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PubMed1999

Maturational changes in cerebral lactate and acid clearance following ischemia measured in vivo using magnetic resonance spectroscopy and microdialysis.

Intraischemic hyperglycemia has different effects on neurologic outcome in mature vs. immature brain, and may reflect differences in the extent or duration of cerebral lactic acidosis. We examined the hypotheses that post-ischemic lactate and acid clearance rates depend on the severity of intraischemic cerebral acidosis, and that rates of clearance change as a function of brain maturation. In vivo 31P and 1H magnetic resonance spectroscopy (MRS) was used to compare intracellular acid and lactate clearance rates in newborn and 1-month old swine following a 14-min episode of transient near-complete global ischemia. In the same animals, in vivo microdialysis was used to determine if extracellular lactate clearance changed as a function of cerebral lactic acidosis or differed between age groups following ischemia. Plasma glucose concentration was altered in individual animals to study a range of intraischemic cerebral lactic acidosis. For both age-groups, maximal brain acidosis and lactosis occurred in the post-ischemia interval, indicating a delay in the re-establishment of oxidative metabolism following ischemia. Clearance half-lives of both cerebral acidosis and lactosis increase as a function of increased intraischemic cerebral acidosis. For either age group, the clearance half-life for acidosis was faster than the half-life for lactate. However, the subgroup of 1-month old swine who experienced severe cerebral acidosis (i.e., pH<6.1) had a longer cerebral lactate clearance half-life as compared to the subgroup of newborn animals with a similar severity of acidosis. In both age groups, there were comparable maximal increases in extracellular lactate concentrations in the post-ischemic period and similar rates of decline from the maximum. These results demonstrate that post-ischemic lactate and acid clearance are altered by the extent of intraischemic acidosis, and the extent of post-ischemic uncoupling between brain acid and lactate clearance increases with advancing age. The transmembrane clearance of lactate was not a prominent mechanism that differentiated lactate clearance rates between newborn and 1-month old swine.

Acidosis, Lactic↗
PubMedDate not supplied

Lactate as a pivotal element in neuron-glia metabolic cooperation.

Lactate has been considered for a long time as a metabolic waste and/or a sign of hypoxia in the central nervous system. Nevertheless, clear evidence that lactate can constitute an adequate energy substrate for brain tissue has been provided as early as in the 1950s with the pioneering work of McIlwain in brain slices. Over the years, several studies using different approaches have confirmed that lactate is efficiently oxidized by brain cells in vitro. Moreover, lactate has been shown under certain circumstances to have a neuroprotective effect and support neuronal activity. Similar confirmation of lactate utilization in vivo as well as putative neuroprotection in various excitotoxic models has been provided. Lactate was even shown to restore cognitive performance upon an hypoglycemic episode in humans. More recently, it was proposed that lactate could be produced by astrocytes and released in the extracellular space to form a pool readily available for neurons in case of high energy demands. Several elements support the concept of a lactate shuttle between astrocytes and neurons in the central nervous system. Among them, the description of specific monocarboxylate transporters found on both astrocytes and neurons is an important observation consistent with this concept. Interestingly, lactate shuttles between different cell types within the same organ have been described outside the central nervous system, notably in muscle and testis. Thus, lactate is emerging as a valuable intercellular exchange molecule in different systems including the brain where it might be an essential element of neuron-glia metabolic interactions.

Central Nervous System↗
PubMed1998

Novel system for real-time ex vivo lactate monitoring in human whole blood.

The objective of the study was to evaluate the performance of an amperometric enzyme based lactate sensor and to investigate the possibility of replacing a double lumen catheter based blood withdrawal system with a heparin coated single lumen system. The inner lumen of a double lumen catheter which was placed in a peripheral vein was perfused with heparin solution. The outer lumen was used to collect heparinized blood samples at a defined flow rate. The single lumen system was attached to a heparinized catheter which was also placed in a peripheral vein. The undiluted blood samples were collected at a specified flow rate. A sensor flow chamber incorporating an amperometric thin-film lactate microbiosensor was placed in the sampling line for real-time lactate monitoring. Plasma lactate concentrations were measured during frequently performed hyperlactatemia bicycle ergometer experiments in six healthy volunteers (age 25.8 +/- 2.8 years, BMI 22.7 +/- 1 kg/m2). Additionally, plasma lactate was measured in real-time using the lactate sensors. The first three experiments were performed with a double lumen based catheter system whereas the following three experiments were performed with a heparin coated catheter system. The correlation coefficients of sensor readings and laboratory analyzer results in all six experiments were between 0.93 and 0.99, respectively (P < 0.001). The miniaturized lactate sensors showed a linear range up to 25 mmol/l lactate concentration and 95% response times < 30 s in undiluted serum. During the experiments maximum lactate concentrations of 14 mmol/l were achieved. Improvements of system performance using heparin coated catheter systems could be shown. The overall SD of the sensor readings compared to laboratory results using three double lumen catheter based systems was 0.91 mmol/l whereas the SD using three heparin coated systems was 0.65 mmol/l. In summary, real-time monitoring of lactate in human whole blood is feasible with such a device and can be improved by using heparin coated catheter systems.

Adult↗
PubMed2004

Serum L-lactate and pyruvate in HIV-infected patients with and without presumed NRTI-related adverse events compared to healthy volunteers.

BACKGROUND: Nucleoside reverse transcriptase inhibitors (NRTIs) used in antiretroviral therapy may cause mitochondrial toxicity. Mitochondrial dysfunction leads to disturbance of the glucose metabolism, resulting in an accumulation of L-lactate (L) and pyruvate (P), with an enhanced L/P ratio. OBJECTIVES: We analysed lactate and pyruvate blood samples of patients of our outpatient department. Aim of the analysis was to detect preliminary mitochondrial toxicity in patients on antiretroviral nucleoside analogues, which might result in disturbances of L, P, L/P ratio, bicarbonate (Bic) or beta-hydroxybutyrate/aceto-acetate (beta-HB/AA) ratios. STUDY DESIGN: Blood samples of L, P, Bic, beta-HB and AA were analysed in four groups of subjects. The first group (A) consisted of patients with presumed NRTI-related adverse events (n=21), the second group (B) consisted of patients without adverse events (n=28), the third group (C) were HIV-infected patients without antiretroviral therapy (n=6) and the last group (D) were healthy controls (n=12). The mean duration of NRTI-treatment was 18 months (range 0-78 months). RESULTS: The mean lactate level in group A was 2319 micromol/l (S.D. +/-1231, median 1741 micromol/l), in group B 1257 micromol/l (S.D. +/-607, median 1087), Group C 1285 (S.D. +/-451, median 1245 micromol/l) and 951 micromol/l (S.D. +/-270, median 979) in the healthy controls. No significant differences in pyruvate, L/P, Bic and beta-HB/AA were seen in the four groups. The mean lactate level in patients on stavudine was 1980 micromol/l (S.D. +/-1197) versus 1051 micromol/l (S.D. +/-395, P=0.01) in patients on zidovudine. All patients with lactate values above 2700 micromol/l (eight) experienced adverse events. CONCLUSION: Lactate levels were higher in patients with presumed NRTI-related adverse events. Furthermore, HIV patients receiving a stavudine containing antiretroviral therapy had higher lactate values than patients without stavudine. Although routine lactate measurement in all patients on antiretroviral therapy is not recommended, lactate measurement might be useful for follow up of patients with presumed NRTI-related adverse events and in patients with lactate levels above 2500 micromol/l. These patients require extra surveillance to evaluate if discontinuation of the current antiretroviral therapy is needed.

Adult↗
PubMed2001

Myocardial lactate release after intracoronary verapamil application in humans: acute effects of intracoronary verapamil on systemic and coronary hemodynamics, myocardial metabolism, and norepinephrine levels.

Coronary and systemic hemodynamic effects of verapamil have been investigated previously in detail. The acute impact of intracoronary verapamil on coronary hemodynamics has, however, not been correlated to simultaneously changes in myocardial metabolism or norepinephrine levels in humans. After bolus application of 1 mg verapamil into the left coronary artery of 52 patients scheduled for routine coronary angiography, heart rate (HR) remained unchanged, whereas mean arterial blood pressure (MAP) decreased (93.8 +/- 14.9 mmHg to 85.1 +/- 13.7 mmHg, p = 0.001). Coronary blood flow (CBF), calculated from intracoronary Doppler measurements and quantitative coronary angiography, increased after verapamil administration (28.5 +/- 16.7 ml/min to 66.2 +/- 41.8 ml/min, p < 0.001), whereas coronary vascular resistance index (CVRI) decreased (1.43 +/- 0.92 to 0.46 +/- 0.23, p < 0.001). Blood samples, taken simultaneously from the aorta (Ao) and coronary sinus (CS) at baseline and at maximal flow velocity, showed an increase in norepinephrine concentrations in Ao (209 +/- 151 ng/l to 283 +/- 195 ng/l, p < 0.001) and CS (233 +/- 162 ng/l to 323 +/- 248 ng/l, p = 0.004). Myocardial metabolism of pyruvate and free fatty acids were not affected. Glucose release was augmented and initial lactate consumption changed to a net lactate release into the CS (Ao to CS differences: glucose: -1.92 +/- 9.9 mg/dl to -12.8 +/- 22.8 mg/dl, p < 0.001; lactate: 0.07 +/- 0.2 mmol/l to -0.08 +/- 0.3 mmol/l, p = 0.001). Similar results were obtained for the extraction ratios and flux of these metabolites. There was a weak correlation between the increase in CBF and lactate release into the CS. This is the first report of unexpected myocardial lactate release following intracoronary verapamil administration in humans. This lactate release was paralleled by an increased glucose release into the CS at an unchanged metabolism of free fatty acids and pyruvate. One explanation for this unexplained lactate release during increased coronary blood flow might be a wash out phenomenon of lactate from previous ischemic areas, other explanations might be the induction of paradox myocardial ischemia and/or a steal effect. Further studies are necessary to explain these unexpected findings of increased coronary flow and myocardial lactate release. Until reliable explanations are pending, studies using only lactate release as a marker of myocardial ischemia, without taken coronary and systemic hemodynamic parameters into account, should be interpreted with caution.

Adult↗
PubMed2001

The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: The Fremantle Diabetes Study.

AIMS: To determine (i) which factors, including metformin, are associated with the fasting plasma lactate concentration in type 2 diabetes, and (ii) whether plasma lactate is associated with haemodynamic and metabolic effects. METHODS: We measured fasting plasma lactate in 272 well-characterized diabetic patients from a community-based sample, 181 (67%) of whom were taking metformin with or without other therapies. Linear regression analysis was used to identify predictors, including metformin therapy, of the plasma lactate, and to investigate associations between plasma lactate and resting pulse rate and serum bicarbonate. Factor analysis assessed independent relationships between groups of cosegregating variables. RESULTS: Metformin-treated patients had higher plasma lactate concentrations than nonmetformin-treated subjects (geometric mean [s.d. range] 1.86 [1.34-2.59] vs 1.58 [1.09-2.30] mmol x l(-1), respectively; P < 0.001). In a linear regression model, plasma glucose, BMI and metformin use (but not dose) were independently associated with plasma lactate (P < or = 0.028); after adjustment for the former two variables, metformin-treated patients had a mean plasma lactate 0.16 mmol l-1 greater than in subjects not taking the drug. Factor analysis revealed that plasma lactate, plasma glucose, BMI and pulse rate cosegregated but serum bicarbonate was not in this grouping. CONCLUSIONS: The present results show that metformin therapy increases the fasting plasma lactate in ambulant patients with type 2 diabetes from a community-based cohort. From associations in the data we hypothesize that this increase reflects (i) increased sympathetic activity in patients with the metabolic syndrome (ii) increased substrate (glucose) availability and (iii) a direct metformin effect.

Aged↗
PubMed1998

Lactate transport in L6 skeletal muscle cells and vesicles: allosteric or multisite mechanism and functional membrane marker of differentiation.

Membrane lactate transport was studied in skeletal muscle cells and membrane vesicles from the L6 line in relation to in vitro myogenesis. In myoblasts, lactate was transported by simple diffusion and insensitive to classical inhibitors: a positive correlation between onset of creatine kinase activity and lactate transport in differentiated myotubes was observed and could be considered to be a functional marker of cell differentiation. In myotubes, complete analysis of the velocity curves (direct coordinates, Eadie-Scatchard plots, Hill plots) gave parameters showing that lactate was carried by an allosteric or multisite system. This was confirmed by using sarcolemmal vesicles and specific inhibitors. In whole cells, alpha-cyano-4-hydroxycinnamic acid (CIN) and parachloromercuribenzylsulphonic acid (pCMBS) inhibited the maximal velocity without modifying the global cooperativity of the system. The weak effect of 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), which has a low affinity constant (Ki = 22.5 microM), implicated the monocarboxylate system rather than the anionic exchanger as a carrier system in muscle cells. CIN and DIDS exhibited one type of interaction with lactate carriers, and the curvilinear shape of the lactate Hill plot with or without inhibitors suggested that inhibitors were active at the same family of interaction sites and had a common range of affinities. The apparent competitive inhibition of pyruvate (Ki = 3.2 mM) did not modify the transport pathway of lactate in L6 myotubes. In conclusion, kinetic analysis of lactate transport in the presence or absence of inhibitors gave evidence for a multisite lactate carrier activity in myotubes composed of two systems at least, related to two or three isoforms of lactate carriers.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Interstitial lactate levels in human skin at rest and during an oral glucose load: a microdialysis study.

In vitro data have suggested that the skin is a significant lactate source. The purpose of the present study was to measure lactate and glucose concentrations in intact human skin in vivo using the microdialysis technique. Microdialysis fibres of 216 microns were inserted intradermally and perfused at a rate of 3 microliters min-1. In the first experimental protocol, dialysis fibres were calibrated by the method of no net flux in eight subjects. Skin lactate concentrations of 2.48 +/- 0.17 mmol l-1 were significantly greater than lactate concentrations of 0.84 +/- 0.15 mmol l-1 in venous plasma (P < 0.01). Glucose concentrations in skin and venous plasma were similar (5.49 +/- 0.18 vs. 5.26 +/- 0.24 mmol l-1). In the second experimental protocol, changes in lactate and glucose levels were studied in 10 subjects after an oral glucose tolerance test (OGTT). After the OGTT, plasma glucose and lactate levels increased by 54% and 39% to peak levels at 30 and 60 min respectively. In comparison, skin glucose and lactate increased by 41% and 18% at 60 and 90 min. No changes in skin blood flow were observed during the OGTT. The data suggest that resting skin is a significant lactate source with no significant lactate production during OGTT. The cellular source of lactate in the skin remains undetermined to date.

Blood Glucose↗
PubMed2005

Serum lactate level has prognostic significance after pediatric cardiac surgery.

OBJECTIVE: The determination of postoperative course after cardiac surgery has always been a challenging issue. It is more sophisticated in the pediatric age group. The aim of this investigation was to identify whether increased concentrations of lactate in arterial blood has a predictive value for postoperative morbidity and mortality after heart surgery. METHODS: From May 2002 to June 2003, 60 infants operated on at the authors' institution were included in this prospective study. The patients were divided into 2 groups according to their respective postoperative serum lactate values. After the stabilization period in the intensive care unit (first 3 hours postoperatively), samples for serum lactate were obtained from arterial blood at 3 (t1), 6 (t2), and 12 hours (t3) postoperatively. The patients were subdivided into 2 groups according to their respective mean serum lactate values. A value of 4.8 mmol/L (3 times the normal upper limit) was chosen as a threshold for serum lactate. The patients with a mean value of greater than 4.8 mmol/L (group 1) were compared with the remaining group of patients (group 2). The relationship between serum mean lactate level and intraoperative and postoperative clinical variables was evaluated. RESULTS: Among the patients in this study, 26 (43.3%) had a serum mean lactate level more than 4.8 mmol/L and 34 (56.7%) had a level of 4.8 mmol/L or less. Age, aortic cross-clamping time, cardiopulmonary bypass time, and the lowest hematocrit during cardiopulmonary bypass were significant variables that influenced the postoperative serum mean lactate level. Six patients died in the postoperative period and 54 infants survived. The hospital mortality was significantly higher in group 1 than in group 2 (19.0% v 2.9%; p = 0.037, kappa = 0.179). Multivariate analysis revealed that serum mean lactate level correlated significantly with inotrope score, intubation time, and intensive care unit stay. CONCLUSIONS: Blood lactate concentration of 4.8 mmol/L or higher during the early postoperative hours identifies a group of patients with increased risk of postoperative morbidity and mortality.

Cardiac Surgical Procedures↗
PubMed2006

Lactate elimination and glycogen resynthesis after intense bicycling.

OBJECTIVE: Muscles break down glycogen to lactate during intense exercise, and in the recovery period, glycogen reappears while lactate disappears. The purpose of this study was to examine to what extent lactate is resynthesized to glycogen within the formerly active muscles themselves in man. MATERIAL AND METHODS: Fifteen healthy young men cycled for 2 min to exhaustion. Muscle biopsies were taken from the knee extensor muscle before the exercise, just after the ride, and again after 45 min of recovery. In addition, blood samples were taken from the femoral artery and vein, and the leg blood flow was measured using the ultrasound Doppler technique. The muscle biopsies were analysed for glycogen, lactate and other metabolites, and the blood samples were analysed for lactate and glucose. The exchanges of lactate and glucose of the leg were assessed by multiplying the measured arterio-venous (a-v) differences by the blood flow. RESULTS: During the exercise the muscles broke down 20+/-4 mmol glycogen kg(-1) wet muscle mass and produced 26+/-1 mmol lactate kg(-1). In the recovery period after 24+/-1 mmol lactate kg(-1) had disappeared, of which 48 % was released to the blood, 52 % disappeared within the muscle. An R-value of 0.62 across the leg suggests that none of the lactate was oxidized. Altogether, 10+/-3 mmol glycogen kg(-1) reappeared during recovery. Glucose uptake accounted for 2 mmol kg(-1) and glycolytic intermediates (G-6-P and free glucose) accounted for 4 mmol kg(-1); 4 mmol glycogen kg(-1) (42 %) reappeared from unknown sources. CONCLUSIONS: The present data are compatible with the idea that around half of the lactate produced during intense bicycling is resynthesized to glycogen within the working muscles themselves in the recovery period after the bicycling.

Adult↗
PubMed1997

The Conconi test in not valid for estimation of the lactate turnpoint in runners.

Conconi et al. (1982) reported that an observed deviation from linearity in the heart rate-running velocity relationship determined during a field test in runners coincided with the 'lactate threshold'. The aim of this study was to assess the validity of the original Conconi test using conventional incremental and constant-load laboratory protocols. Fourteen trained male distance runners (mean +/-s: age 22.6 +/- 3.4 years; body mass 67.6 +/- 4.8 kg; peak VO2 66.3 +/- 4.7 ml kg-1 min-1) performed a standard multi-stage test for determination of lactate turnpoint and a Conconi test on a motorized treadmill. A deviation from linearity in heart rate was observed in nine subjects. Significant differences were found to exist between running velocity at the lactate turnpoint (4.39 +/- 0.20 m s-1) and at deviation from linear heart rate (5.08 +/- 0.25 m s-1) (P < 0.01), and between heart rate at the lactate turnpoint (172 +/- 10 beats min-1) and at deviation from linearity (186 +/- 9 beats min-1) (P < 0.01). When deviation of heart rate from linearity was evident, it occurred at a systematically higher intensity than the lactate turnpoint and at approximately 95% of maximum heart rate. These results were confirmed by the physiological responses of seven subjects, who performed two constant-velocity treadmill runs at 0.14 m s-1 below the running velocity at the lactate turnpoint and that at which the heart rate deviated from linearity. For the lactate turnpoint trial, the prescribed 30 min exercise period was completed by all runners (terminal blood lactate concentration of 2.4 +/- 0.5 mM), while the duration attained in the trial for which heart rate deviated from linearity was 15.9 +/- 6.7 min (terminal blood lactate concentration of 8.1 +/- 1.8 mM). We concluded that the Conconi test is invalid for the non-invasive determination of the lactate turnpoint and that the deviation of heart rate from linearity represents the start of the plateau at maximal heart rate, the expression of which is dependent upon the specifics of the Conconi test protocol.

Adult↗
PubMed2000

The lactate-dependent enhancement of hydroxyl radical generation by the Fenton reaction.

The effect of lactic acid (lactate) on Fenton based hydroxyl radical (*OH) production was studied by spin trapping, ESR, and fluorescence methods using DMPO and coumarin-3-carboxylic acid (3-CCA) as the *OH traps respectively. The *OH adduct formation was inhibited by lactate up to 0.4 mM (lactate/iron stoichiometry = 2) in both experiments, but markedly enhanced with increasing concentrations of lactate above this critical concentration. When the H2O2 dependence was examined, the DMPO-OH signal was increased linearly with H2O2 concentration up to 1 mM and then saturated in the absence of lactate. In the presence of lactate, however, the DMPO-OH signal was increased further with higher H2O2 concentration than 1 mM, and the saturation level was also increased dependent on lactate concentration. Spectroscopic studies revealed that lactate forms a stable colored complex with Fe3+ at lactate/Fe3+ stoichiometry of 2, and the complex formation was strictly related to the DMPO-OH formation. The complex formation did not promote the H2O2 mediated Fe3+ reduction. When the Fe3+ -lactate (1:2) complex was reacted with H2O2, the initial rate of hydroxylated 3-CCA formation was linearly increased with H2O2 concentrations. All the data obtained in the present experiments suggested that the Fe3+-lactate (1:2) complex formed in the Fenton reaction system reacts directly with H2O2 to produce additional *OH in the Fenton reaction by other mechanisms than lactate or lactate/Fe3+ mediated promotion of Fe3+/Fe2+ redox cycling.

Coumarins↗
PubMed1997

Lactate and the effects of exercise on testosterone secretion: evidence for the involvement of a cAMP-mediated mechanism.

The effects of swimming and lactate on the release of testosterone were examined in male rats. During in vivo experiments, male rats were catheterized via the right jugular vein and blood was collected at 0, 10, 15, 30, and 60 min following the exercise, or they were catheterized via the right jugular vein and the left femoral vein and blood was collected at 0, 2, 5, 10, 15, 30, 60, and 120 min after a 10-min infusion at lactate (13 mg.kg-1.min-1). Trunk blood and blood from the testicular vein were also collected after 10 min of swimming or water immersion. In an in vitro experiment, testicular fragments were challenged with lactate (0.01-10 mM) and/or human chorionic gonadotropin (hCG; 0.5 IU.mL-1), and the mediobasal hypothalamus (MBH) was challenged with lactate (8 mM). The post-exercise levels of plasma lactate and testosterone at 10, 15, and 30 min were higher than resting levels. Plasma luteinizing hormone (LH) was increased following 30 min of swimming. Administration of lactate or hCG increased in a dose dependent manner testicular cyclic adenosine 3':5' monophosphate (cAMP) and testosterone release. Plasma testosterone increased after swimming and lactate infusion. Incubation of MBH with lactate increased the gonadotropin-releasing hormone (GnRH) level in the medium. These results suggest that the increased plasma testosterone levels in male rats during exercise is at least partially a result of a direct and LH-independent stimulatory effect of lactate on the secretion of testosterone by increasing testicular cAMP production. Swim-elevated plasma LH may be a result of a rise of GnRH caused by lactate.

Animals↗
PubMed2000

Intra- and extra-cellular lactate shuttles.

The "lactate shuttle hypothesis" holds that lactate plays a key role in the distribution of carbohydrate potential energy that occurs among various tissue and cellular compartments such as between: cytosol and mitochondria, muscle and blood, blood and muscle, active and inactive muscles, white and red muscles, blood and heart, arterial blood and liver, liver and other tissues such as exercising muscle, intestine and portal blood, portal blood and liver, zones of the liver, and skin and blood. Studies on resting and exercising humans indicate that most lactate (75-80%) is disposed of through oxidation, with much of the remainder converted to glucose and glycogen. Lactate transport across cellular membranes occurs by means of facilitated exchange along pH and concentration gradients involving a family of lactate transport proteins, now called monocarboxylate transporters (MCTs). Current evidence is that muscle and other cell membrane lactate transporters are abundant with characteristics of high Km and Vmax. There appears to be long-term plasticity in the number of cell membrane transporters, but short-term regulation by allosteric modulation or phosphorylation is not known. In addition to cell membranes, mitochondria also contain monocarboxylate transporters (mMCT) and lactic dehydrogenase (mLDH). Therefore, mitochondrial monocarboxylate uptake and oxidation, rather than translocation of transporters to the cell surfaces, probably regulate lactate flux in vivo. Accordingly, the "lactate shuttle" hypothesis has been modified to include a new, intracellular component involving cytosolic to mitochondrial exchange. The intracellular lactate shuttle emphasizes the role of mitochondrial redox in the oxidation and disposal of lactate during exercise and other conditions.

Animals↗
PubMed1997

Modulation of skeletal muscle lactate metabolism following bacteremia by insulin or insulin-like growth factor-I: effects of pentoxifylline.

Hyperlactatemia is a frequent complication of sepsis. We investigated the effect of pentoxifylline on plasma lactate concentrations and lactate release by epitrochlearis incubated in vitro following intravenous injection of Escherichia coli. Plasma lactate concentrations were elevated on day 2 postinfection and remained elevated for at least another 4 days. Lactate production by incubated epitrochlearis was not increased in septic rats on day 2 postinfection, and lactate production from muscles incubated with insulin (2 nM) or insulin-like growth factor-I, (10 nM) was similar in control and septic rats. On day 6 postinfection, lactate production was augmented 1.8-fold in muscles from septic rats and both insulin and IGF-I caused an exaggerated stimulation of lactate production compared with control. Pentoxifylline decreased plasma TNF concentrations 100-fold following injection of bacteria and prevented the sepsis-induced hyperlactatemia and increase in lactate production by incubated muscles in presence or absence of insulin or IGF-I. Thus, pentoxifylline prevented the sepsis-induced abnormalities in skeletal muscle lactate production and plasma lactate concentrations.

Animals↗
PubMed2006

D-lactate is not a reliable marker of gut ischemia-reperfusion in a rat model of supraceliac aortic clamping.

OBJECTIVE: D-lactate is the dextrorotatory form of L-lactate. L-lactate is the isomer routinely tested in clinical practice to assess cell hypoxemia. D-lactate has been recently proposed as a specific marker of gut ischemia-reperfusion (IR), particularly after surgery for ruptured aortic aneurysms. We sought to assess D-lactate as a reliable marker of gut IR in a rat model of supraceliac aortic clamping. DESIGN: Prospective, randomized trial. SETTING: Animal research center. SUBJECTS: Male Wistar rats. INTERVENTIONS: After general anesthesia, rats were randomized into two groups (n = 8 in each). The IR group underwent a laparotomy, aortic clamping for 40 mins, and 1 hr of reperfusion. The control group underwent the same procedure, except for aortic clamping. MEASUREMENTS AND MAIN RESULTS: The following variables were tested after 1 hr of reperfusion (IR group) or after the equivalent time (control group): 1) tissue and cell insult via ileum morphometry and electron microscopy, serum glutamic transaminases (serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase), pH, and L-lactate; 2) systemic inflammatory response via tumor necrosis factor-alpha; and 3) D-lactate levels. After IR, mucous membrane thickness and villi height decreased significantly, respectively by 30% and 45%, and electron-microscopic examination showed typical IR mucous membrane cell insult. IR also caused lactic acidosis (pH = 7.16 +/- 0.05 vs. 7.31 +/- 0.02, p < .01; L-lactate = 7.1 +/- 1.6 vs. 1.6 +/- 0.4 mmol/L, p = .001) and increased blood levels of transaminases. Concurrently, the inflammatory response was characterized by an increase in tumor necrosis factor-alpha (213 +/- 129 vs. 47 +/- 32 pg/mL, p < .05). However, blood levels of D-lactate never increased after IR. CONCLUSIONS: D-lactate is not a reliable marker of gut IR in our model of supraceliac aortic clamping in rats.

Animals↗
PubMed1974

Enzymes related to lactate metabolism in green algae and lower land plants.

Cell-free extracts of Chlorella pyrenoidosa contained two enzymes capable of oxidizing d-lactate; these were glycolate dehydrogenase and NAD(+)-dependent d-lactate dehydrogenase. The two enzymes could be distinguished by differential centrifugation, glycolate dehydrogenase being largely particulate and NAD(+)-d-lactate dehydrogenase being soluble. The reduction of pyruvate by NADH proceeded more rapidly than the reverse reaction, and the apparent Michaelis constants for pyruvate and NADH were lower than for d-lactate and NAD(+). These data indicated that under physiological conditions, the NAD(+)-linked d-lactate dehydrogenase probably functions to produce d-lactate from pyruvate.Lactate dehydrogenase activity dependent on NAD(+) was found in a number of other green algae and in the green tissues of a few lower land plants. When present in species which contain glycolate oxidase rather than glycolate dehydrogenase, the enzyme was specific for l-lactate rather than d-lactate. A cyclic system revolving around the production and utilization of d-lactate in some species and l-lactate in certain others is proposed.

Journal Article↗
PubMed2006

Competition between glucose and lactate as oxidative energy substrates in both neurons and astrocytes: a comparative NMR study.

Competition between glucose and lactate as oxidative energy substrates was investigated in both primary cultures of astrocytes and neurons using physiological concentrations (1.1 mm for each). Glucose metabolism was distinguished from lactate metabolism by using alternatively labelled substrates in the medium ([1-13C]glucose + lactate or glucose + [3-13C]lactate). After 4 h of incubation, 1H and 13C-NMR spectra were realized on perchloric acid extracts of both cells and culture media. For astrocytic cultures, spectra showed that amino acids (glutamine and alanine) were more labelled in the glucose-labelled condition, indicating that glucose is a better substrate to support oxidative metabolism in these cells. The opposite was observed on spectra from neuronal cultures, glutamate being much more labelled in the lactate-labelled condition, confirming that neurons consume lactate preferentially as an oxidative energy substrate. Analysis of glutamine and glutamate peaks (singlets or multiplets) also suggests that astrocytes have a less active oxidative metabolism than neurons. In contrast, they exhibit a stronger glycolytic metabolism than neurons as indicated by their high lactate production yield. Using a mathematical model, we have estimated the relative contribution of exogenous glucose and lactate to neuronal oxidative metabolism. Under the aforementioned conditions, it represents 25% for glucose and 75% for lactate. Altogether, these results obtained on separate astrocytic and neuronal cultures support the idea that lactate, predominantly produced by astrocytes, is used as a supplementary fuel by neurons in vivo already under resting physiological conditions.

Animals↗