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The sarcolemmal lactate transporter: transmembrane determinants of lactate flux.

Lactic acid is produced and consumed under various metabolic and pathogenic conditions in numerous cell types of mammalian tissues. The movement of lactic acid and lactate anions within and between tissues depends, ultimately, on flux rates between intracellular and extracellular compartments. Flux rates themselves are dependent on several variables, including (but not limited to) exchange surface area, flow through the tissues of interest, lactate and proton concentration gradients across the cell membranes, and proton concentration gradients across the cell membranes, and permeability of the membranes to these ions. This review focuses on the selective permeability characteristics of the principal cells of lactate metabolism: skeletal muscle, heart, liver, kidney, and erythrocytes. Special attention will be paid to lactate uptake and release in skeletal muscle, the premier tissue of lactate production and consumption, and the regulator of whole body lactate dynamics during exercise and recovery from exercise.

Biological Transport↗

Incidence and duration of lactation and lactational performance among mothers of low-birth-weight and term infants.

The lactation experience of 55 mothers of 62 infants of low birth weight (2500 g or less) was prospectively compared with that of 55 mothers of 55 control infants (38 weeks' gestation or more, birth weight more than 2500 g) born at the same institution. The incidence rates of lactation at delivery were 73% for the control group and 58% for the low-birth-weight group; 11% of the infants of low birth weight fed breast milk were never put to the breast. The mean age at first suckling was 277.3 hours in the low-birth-weight group, compared with 3.3 hours in the control group (p less than 0.0005). At first suckling 81% of the low-birth-weight infants and 25% of the control infants sucked poorly or refused the breast (p less than 0.001). At discharge 65% of the breast-milk-fed control infants were exclusively breast-fed, compared with 3% of the low-birth-weight infants fed breast milk (p less than 0.001). The incidence rates of lactation over time were similar in the control and low-birth-weight groups (51% v. 44% at 1 month, 29% v. 13% at 3 months, 13% v. 4% at 6 months and 4% v. 2% at 12 months). The mean duration of lactation was 3.2 months for the control group and 2.5 months for the low-birth-weight group. In the long term 37% of the low-birth-weight infants fed breast milk failed to breast-feed, compared with 2% of the control infants, and only 31% were exclusively breast-fed, compared with 85% of the control infants (p less than 0.001). However, the degree of satisfaction with the lactation experience was similar in the two groups. We conclude that mothers of low-birth-weight infants have good potential for lactation.

Breast Feeding↗

Ultrastructural changes of the pancreatic beta-cell and the insulin secretion by islets from lactating and non-lactating rats.

Islets isolated from lactating rats, as compared to islets from non-lactating rats, release less insulin when incubated in the absence of exogenous nutrient or presence of either D-glucose (11.1 mM) or the association of L-leucine and L-glutamine (10.0 mM each). The insulin content of the islets is not different in lactating and non-lactating rats. The volume density of the dark granules in the beta-cells is not at variance in both groups. However the volume density of the light (pale) granules is significantly lower in the lactating rats. The reduced amount of light granules is in keeping with the reduced secretory capacity of the beta-cells from lactating rats.

Animals↗

[The clinical picture of lactate acidosis. 1 : Lactate metabolism].

The definition of lactate acidosis (lactic acidosis) is discussed. The metabolism of lactate and pyruvate are described. An increase in lactate concentration should be called lactic acidemia (lactate emia). This increase in lactate concentration can be caused either by an increased production (primarily by the so-called peripheral tissues) or by a decreased utilization (by the liver or by the kidneys). Therefore, various metabolic alterations can cause lactate acidosis.

Acidosis↗

Heart rate deflection compared to 4 mmol x l(-1) lactate threshold during incremental exercise and to lactate during steady-state exercise on an arm-cranking ergometer in paraplegic athletes.

The deflection point (DP) of the heart rate in relation to the work rate (WR) of 8 male endurance-trained paraplegics and 11 male physically active sports students was investigated during nonsteady-state incremental arm cranking ergometry (IT) and compared to the 4 mmol x l(-1) blood lactate concentration threshold and to blood lactate concentration in steady-state exercise (SST). Heart rate, and lactate concentration from capillary blood, were determined at rest, during IT and SST. The DP was calculated by linear regression analysis of the heart rate during IT. The SST consisted of three consecutive exercise intensities over a period of 8 min at exercise intensities of 10 W below, and at 10 W above the work rate at deflection point (WRDP). No difference was found between the paraplegics and non-handicapped subjects regarding heart rate and blood lactate concentration at rest and during exercise. A DP was established in all the paraplegics and in 72.7% of the non-handicapped subjects, but lactate accumulation was observed in 75% of the paraplegics and in 62.5% of the non-handicapped subjects at the lowest intensity of SST. In summary, endurance-trained paraplegics with an injury level below T5 showed heart rate and blood lactate concentration values comparable to non-handicapped subjects during IT. A linear increase at moderate exercise intensities and a levelling-off at higher to maximal intensities could be identified in all the paraplegics and in 72.7% of non-handicapped subjects. The determination of the anaerobic threshold by DP should be applied with caution, since no causal relationship of DP and the anaerobic threshold was found and the WRDP tended to overestimate threshold values.

Adult↗

Assessment of blood lactate: practical evaluation of the Biosen 5030 lactate analyzer.

PURPOSE: The aim of this study was to assess the validity and reliability of the Biosen 5030 lactate analyzer compared with a YSI 2300 lactate analyzer and a Kodak Ektachem DTII in a practical laboratory study context. METHODS: To assess validity, 144 triplicate capillarized blood samples, across a range of values, were analyzed using the three analyzers. To assess reliability a further 665 samples were repeat analyzed. Temporal stability was determined by the reanalysis of resting and maximal exercise blood samples, after a period of storage ranging from 7 to 20 h, at room temperature. To measure inter- and intra-investigator reliability, 20 resting samples were taken from three different subjects by different investigators and a coefficient of variation was determined. RESULTS: There were strong relationships between the Biosen, the YSI (r2 = 0.97), and the Kodak Ektachem (r2 = 0.91). An analysis of Biosen compared with YSI revealed a positive bias of 0.37 mmol x L(-1) (95% limits of agreement, -0.85 to 1.59 mmol x L(-1)). The test-retest reliability correlation was significant (r2 = 0.99, P < 0.05), but a paired t-test revealed a small (0.03 mmol x L(-1), P < 0.05) significant difference. The coefficient of variation from the three investigators across the 20 samples ranged from 1.3 to 3%. Blood lactate concentration in resting blood samples did significantly increase in value (0.2 mmol x L(-1), P < 0.05) after 7-h exposure to the air, whereas there was no change in maximal exercise blood lactate values after 20-h exposure to the air. CONCLUSIONS: In a practical context, the Biosen 5030 lactate analyzer was comparable to the other analyzers giving fast reliable measures of blood lactate concentrations over the full range of values, which remained stable over extended periods at room temperature.

Bias↗

Changes in Lactate-Producing and Lactate-Utilizing Bacteria in Relation to pH in the Rumen of Sheep During Stepwise Adaptation to a High-Concentrate Diet.

Changes in the numbers and types of lactate-producing and lactate-utilizing bacteria in the rumen of sheep were followed during stepwise adaptation from a low- to a high-concentrate diet. The mean numbers of bacteria increased after each change in diet when increasing amounts of maize grain were substituted for maize stover. A surge in number of amylolytic bacteria always preceded an increase in lactate-utilizing bacteria, and with the final diet containing 71% grain and molasses the two groups tended to balance each other, which resulted in low lactic acid accumulation. The lactate utilizers thus played a key role in controlling the fermentation. Orderly shifts occurred among the predominating amylolytic and lactate-utilizing bacteria in response to the gradual decrease in ruminal pH as the amount of maize meal in the diet increased. Among the lactate utilizers, the succession began with acid-sensitive Veillonella and Selenomonas, which were superseded by more acid-tolerant Anaerovibrio and Propionibacterium. Among the amylolytic bacteria, Bacteroides was superseded by more acid-tolerant Lactobacillus and Eubacterium. The ecological succession of predominating genera was shown to be correlated significantly with ruminal pH and, more specifically, with the length of time as well as the extent to which the pH remained below a certain critical undefined value in the rumen, arbitrarily set at pH 6.00.

Journal Article↗

Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients.

INTRODUCTION: Acid-base abnormalities are common in the intensive care unit (ICU). Differences in outcome exist between respiratory and metabolic acidosis in similar pH ranges. Some forms of metabolic acidosis (for example, lactate) seem to have worse outcomes than others (for example, chloride). The relative incidence of each type of disorder is unknown. We therefore designed this study to determine the nature and clinical significance of metabolic acidosis in critically ill patients. METHODS: An observational, cohort study of critically ill patients was performed in a tertiary care hospital. Critically ill patients were selected on the clinical suspicion of the presence of lactic acidosis. The inpatient mortality of the entire group was 14%, with a length of stay in hospital of 12 days and a length of stay in the ICU of 5.8 days. RESULTS: We reviewed records of 9,799 patients admitted to the ICUs at our institution between 1 January 2001 and 30 June 2002. We selected a cohort in which clinicians caring for patients ordered a measurement of arterial lactate level. We excluded patients in which any necessary variable required to characterize an acid-base disorder was absent. A total of 851 patients (9% of ICU admissions) met our criteria. Of these, 548 patients (64%) had a metabolic acidosis (standard base excess < -2 mEq/l) and these patients had a 45% mortality, compared with 25% for those with no metabolic acidosis (p < 0.001). We then subclassified metabolic acidosis cases on the basis of the predominant anion present (lactate, chloride, or all other anions). The mortality rate was highest for lactic acidosis (56%); for strong ion gap (SIG) acidosis it was 39% and for hyperchloremic acidosis 29% (p < 0.001). A stepwise logistic regression model identified serum lactate, SIG, phosphate, and age as independent predictors of mortality. CONCLUSION: In critically ill patients in which a measurement of lactate level was ordered, lactate and SIG were strong independent predictors of mortality when they were the major source of metabolic acidosis. Overall, patients with metabolic acidosis were nearly twice as likely to die as patients without metabolic acidosis.

Acidosis↗

Serum-ethanol determination: comparison of lactate and lactate dehydrogenase interference in three enzymatic assays.

Gas chromatography is considered to be the reference method for ethyl alcohol determination. However, enzymatic ethanol assays have been developed for use in the clinical laboratory by several commercial vendors. Essentially, these assays utilize the oxidation of ethyl alcohol to acetaldehyde with concurrent reduction of nicotinamide adenine dinucleotide (NAD) to NADH while monitoring the increase in absorbance at 340 nm. The increase in absorbance is theoretically proportional to the ethanol concentration in the sample. Previously, several authors reported that increased concentrations of lactate and lactate dehydrogenase (LDH) can cause false-positive results with certain enzymatic ethyl alcohol assays. In the present investigation, we further studied the interference of lactate and LDH in three enzymatic assays. Apparent ethyl alcohol concentrations in serum spiked with lactate and LDH, as well as patient and autopsy samples, were determined by the Syva, Abbott, and Roche enzymatic assays and by gas chromatography. The effect of coenzyme depletion on the rate of reaction and the interference of hemolysis were also investigated. Based on our results we suggest that coenzyme depletion plays a major role in the severity of the false-positive ethyl alcohol result, and the interference from hemolysis has a negligible effect on these results. We also confirm the previous studies in showing that elevated serum-lactate and LDH concentrations can result in varying degrees of false-positive ethyl alcohol concentrations in the three enzymatic assays. This should be taken into consideration in the management of patients in a tertiary care medical center.

Catalysis↗

The relationship between gastric carcinoma and gastric juice lactate (L + D) and lactate dehydrogenase.

L-Lactate, D-lactate, and lactate dehydrogenase (LDH) levels were measured in the resting gastric juice of 73 patients and mean levels were found to be significantly higher in patients with gastric carcinoma than in those with benign gastric ulcer or those with normal stomachs. Raised levels of gastric juice L-lactate (greater than 1.3 mmol/l), D-lactate (greater than 0.15 mmol/l), and LDH (greater than 55 IU/1) were seen in 14 of 27 patients with carcinomas, two of 15 with benign ulcers, and six of 31 controls. Both L/D-lactate and LDH levels correlated with tumor size and depth of invasion. While six problem cases with large gastric lesions were correctly diagnosed using these indices, there was only poor sensitivity and moderate specificity, as early cancers had normal L/D-lactate and LDH levels, and these indices were raised in a significant number of controls. Thus while it is of interest that L/D-lactate and LDH are elevated in the gastric juice of patients with gastric carcinoma there appears to be little optimism for using these indices in the early diagnosis of gastric neoplasia.

Adult↗

Effects of cold acclimation on the activity levels of creatine kinase, lactate dehydrogenase and lactate dehydrogenase isoenzymes in various tissues of the rat.

The effects of cold acclimation on the activity levels of creatine kinase, lactate dehydrogenase and lactate dehydrogenase isoenzymes in various tissues/ organs of the rat (Rattus norvegicus) were investigated. Male Sprague-Dawley rats were divided into two groups. One group was housed at 4+/-1 degrees C (experimental group) and the other at 24+/-1 degrees C (control group) for six months. The rats were housed in single cages and had access to food and water ad libitum. The tissues/organs investigated were heart, liver, lung, kidney, gastrocnemius muscle and interscapular brown adipose tissue as well as serum. With the exception of lung, (which showed a decrease of 24%) total creatine kinase activity levels were significantly increased (P< 0.05) in all the tissues/organs investigated (17-51%) as well as serum (34%), in cold acclimated animals. Cold acclimation also resulted in significantly increased (P< 0.05) activity levels of lactate dehydrogenase in all the tissues/organs investigated (14-24%) as well as serum (35%). Cold exposure resulted in an increase of the activity levels of all the detectable isoenzymes of lactate dehydrogenase, although not always significant, in all the tissues/organs investigated as well as serum. The M(4)tetramer of lactate dehydrogenase was the only detectable isoenzyme in serum.

Acclimatization↗

Effect of dietary modifications on lactate threshold and onset of blood lactate accumulation during incremental exercise.

To assess the effect of dietary change on (1) the point at which arterial blood lactate concentration (HLa) increases above the resting value (lactate threshold) and (2) the fixed point corresponding to 4 mM of HLa (onset of blood lactate accumulation; OBLA), five healthy male subjects were put on a mixed diet for 3 days, followed by 4 days of a low carbohydrate diet (a low CHO diet), and then 3 days of a high carbohydrate diet (a high CHO diet). Following each type of diet, the subjects performed a progressive bicycle exercise test, during which concentrations of HLa, pyruvate, FFA, and glucose were analyzed from serial samples of arterial blood, and VO2 was obtained by the Douglas bag method. The results of this study are as follows: FFA was significantly lower, while pyruvate was significantly higher at rest after a high CHO diet than after a low CHO diet (P less than 0.05). These differences continued throughout the incremental exercise, which indicates the incremental contribution of CHO to metabolism after a high CHO diet and vice versa. There was no significant difference in lactate threshold expressed in VO2 among the three conditions. VO2 obtained at OBLA was significantly lower after a high CHO diet than after a low CHO diet (P less than 0.01). It was concluded that the dietary modifications used in this study had no influence on lactate threshold but did affect the point of OBLA. Therefore, dietary conditions should be considered when OBLA is determined using a fixed 4-mM HLa method.

Adult↗

[The effect of alimentary vitamin B6 supply during pregnancy and lactation on the activity of specific transaminases of lactating rats].

Eighty female Sprague-Dawley rats weighing 257 g were fed during gravidity a semi-synthetic diet containing five vitamin-B6-treatment groups (0.6, 3, 6, 18 and 180 mg/kg diet). The daily food intake was 14 g. During the following lactation the rats of each treatment group were divided into two groups containing 3 and 6 mg vitamin B6. At the 14th day of lactation the dams were decapitated. Parameters for determination of the vitamin-B6-status were activity of AST and ALT in plasma, erythrocytes and liver. The average activity of AST in plasma was 549 U/l, in erythrocytes 1939 U/l and liver 106 U/g fresh matter (FM). The increasing vitamin-B6-supplementation during gravidity resulted in an elevated activity of AST between lowest and highest treatment group in plasma 56%, erythrocytes 44%, and in liver 43%, respectively. In response to the increasing vitamin-B6-treatment during lactation the activity of AST in plasma increased for 19%, in erythrocytes for 13%, and in liver for 24%, respectively. A low vitamin-B6-supply (0.6 mg/kg diet) during gravidity in combination with demand-oriented supply during lactation (6 mg/kg diet) initiated the highest increase of activity. A deficient vitamin-B6-supply during lactation (3 mg/kg diet) could be compensated with optimal vitamin-B6-supply during gravidity. The values of ALT-activity showed no significant differences between the graded vitamin-B6-supplements, as a result of a high coenzyme saturation.

Alanine Transaminase↗

Responses to systemic angiotensin II in lactating and non-lactating goats.

This study aimed at investigating whether lactation affects the dipsogenic, hypertensive and volumetric effects of angiotensin II (Ang II) in a low-yielding goat adapted to arid conditions. Six black Moroccan goats were given intravenous infusions of Ang II at 8 ng kg-1 min-1 for 90 min during lactation and a non-lactation period. To further test the dipsogenic response, 5 of them were given Ang II at the consecutively increasing doses 10, 20, 50 and 100 ng kg-1 min-1 (10 min at each dose). The body weight was 32 +/- 1 kg in both periods and the daily milk production was 22 +/- 2 ml kg-1. No drinking was observed during infusions of Ang II in any of the goats. The rise of the mean arterial pressure to Ang II was attenuated in lactating animals and this was not steroid-dependent since the plasma progesterone level was low (< 0.2 nmol 1(-1)). Total plasma protein concentration decreased during Ang II infusions, and the ratio albumin/total proteins was unchanged, indicating that haemodilution had occurred. It is concluded that Ang II does not elicit drinking in the arid adapted Moroccan goats and we suggest that these goats have an elevated thirst threshold. However, haemodilution and an attenuated blood pressure response to Ang II occur in the lactating Moroccan goat, as has previously been observed in high-yielding Swedish domestic goats.

Angiotensin II↗

Aerobic training effects on maximum oxygen consumption, lactate threshold and lactate disappearance during exercise recovery of dogs.

1. Dogs were submitted to an aerobic training schedule and its maximum oxygen consumption, lactate threshold and lactate concentration during recovery were compared among the following conditions: not trained (UT), after 1 month of training (T1), after 2 months of training (T2) and after detraining (DT). 2. Maximum oxygen consumption increased significantly in relation to UT condition only at T2 condition. The detraining reversed this alteration. 3. Lactate threshold when expressed as Vo2 or absolute work load increased significantly after aerobic training (T2) but did not present any alteration when it was expressed as % of Vo2 max. 4. The lactate decreasing during recovery did not differ between the four experimental conditions (after 10 min). 5. The latency time for the lactate concentration to reach the top values was reduced by aerobic training (T2).

Animals↗

Variations in the susceptibility of lactating and non-lactating bovine udders to infection when infused with Escherichia coli.

Small numbers of Escherichia coli were infused into both lactating and non-lactating udders. Twelve of the 17 lactating quarters infused became infected, and all 12 showed clinical symptoms of udder disease. The 5 lactating quarters which did not become infected all had pre-infusion somatic cell counts greater than 300000 cells/ml milk, whilst all the quarters which became infected had cell counts less than 300000 cells/ml milk. E. coli was subsequently recovered from only 6 of the 16 non-lactating quarters infused. In only 2 of these quarters did clinical infection follow, both quarters being in a cow infused 2 d before calving. The remaining 4 quarters from which E. coli was recovered were all negative within 5 d of infusion. These differences in susceptibility are discussed, particularly with reference to the frequent occurrence of coliform mastitis at and shortly after calving.

Animals↗

Lactate stress testing by bedside lactate determination.

Lactate determination for the lactate-stress-test (LST) by means of a bedside method has not been performed. Serum lactate was determined by means of the Ektachrome Clinical Chemistry Slide (LST1) and bedside by means of the Acutrend Lactate (LST2) once before, 3 times during, and once after a 15-min, constant 30-W workload on a bicycle in 20 controls, 21 disease controls, and 22 patients with mitochondriopathy (MCP). Lactate's upper reference limits at rest, 5, 10, 15 min after starting, and 15 min after finishing the exercise were 2.0, 1.9, 1.9, 1.8, and 1.5 mmol/L for the LST1 and 2.5, 2.9, 2.5, 2.7, and 2.0 mmol/L for the LST2. The LSTI (LST2) was abnormal in 17 (18) MCP patients, 7 (3) disease controls, and none (none) of the healthy subjects. The sensitivity of the LST1 (LST2) for MCP patients was 77% (82%). The specificity of the LST1 (LST2) was 67% (86%). Sensitivity and specificity of the LST2 are higher than that of the LST1. The LST2 can thus replace the LST1, since it is also easier to handle, quick, reliable, and cheaper.

Adult↗