactate was taken up by the liver. DO2crit in the hepatic, splanchnic, and hepatosplanchnic regions was 24 +/- 3, 38 +/- 2, and 49 +/- 4 mL/min, but the systemic DO2crit, below which regional VO2 became oxygen supply dependent, did not differ in the liver, splanchnic, and hepatosplanchnic regions.The variables of oxygenation and lactate flux measured in the hepatosplanchnic region summarize the metabolic changes of various organs that may vary in different ways during hypoxemic hypoxia.

Purpose: The aim of the present study was to investigate the influence of muscle glycogen content on sarcoplasmic reticulum (SR) function and peak power output (Wpeak) in elite endurance athletes. Methods: Fourteen highly trained male triathletes (V̇O2max = 66.5 ± 1.3 mL O2·kg·min), performed 4 h of glycogen-depleting cycling exercise (HRmean = 73% ± 1% of maximum). During the first 4 h of recovery, athletes received either water (H2O) or carbohydrate (CHO), separating alterations in muscle glycogen content from acute changes affecting SR function and performance. Thereafter, all subjects received CHO-enriched food for the remaining 20-h recovery period. Results: Immediately after exercise, muscle glycogen content and SR Ca release rate was reduced to 32% ± 4% (225 ± 28 mmol·kg dw) and 86% ± 2% of initial levels, respectively (P < 0.01). Glycogen markedly recovered after 4 h of recovery with CHO (61% ± 2% of preexercise) and SR Ca release rate returned to preexercise level. However, in the absence of CHO during the first 4 h of recovery, glycogen and SR Ca release rate remained depressed, with the normalization of both parameters at the end of the 24 h of recovery after receiving a CHO-enriched diet. Linear regression demonstrated a significant correlation between SR Ca release rate and muscle glycogen content (P < 0.01, r = 0.30). The 4 h of cycling exercise reduced Wpeak by 5.5%-8.9% at different cadences (P < 0.05), and Wpeak was normalized after 4 h of recovery with CHO, whereas Wpeak remained depressed (P < 0.05) after water provision. Wpeak was fully recovered after 24 h in both the H2O and the CHO group. Conclusion: In conclusion, the present results suggest that low muscle glycogen depresses muscle SR Ca release rate, which may contribute to fatigue and delayed recovery of Wpeak 4 h postexercise. © 2014 by the American College of Sports Medicine. Language of Original Document: English

BACKGROUND: This study aimed to explore the effects of progressive resistance exercise training (PRET) on hemorheology. MATERIAL/METHODS: Exercise sessions included 1-3 sets of 8-12 repetitions at 40-60% of 1-repetition maximum (1-RM) for 3 weeks and at 75-80% of 1-RM during weeks 4-12. Red blood cell (RBC) deformability and aggregation were determined by ektacytometry, plasma and whole blood viscosities (WBV) by rotational viscometry. Lactate concentration was evaluated by an analyzer and fibrinogen was evaluated by coagulometry. Plasma total oxidant/antioxidant status was measured by colorimetry. RESULTS: Following an acute increase after exercise on the first day, RBC deformability was elevated during weeks 3 and 4 (p=0.028; p=0.034, respectively). The last exercise protocol applied in week 12 again caused an acute increase in this parameter (p=0.034). RBC aggregation was increased acutely on the first day, but decreased after that throughout the protocol (p

BACKGROUND: Plasma and urinary levels of D-lactate have been linked to the presence of diabetes. Previously developed techniques have shown several limitations to further evaluate D-lactate as a biomarker for this condition. METHODS: D- and L-lactate were quantified using ultraperformance liquid chromatography tandem mass spectrometry with labelled internal standard. Samples were derivatized with diacetyl-L-tartaric anhydride and separated on a C(18)-reversed phase column. D- and L-lactate were analysed in plasma and urine of controls, patients with inflammatory bowel disease (IBD), and patients with type 2 diabetes (T2DM). RESULTS: Quantitative analysis of D- and L-lactate was achieved successfully. Calibration curves were linear (r(2) > 0.99) over the physiological and pathophysiological ranges. Recoveries for urine and plasma were between 96% and 113%. Inter- and intra-assay variations were between 2% and 9%. The limits of detection of D-lactate and L-lactate in plasma were 0.7 μmol/L and 0.2 μmol/L, respectively. The limits of detection of D-lactate and L-lactate in urine were 8.1 nmol/mmol creatinine and 4.4 nmol/mmol creatinine, respectively. Plasma and urinary levels of D- and L-lactate were increased in patients with IBD and T2DM as compared with controls. CONCLUSION: The presented method proved to be suitable for the quantification of D- and L-lactate and opens the possibility to explore the use of D-lactate as a biomarker.

BACKGROUND: Plasma and urinary levels of D-lactate have been linked to the presence of diabetes. Previously developed techniques have shown several limitations to further evaluate D-lactate as a biomarker for this condition. METHODS: D- and L-lactate were quantified using ultraperformance liquid chromatography tandem mass spectrometry with labelled internal standard. Samples were derivatized with diacetyl-L-tartaric anhydride and separated on a C(18)-reversed phase column. D- and L-lactate were analysed in plasma and urine of controls, patients with inflammatory bowel disease (IBD), and patients with type 2 diabetes (T2DM). RESULTS: Quantitative analysis of D- and L-lactate was achieved successfully. Calibration curves were linear (r(2) > 0.99) over the physiological and pathophysiological ranges. Recoveries for urine and plasma were between 96% and 113%. Inter- and intra-assay variations were between 2% and 9%. The limits of detection of D-lactate and L-lactate in plasma were 0.7 μmol/L and 0.2 μmol/L, respectively. The limits of detection of D-lactate and L-lactate in urine were 8.1 nmol/mmol creatinine and 4.4 nmol/mmol creatinine, respectively. Plasma and urinary levels of D- and L-lactate were increased in patients with IBD and T2DM as compared with controls. CONCLUSION: The presented method proved to be suitable for the quantification of D- and L-lactate and opens the possibility to explore the use of D-lactate as a biomarker.

The purpose of this study was to examine the influence of different team formation methods on the physiological responses to and time-motion characteristics of 4-a-side small-sided games (SSG4) in young soccer players. Thirty-two young soccer players (age 16.2 ± 0.7 years; height 172.9 ± 6.1 cm; body mass 64.1 ± 7.7 kg) voluntarily participated in this study. Anthropometric measurements, technical tests, and maximum oxygen uptake (V[Combining Dot Above]O2max) tests were carried out on the players. The SSG4 teams were then created using 4 different methods: according to the coaches' subjective evaluation (CE), technical scores (TS), V[Combining Dot Above]O2max (AP), and V[Combining Dot Above]O2max multiplied by TSs (CG). The teams thus created played 4 bouts of SSG4 at 2-day intervals. During the SSG4, heart rate (HR) responses, distance covered, and time spent in HRmax zones were recorded. In addition, rating of perceived exertion (RPE) and blood lactate level (La) were determined at the end of the last bout of each SSG4. Percent of HRmax (%HRmax), La, and RPE responses during SSG4 were significantly higher for teams chosen according to AP and CG compared with that according to CE and TS (p < 0.05). In addition, teams chosen by AP and CG spent significantly more time in zone 4 (>90% HRmax ) and covered a greater distance in the high-intensity running zone (>18 km·h) than did teams formed according to TS. Moreover, AP teams covered significantly greater total distance than TS teams did (p < 0.05). In conclusion, to spend more time in both the high-intensity HR zone and the high-intensity running zone, the teams in SSG4 should be formed according to the players' V[Combining Dot Above]O2max values or the values calculated using both the V[Combining Dot Above]O2max and technique scores.

The purpose of this study was to compare the blood lactate (La-), heart rate (HR) and percentage of maximum HR (%HRmax) responses among the small-sided games (SSGs) in elite young soccer players. Sixteen players (average age 15.7 6 0.4 years; height 176.8 6 4.6 cm; body mass 65.5 6 5.6 kg; VO2max 53.1 6 5.9 ml · kg(-1) · min(-1); HRmax 195.9 6 7.4 b · min(-1)) volunteered to perform the YoYo intermittent recovery test and 6 bouts of soccer drills including 1-a-side, 2-a-side, 3-a-side, and 4-a-side games without a goalkeeper in random order at 2-day intervals. The differences in La-, HR and%HRmax either among the SSGs or among the bouts were identified using 4 x 6 (games x exercise bouts) 2-way analysis of variance with repeated measures. Significant differences were found on La-, HR, and %HRmax among the bouts (p ≤ 0.05). The 3-a-side and 4-a-side games were significantly higher than 1-a-side and 2-a-side games on HR and %HRmax (p ≤ 0.05), whereas the 1-a-side game significantly resulted in higher La- responses compared to other SSGs. This study demonstrated that physiological responses during the 1-a-side and 2-a-side games were different compared to 3-a-side and 4-a-side games. Therefore, it can be concluded that a decreased number of players results in increased intensity during SSGs including 6 bouts. These results suggest that coaches should pay attention on choosing the SSG type and the number of bouts to improve desired physical conditioning of elite young soccer players in soccer training.

Made available in DSpace on 2022-04-29T07:13:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-01 Objective: Total sleep or selective REM-sleep deprivation (SD) increases aggressiveness. Rats that display fighting when submitted to sleep-deprivation are those that manifest wild running (WR), a panic-like flight that precedes tonic-clonic seizures induced by intense acoustic stimulation (audiogenic epilepsy). The incidence of WR-sensitive rats in the colonies around the world may reach 20%, which makes important to know the other characteristics of these animals for both sleep and other kinds of experimental research. Based on the report of their reduced body weight, we investigated some glucose metabolism parameters. Methods: Adult male Wistar rats were submitted to high-intensity acoustic stimulation (112dB, 60s) and then classified as WR-sensitive or WR-resistant rats. Glycemia and insulinemia, measured by glucometer and radioimmunoassay, respectively, and body weight were analyzed during three months. At the end of this period, intraperitoneal glucose and insulin tolerance tests were performed, and hepatic fat and glycogen content were also determined. Results: WR-sensitive rats showed proportionally less gain of body mass compared to the resistant ones (p

The aim of this study was to investigate the synergistic effects of endurance training and hypoxia on endurance performance in normoxic and hypoxic conditions (approximately 3000 m above sea level) as well as on lactate and glucose metabolism during prolonged exercise. For this purpose, 14 well-trained cyclists performed 12 training sessions in conditions of normobaric hypoxia (HYP group, n = 7) or normoxia (NOR group, n = 7) over 4 weeks. Before and after training, lactate and glucose turnover rates were measured by infusion of exogenous lactate and stable isotope tracers. Endurance performance was assessed during incremental tests performed in normoxia and hypoxia and a 40 km time trial performed in normoxia. After training, performance was similarly and significantly improved in the NOR and HYP groups (training, P < 0.001) in normoxic conditions. No further effect of hypoxic training was found on markers of endurance performance in hypoxia (training x hypoxia interaction, n.s.). In addition, training and hypoxia had no significant effect on lactate turnover rate. In contrast, there was a significant interaction of training and hypoxia (P < 0.05) on glucose metabolism, as follows: plasma insulin and glucose concentrations were significantly increased; glucose metabolic clearance rate was decreased; and the insulin to glucagon ratio was increased after training in the HYP group. In conclusion, our results show that, compared with training in normoxia, training in hypoxia has no further effect on endurance performance in both normoxic and hypoxic conditions or on lactate metabolic clearance rate. Additionally, these findings suggest that training in hypoxia impairs blood glucose regulation in endurance-trained subjects during exercise.

Anterior cruciate ligament (ACL) reconstruction reestablishes electromyographic activity during moderate activities such as walking but is unclear if this is also the case in sports activities such as high intensity running that results in accumulation of metabolic fatigue. Nine bone-patella tendon-bone ACL reconstructed athletes were evaluated 19.2 (5.7) months post-operatively using a telemetric electromyographic system. The neuromuscular response of vastus lateralis and biceps femoris muscles was tested bilaterally on separate occasions during 10 min running at moderate intensity (20% below the lactate threshold) and 10 min running at high intensity (40% above the lactate threshold). During moderate intensity running, electromyographic activity did not change for either leg. During high intensity running, electromyographic activity did not change for the vastus lateralis of the ACL reconstructed leg [267.8 (142.8)-263.8 (128.9) microV, P > 0.05] while it increased significantly [294.2 (120.6)-317.1 (140.5) microV, P = 0.03] for the vastus lateralis of the intact leg. High intensity exercise that is associated with accumulation of metabolic fatigue, results in an impaired neuromuscular response for the vastus lateralis muscle of the ACL reconstructed leg. Knee Surg Sports Traumatol Arthrosc

Femoral arterial lines are used for continuous monitoring of arterial blood pressure in experimental studies. However, placement of a catheter in the femoral artery could produce acute limb ischemia with associated systemic effects. The aim of this study was to investigate the effect of femoral arterial line insertion on liver function, in a rabbit liver lobar ischemia-reperfusion (I/R) model. Four groups of animals (n = 6 each) were studied: groups 1 and 2 (sham) underwent laparotomy but no liver ischemia. In groups 3 and 4 (I/R), liver lobar ischemia was induced for 60 minutes followed by 7 hours of reperfusion. In groups 1 and 3, the arterial line was placed in the femoral artery whereas in groups 2 and 4 in the ear artery. Liver function was assessed by serum alanine aminotransferase (ALT) activity, bile flow, plasma lactate levels, and histology. Results are expressed as mean ± SEM. Alanine aminotransferase activity and lactate levels were significantly higher in the I/R femoral line group compared with the I/R ear line group at 7 hours postreperfusion. Bile production was significantly lower (75 ± 9.6 vs 112 ± 10 μL/min per 100 g liver weight). Histopathology showed more extensive hepatocellular necrosis and neutrophil accumulation in the I/R femoral line group compared with I/R ear line group. The sham femoral group showed liver injury, which was more marked than the ear line group (all P < .05). In conclusion, femoral artery cannulation induces remote liver injury. The use of femoral arterial lines should be avoided in experimental studies concerning liver function.

Clinically and experimentally male fetuses are at significantly greater risk of dying or suffering injury at birth, particularly after premature delivery. We undertook a retrospective cohort analysis of 60 female and 65 male singleton preterm fetal sheep (103–104 days, 0.7 gestation) with mean arterial blood pressure (MAP), heart rate, and carotid and femoral blood flow recordings during 25 min of umbilical cord occlusion in utero. Occlusions were stopped early if fetal MAP fell below 8 mmHg or if there was asystole for >20 s. Fetuses that were able to complete the full 25-min period of occlusion showed no differences between sexes for any cardiovascular responses. Similar numbers of occlusions were stopped early in males (mean: 21 min, n = 16) and females (mean: 23 min, n = 16); however, they showed different responses. Short-occlusion males ( n = 16) showed a slower initial fall in femoral vascular conductance, followed by greater bradycardia, hypotension, and associated organ hypoperfusion compared with full-occlusion fetuses. In contrast, short-occlusion females ( n = 16) showed a significantly more rapid early increase in femoral vascular conductance than the full-occlusion fetuses, followed by worsening of bradycardia and hypotension that was intermediate to the full-occlusion fetuses and short-occlusion males. Among all fetuses, MAP at 15 min of occlusion, corresponding with the time of the maximal rate of fall, was correlated with postmortem weight in males ( R2= 0.07) but not females. In conclusion, male and female fetuses showed remarkably similar chemoreflex and hemodynamic responses to severe asphyxia, but some males did show impaired hemodynamic adaptation within the normal weight range.

Recurrent episodes of confusion are most commonly due to transient brain dysfunction related to vascular, epileptic or metabolic abnormalities. We report here a 54-year-old patient who, in the months following an extensive surgery of the small intestine, developed several acute confusional episodes characterized by encephalopathic signs (such as behavioral changes, desorientation and somnolence), ataxia, nystagmus and dysarthria. A number of metabolic changes were demonstrated during the episodes, including metabolic acidosis with increased anion gap and an elevated blood level of D-lactate. Symptoms disappeared after treatment with antibiotics. D-lactate encephalopathy is a rare cause of recurrent confusion which could be suspected based on a characteristic association of clinical signs. Diagnosis is confirmed by appropriate dosages. We discussed the possible mechanisms leading to confusional episodes.