Metabolic and thermodynamic responses to dehydration-induced reductions in muscle blood flow in exercising humans

[EN] 1. The present study examined whether reductions in muscle blood flow with exercise-induced dehydration would reduce substrate delivery and metabolite and heat removal to and from active skeletal muscles during prolonged exercise in the heat. A second aim was to examine the effects of dehydration on fuel utilisation across the exercising leg and identify factors related to fatigue. 2. Seven cyclists performed two cycle ergometer exercise trials in the heat (35 C; 61 +/- 2 % of maximal oxygen consumption rate, VO2,max), separated by 1 week. During the first trial (dehydration, DE), they cycled until volitional exhaustion (135 +/- 4 min, mean +/- s.e.m.), while developing progressive DE and hyperthermia (3.9 +/- 0.3 % body weight loss and 39.7 +/- 0.2 C oesophageal temperature, Toes). On the second trial (control), they cycled for the same period of time maintaining euhydration by ingesting fluids and stabilising Toes at 38.2 +/- 0.1 degrees C. 3. After 20 min of exercise in both trials, leg blood flow (LBF) and leg exchange of lactate, glucose, free fatty acids (FFA) and glycerol were similar. During the 20 to 135 +/- 4 min period of exercise, LBF declined significantly in DE but tended to increase in control. Therefore, after 120 and 135 +/- 4 min of DE, LBF was 0.6 +/- 0.2 and 1.0 +/- 0.3 l min-1 lower (P < 0.05), respectively, compared with control. 4. The lower LBF after 2 h in DE did not alter glucose or FFA delivery compared with control. However, DE resulted in lower (P < 0.05) net FFA uptake and higher (P < 0.05) muscle glycogen utilisation (45 %), muscle lactate accumulation (4.6-fold) and net lactate release (52 %), without altering net glycerol release or net glucose uptake. 5. In both trials, the mean convective heat transfer from the exercising legs to the body core ranged from 6.3 +/- 1.7 to 7.2 +/- 1.3 kJ min-1, thereby accounting for 35-40 % of the estimated rate of heat production ( approximately 18 kJ min-1). 6. At exhaustion in DE, blood lactate values were low whereas blood glucose and muscle glycogen levels were still high. Exhaustion coincided with high body temperature ( approximately 40 C). 7. In conclusion, the present results demonstrate that reductions in exercising muscle blood flow with dehydration do not impair either the delivery of glucose and FFA or the removal of lactate during moderately intense prolonged exercise in the heat. However, dehydration during exercise in the heat elevates carbohydrate oxidation and lactate production. A major finding is that more than one-half of the metabolic heat liberated in the contracting leg muscles is dissipated directly to the surrounding environment. The present results indicate that hyperthermia, rather than altered metabolism, is the main factor underlying the early fatigue with dehydration during prolonged exercise in the heat.

Effects of dietary supplementation with synthetic vitamin D-3 and 25-hydroxycholecalciferol on blood calcium and phosphate levels and performance in laying hens

We investigated the effects of different dietary vitamin D regimen on selected blood parameters in laying hens. Supplementation with vitamin D-3 only was compared with a combination of vitamin D-3 and its metabolite 25-hydroxy-cholecalciferol (25(OH)D-3). Blood concentrations of total calcium, phosphate and 25 (OH)D-3 were determined. Four thousand one-day-old LSL chicks were split in two treatment groups and distributed to eight pens. The control group was given a commercial animal diet containing 2800 IU synthetic vitamin D-3 in the starter feed and 2000 IU synthetic vitamin D-3 in the pullet feed. The experimental group was fed the same commercial diet in which half the synthetic vitamin D-3 content had been substituted with 25(OH)D-3 (Hy center dot D (R)). At 18 weeks of age, pullets were transferred to the layer house. At the ages of 11, 18 and 34 weeks, between 120 and 160 blood samples were collected from both the control and the experimental groups, respectively. The experimental group had higher levels of 25 (OH)D-3 than the control group at all three ages. Serum calcium levels did not differ between the treatment groups at any age. With the onset of laying, calcium levels rose significantly. Whereas blood serum concentration at 18 weeks was 3 mmol/L in both treatment groups, it increased to 8.32 mmol/L in the control group and to 8.66 mmol/L in the experimental group at week 34. At weeks 11 and 34, phosphate was significantly lower in the experimental group. In conclusion, HyD (R) significantly affected serum phosphate and 25(OH)D-3 levels. No effects of (25(OH)D-3 supplementation on performance, shell quality and fractures of keelbones were found.

Membrane microdialysis: Evaluation of a new method to assess splanchnic tissue metabolism

OBJECTIVE: Measuring peritoneal lactate concentrations could be useful for detecting splanchnic hypoperfusion. The aims of this study were to evaluate the properties of a new membrane-based microdialyzer in vitro and to assess the ability of the dialyzer to detect a clinically relevant decrease in splanchnic blood flow in vivo. DESIGN: A membrane-based microdialyzer was first validated in vitro. The same device was tested afterward in a randomized, controlled animal experiment. SETTING: University experimental research laboratory. SUBJECTS: Twenty-four Landrace pigs of both genders. INTERVENTIONS: In vitro: Membrane microdialyzers were kept in warmed sodium lactate baths with lactate concentrations between 2 and 8 mmol/L for 10-120 mins, and microdialysis lactate concentrations were measured repeatedly (210 measurements). In vivo: An extracorporeal shunt with blood reservoir and roller pump was inserted between the proximal and distal abdominal aorta, and a microdialyzer was inserted intraperitoneally. In 12 animals, total splanchnic blood flow (measured by transit time ultrasound) was reduced by a median 43% (range, 13% to 72%) by activating the shunt; 12 animals served as controls. MEASUREMENTS AND MAIN RESULTS: In vitro: The fractional lactate recovery was 0.59 (0.32-0.83) after 60 mins and 0.82 (0.71-0.87) after 90 mins, with no further increase thereafter. At 60 and 90 mins, the fractional recovery was independent of the lactate concentration. In vivo: Abdominal blood flow reduction resulted in an increase in peritoneal microdialysis lactate concentration from 1.7 (0.3-3.8) mmol/L to 2.8 (1.3-6.2) mmol/L (p = .006). At the same time, mesenteric venous-arterial lactate gradient increased from 0.1 (-0.2-0.8) mmol/L to 0.3 (-0.3 -1.8) mmol/L (p = .032), and mesenteric venous-arterial Pco2 gradients increased from 12 (8-19) torr to 21 (11-54) torr (p = .005). CONCLUSIONS: Peritoneal membrane microdialysis provides a method for the assessment of splanchnic ischemia, with potential for clinical application.

Lactate and glucose concentrations in brain interstitial fluid, cerebrospinal fluid, and serum during experimental pneumococcal meningitis

Metabolic abnormalities during bacterial meningitis include hypoglycorrhachia and cerebrospinal fluid (CSF) lactate accumulation. The mechanisms by which these alterations occur within the central nervous system (CNS) are still incompletely delineated. To determine the evolution of these changes and establish the locus of abnormal metabolism during meningitis, glucose and lactate concentrations in brain interstitial fluid, CSF, and serum were measured simultaneously and sequentially during experimental pneumococcal meningitis in rabbits. Interstitial fluid samples were obtained from the frontal cortex and hippocampus by using in situ brain microdialysis, and serum and CSF were directly sampled. There was an increase of CSF lactate concentration, accompanied by increased local production of lactate in the brain, and a decrease of CSF-to-serum glucose ratio that was paralleled by a decrease in cortical glucose concentration. Brain microdialysate lactate concentration was not affected by either systemic lactic acidosis or artificially elevated CSF lactate concentration. These data support the hypothesis that the brain is a locus for anaerobic glycolysis during meningitis, resulting in increased lactate production and perhaps contributing to decreased tissue glucose concentration.

Methodological approach to the first and second lactate threshold in incremental cardiopulmonary exercise testing

Determination of an 'anaerobic threshold' plays an important role in the appreciation of an incremental cardiopulmonary exercise test and describes prominent changes of blood lactate accumulation with increasing workload. Two lactate thresholds are discerned during cardiopulmonary exercise testing and used for physical fitness estimation or training prescription. A multitude of different terms are, however, found in the literature describing the two thresholds. Furthermore, the term 'anaerobic threshold' is synonymously used for both, the 'first' and the 'second' lactate threshold, bearing a great potential of confusion. The aim of this review is therefore to order terms, present threshold concepts, and describe methods for lactate threshold determination using a three-phase model with reference to the historical and physiological background to facilitate the practical application of the term 'anaerobic threshold'.

Hypoglycemia despite hyperglycemia. Is a cerebral glucose deficiency possible even with raised blood sugar levels?

Hypoglycemia represents the most frequent endocrinologic emergency situation in prehospital patient care. As the patients are usually unconscious on arrival of emergency medical personnel, often the only way to establish a diagnosis is by determination of the blood glucose concentration. However, even normoglycemic or hyperglycemic levels cannot definitively exclude the diagnosis of a previous hypoglycemia as the cause of the acute cerebral deficiency. Therefore, and especially in the case of insulin-dependent diabetes mellitus, a differential diagnosis should be considered. We report a case of emergency treatment of a hypoglycemic episode in a female patient with prolonged neuroglycopenia together with cerebrovascular dementia and Alzheimer's disease.

Sources of familial aggregation and co-aggregation of fasting blood glucose and nutritional factors among Mexican -Americans in Starr County, Texas

The purpose of this study was to determine the effects of nutrient intake, genetic factors and common household environmental factors on the aggregation of fasting blood glucose among Mexican-Americans in Starr County, Texas. This study was designed to determine: (a) the proportion of variation of fasting blood glucose concentration explained by unmeasured genetic and common household environmental effects; (b) the degree of familial aggregation of measures of nutrient intake; and (c) the extent to which the familial aggregation of fasting blood glucose is explained by nutrient intake and its aggregation. The method of path analysis was employed to determine these various effects.^ Genes play an important role in fasting blood glucose: Genetic variation was found to explain about 40% of the total variation in fasting blood glucose. Common household environmental effects, on the other hand, explained less than 3% of the variation in fasting blood glucose levels among individuals. Common household effects, however, did have significant effects on measures of nutrient intake, though it explained only about 10% of the total variance in nutrient intake. Finally, there was significant familial aggregation of nutrient intake measures, but their aggregation did not contribute significantly to the familial aggregation of fasting blood glucose. These results imply that similarities among relatives for fasting blood glucose are not due to similarities in nutrient intake among relatives. ^

Cerebral energetics and the glycogen shunt: Neurochemical basis of functional imaging

Positron-emission tomography and functional MRS imaging signals can be analyzed to derive neurophysiological values of cerebral blood flow or volume and cerebral metabolic consumption rates of glucose (CMRGlc) or oxygen (CMRO2). Under basal physiological conditions in the adult mammalian brain, glucose oxidation is nearly complete so that the oxygen-to-glucose index (OGI), given by the ratio of CMRO2/CMRGlc, is close to the stoichiometric value of 6. However, a survey of functional imaging data suggests that the OGI is activity dependent, moving further below the oxidative value of 6 as activity is increased. Brain lactate concentrations also increase with stimulation. These results had led to the concept that brain activation is supported by anaerobic glucose metabolism, which was inconsistent with basal glucose oxidation. These differences are resolved here by a proposed model of glucose energetics, in which a fraction of glucose is cycled through the cerebral glycogen pool, a fraction that increases with degree of brain activation. The “glycogen shunt,” although energetically less efficient than glycolysis, is followed because of its ability to supply glial energy in milliseconds for rapid neurotransmitter clearance, as a consequence of which OGI is lowered and lactate is increased. The value of OGI observed is consistent with passive lactate efflux, driven by the observed lactate concentration, for the few experiments with complete data. Although the OGI changes during activation, the energies required per neurotransmitter release (neuronal) and clearance (glial) are constant over a wide range of brain activity.

Desempenho, mortalidade e escore fecal de bezerros aleitados com diferentes dietas líquidas e terapias de reidratação quando acometidos por diarreias

O objetivo deste trabalho foi avaliar o efeito da utilização de sucedâneo lácteo com alto conteúdo proteico de origem vegetal no desempenho e saúde de bezerros, e avaliar métodos de reidratação para o tratamento de diarreias. No primeiro estudo foram utilizados 33 bezerros da raça Holandês distribuídos nos tratamentos: 1) Alto volume e baixa proteína (AV/BP): 8 litros, 21,4% PB; 2) Alto volume e alta proteína (AV/AP): 8 litros, 23,7% PB e 3) Baixo volume e alta proteína (BV/AP): 6 litros, 23,7% PB. Os bezerros foram alojados em abrigos individuais, com livre acesso a água e concentrado. Não houve efeito dos tratamentos para o desempenho animal (P>0,05). Os tratamentos AV/BP e AV/AP resultaram em maior consumo de sucedâneo (P<0,05), mas não afetaram o consumo de concentrado nem o consumo total (P>0,05). O escore fecal foi maior (P>0,05) para animais nos tratamentos AV/AP e BV/AP. Os animais nos tratamentos AV/BP permaneceram maior número de dias em diarreia (P<0,05), em comparação aqueles aleitados com BV/AP, os quais tiveram menos dias com vida (P<0,05). A concentração de lactato foi maior (P<0,05) para animais nos tratamentos AV/BP e AV/AP enquanto a concentração de proteína total foi maior (P<0,05) nos tratamentos AV/BP e BV/AP. Sucedâneos com elevado conteúdo de proteína de origem vegetal afetam negativamente o desempenho de bezerros podendo levar o animal a morte. No segundo estudo foram comparados três soluções de hidratação oral quanto a sua eficiência em repor eletrólitos e água, além de manter o desempenho de bezerros. Foram utilizados 42 bezerros mestiços Holandês-Jersey, distribuídos nos tratamentos: 1) Soro comum, 2) Glutellac® e 3) Soro comum + Aminogut®. Os animais foram aleitados com 4 L/d de sucedâneo lácteo até a oitava semana de vida quando foram desaleitados de forma abrupta. As terapias de reidratação foram oferecidas quando os animais apresentavam escore fecal >= 3 na escala de 1 a 5. Não houve efeito das terapias de reidratação no desempenho nem em metabólitos sanguíneos (P>0,05). O consumo voluntário de água foi maior para os animais reidratados com Glutellac®, mas o consumo total maior para os animais reidratados com Soro comum. As concentrações de HCO3 e Na+ foram maiores para os animais no tratamento Glutellac® (P=0,088 e P=0,073 respectivamente), sendo a concentração de glicose também afetada pelo protocolo de hidratação (P<0,05). A concentração de HCO3 aumentou do primeiro para o segundo dia, a de K+ e glicose diminuíram do primeiro para o segundo dia, enquanto que o Beecf teve um comportamento variável segundo a terapia de reidratação utilizada. Houve efeito da interação tratamento x dia de avaliação apenas para a concentração de BUN (P<0,05). O pH, a concentração de Na+ e Beecf foram maiores em animais mais velhos, enquanto K+, hematócrito e hemoglobina, foram menores (P<0,05). O consumo voluntário de água foi maior em animais reidratados com Glutellac®, o que junto com a simplicidade de uso, representam as principais vantagens deste método de reidratação.

Some performance effects of age and low blood alcohol levels on a computerized neuropsychological test.

Federal Aviation Administration, Office of Aviation Medicine, Washington, D.C.

On-the-road driving behavior and breath alcohol concentration. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Determining the fetal scalp lactate level that indicates the need for intervention in labour

Background: Fetal scalp lactate testing has been shown to be as useful as pH with added benefits. One remaining question is What level of lactate should trigger intervention in the first stage of labour?' Aims: This study aimed to establish the lactate level in the first stage of labour that indicates the need for intervention to ensure satisfactory outcomes for both babies and mothers. Methods: A prospective study at Mater Mothers' Hospital, Brisbane, Australia, a tertiary referral centre. One hundred and forty women in labour, with non-reassuring fetal heart rate traces, were tested using fetal blood scalp sampling of 5 mu L of capillary blood tested on an Accusport (Boeringer, Mannheim, East Sussex, UK) lactate meter. Decision to intervene in labour was based on clinical assessment plus a predetermined cut off. Main outcome measures were APGAR scores, cord arterial pH, meconium stained liquor and Intensive Care Nursery admission. Results: Two-graph receiver operating characteristic (TG-ROC) analysis showed optimal specificity, and sensitivity for predicting adverse neonatal outcomes was a scalp lactate level above 4.2 mmol/L. Conclusions: Fetal blood sampling remains the standard for further investigating-non-reassuring cardiotocograph (CTG) traces. Even so, it is a poor predictor of fetal outcomes. Scalp lactate has been shown to be at least as good a predictor as scalp pH, with the advantages of being easier, cheaper and with a lower rate of technical failure. Our study, found that a cut off fetal scalp lactate level of 4.2 mmol/L, in combination with an assessment of the entire clinical picture, is a useful tool in identifying those women who need intervention.

Effects of starting strategy on 5-min cycling time-trial performance

The importance of pacing for middle-distance performance is well recognized, yet previous research has produced equivocal results. Twenty-six trained male cyclists (O2peak 62.8 ± 5.9 ml · kg-1 · min-1; maximal aerobic power output 340 ± 43 W; mean ± s) performed three cycling time-trials where the total external work (102.7 ± 13.7 kJ) for each trial was identical to the best of two 5-min habituation trials. Markers of aerobic and anaerobic metabolism were assessed in 12 participants. Power output during the first quarter of the time-trials was fixed to control external mechanical work done (25.7 ± 3.4 kJ) and induce fast-, even-, and slow-starting strategies (60, 75, and 90 s, respectively). Finishing times for the fast-start time-trial (4:53 ± 0:11 min:s) were shorter than for the even-start (5:04 ± 0:11 min:s; 95% CI = 5 to 18 s, effect size = 0.65, P < 0.001) and slow-start time-trial (5:09 ± 0:11 min:s; 95% CI = 7 to 24 s, effect size = 1.00, P < 0.001). Mean O2 during the fast-start trials (4.31 ± 0.51 litres · min-1) was 0.18 ± 0.19 litres · min-1 (95% CI = 0.07 to 0.30 litres · min-1, effect size = 0.94, P = 0.003) higher than the even- and 0.18 ± 0.20 litres · min-1 (95% CI = 0.5 to 0.30 litres · min-1, effect size = 0.86, P = 0.007) higher than the slow-start time-trial. Oxygen deficit was greatest during the first quarter of the fast-start trial but was lower than the even- and slow-start trials during the second quarter of the trial. Blood lactate and pH were similar between the three trials. In conclusion, performance during a 5-min cycling time-trial was improved with the adoption of a fast- rather than an even- or slow-starting strategy.

Drinking and driving in Vietnam : perceptions and risk

Road traffic injuries are a major global public health problem but continue to receive inadequate attention. Alcohol influences both risk and consequence of road traffic injury but the scale of the problem is not well understood in many countries. In Vietnam, economic development has brought a substantial increase in the number of registered motorcycles as well as alcohol consumption. Traffic injury is among the leading causes of death in Vietnam but there is little local information regarding alcohol related traffic injuries. The primary goal of this study is to explore the drinking and driving patterns of males and their perceptions towards drink-driving and to determine the relationship between alcohol consumption and road traffic injuries. Furthermore, this thesis aims to present the situation analysis for choosing priority actions to reduce drinking and driving in Vietnam. The study is a combination of two cross-sectional surveys and a pilot study. The pilot study, involving 224 traffic injured patients, was conducted to test the tools and the feasibility of approach methods. In the first survey, male patrons (n=464) were randomly selected at seven restaurants. Face-to-face interviews were conducted when patrons just arrived and breath tests were collected when they were about to leave the restaurant. In the second survey, male patients admitted to hospital following a traffic injury (n=480, of which 414 were motorcycle or bicycle riders) were interviewed and their blood alcohol concentration (BAC) measured by breathalyzer. The results show broadly similar patterns of drinking and driving among male patrons and male traffic injured patients with a high frequency of drinking and drink-driving reported among the majority of the two groups. A high proportion of male patrons were leaving restaurants with a BAC over the legal limit. Factors that significantly associate with the number of drinks and BAC were age, hazardous drinking, frequency of drink-driving in the past year, self-estimated number of drinks consumed to drive legally, perceived family’s disapproval of drink-driving, and perceived legal risk and physical risk. The proportion of patrons and patients with BAC above the legal limit of 0.05 were 86.7% and 60.4% respectively, which was much higher than found in previous studies. In addition, both groups had a high prevalence of BAC over 0.15g/100ml (39.7% of patrons and 45.6% patients), a level that can seriously affect driving capacity. Results from the case-crossover analysis for patients indicate a dose-response relationship between alcohol consumption and the risk of traffic injury. The risk of traffic injury increased when alcohol was consumed before driving and there was a more than 13 fold increase when six or more drinks were consumed. Regarding perceptions towards drinking and driving, findings corroborate the low awareness among males in Vietnam, with a majority of respondents holding a low knowledge of safe and legally permissible alcohol use, and a low perceived risk of drinking and driving. The results also indicate a huge gap in prevention skills in terms of planning ahead or using alternative transport to avoid drink-driving and a perception by patrons and patients of a low rate of disapproval of drink-driving from peers and family. Findings in this study have considerable implications for national policy, injury prevention, clinical practice, reporting systems, and for further research. The low rate of compliance with existing laws and a generally low perceived legal risk toward drink-driving in this study call for the strengthening of enforcement along with mass media campaigns and news coverage in order to decrease the widespread perception of impunity and thereby, to reduce the level of drink-driving. In addition, no significant difference was found in this study on risk of traffic injuries between car drivers and motorcycle drivers. The current inconsistency between legal BAC for drivers of motorcycles, compared to cars, thus needs addressing. Furthermore, as drinking was found to be very common, rather than solely targeting drink-driving, it is important to call for a more strategic and comprehensive approach to alcohol policy in Viet Nam. This study also has considerable implications for clinical practice in terms of screening and brief interventions. Our study suggests that the short form of the AUDIT (AUDIT-C) screening tool is appropriate for use in busy emergency departments. The high proportion of traffic injured patients with evidence of alcohol abuse or hazardous drinking suggests that brief interventions by alcohol and drug counselors in emergency departments are a sensible option to addressing this important problem. The significance of this study is in the combination of the systematic collection of breath test and use of case-crossover design to estimate the risk of traffic injuries after alcohol consumption. The results provide convincing evidence to policy makers, health authorities and the media to help raise community awareness and policy advocacy toward the drinkdriving problem in Vietnam. The findings suggest an urgent need for a multi-sectoral approach to curtail drink-driving in Vietnam, especially programs to raise community awareness and effective legal enforcement. Furthermore, serving as a situation analysis, the thesis should inform the formulation of interventions designed to curtail drinking and driving in Vietnam and other developing countries.