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PubMed1980

Relation of Na+ reabsorption to utilization of O2 and lactate in the perfused rat kidney.

When the ratio delta TNa+/delta QO2 is used to estimate the energy requirements for net Na+ reabsorption (TNa+), it is assumed that the entire change in renal O2 uptake (delta QO2) is utilized only for the delta TNa+. However, if increases in renal synthetic work also occur when TNa+ is increased, the energy cost for TNa+ will be overestimated. We perfused the substrate-limited isolated rat kidney at 38 degrees C, pH 7.4, a mean arterial pressure of 120 mmHg, and mean lactate concentrations between 0 and 8.3 mM. We measured QO2, TNa+, net reabsorption of lactate (Tlac), net utilization of lactate (Qlac), lactate decarboxylation rate (Qlacox), as well as the net entry rate of lactate into biosynthetic pathways (Qxslac). When no exogenous substrate was present (rates are means, g wet wt-1 . min-1) GFR was 351 +/- 38 microliter, %TNa+ was 54 +/- 2%, and QO2 was 2.85 +/- 0.31 mumol; there was also a loss of about 20% of renal tissue K+ content. When mean [lactate] greater than or equal to 0.73 mM, the loss of tissue K+ was completely prevented and %TNa+ increased to and remained at about 85%. At mean [lactate] of 8.3 mM, Tlac was 5.1 +/- 0.6 mumol, QO2 was 6.12 +/- 1.24 mumol, and GFR was 709 +/- 83 microliter. Qlac, delta Qlacox and delta TNa+ increased in parallel with each other and approaches maximal rates as [lactate] was raised. By contrast, Tlac increased as a linear function of perfusate [lactate] and was not related to changes in Qlac. The molar increases in TNa+ were 10- to 20-fold greater than the increases in Tlac. It is more probable, therefore, that lactate enhances TNa+ by providing energy from its oxidation rather than by a co-transport phenomenon. At all concentrations of lactate, more lactate was utilized (Km = 1.2 mM; Vmax = 3.4) than was decarboxylated (Km = 1.6 mM; Vmax = 1.7), indicating that as lactate concentration increased, both the synthesis of new products from lactate and Na+ reabsorption increased. We conclude that the ratio delta TNa+/delta QO2, overestimates the energy cost of Na+ reabsorption. In order to obtain an accurate estimate of the energy requirements for TNa+ in kidney, the simultaneous changes in the rate of net biosynthetic work must also be quantified as TNa+ is changed.

Absorption↗
PubMed1996

Intracellular lactate- and pyruvate-interconversion rates are increased in muscle tissue of non-insulin-dependent diabetic individuals.

The contribution of muscle tissues of non-insulin-dependent diabetes mellitus (NIDDM) patients to blood lactate appearance remains undefined. To gain insight on intracellular pyruvate/lactate metabolism, the postabsorptive forearm metabolism of glucose, lactate, FFA, and ketone bodies (KB) was assessed in seven obese non-insulin-dependent diabetic patients (BMI = 28.0 +/- 0.5 kg/m2) and seven control individuals (BMI = 24.8 +/- 0.5 kg/m2) by using arteriovenous balance across forearm tissues along with continuous infusion of [3-13C1]-lactate and indirect calorimetry. Fasting plasma concentrations of glucose (10.0 +/- 0.3 vs. 4.7 +/- 0.2 mmol/liter), insulin (68 +/- 5 vs. 43 +/- 6 pmol/liter), FFA (0.57 +/- 0.02 vs. 0.51 +/- 0.02 mmol/liter), and blood levels of lactate (1.05 +/- 0.04 vs. 0.60 +/- 0.06 mmol/liter), and KB (0.48 +/- 0.04 vs. 0.29 +/- 0.02 mmol/liter) were higher in NIDDM patients (P < 0.01). Forearm glucose uptake was similar in the two groups (10.3 +/- 1.4 vs. 9.6 +/ 1.1 micromol/min/liter of forearm tissue), while KB uptake was twice as much in NIDDM patients as compared to control subjects. Lactate balance was only slightly increased in NIDDM patients (5.6 +/- 1.4 vs. 3.3 +/- 1.0 micromol/min/liter; P = NS). A two-compartment model of lactate and pyruvate kinetics in the forearm tissue was used to dissect out the rates of lactate to pyruvate and pyruvate to lactate interconversions. In spite of minor differences in the lactate balance, a fourfold increase in both lactate- (44.8 +/- 9.0 vs. 12.6 +/- 4.6 micromol/min/liter) and pyruvate-(50.4 +/- 9.8 vs. 16.0 +/- 5.0 micromol/min/liter) interconversion rates (both P < 0.01) were found. Whole body lactate turnover, assessed by using the classic isotope dilution principle, was higher in NIDDM individuals (46 +/- 9 vs. 21 +/- 3 micromol/min/kg; P < 0.01). Insights into the physiological meaning of this parameter were obtained by using a whole body noncompartmental model of lactate/pyruvate kinetics which provides a lower and upper bound for total lactate and pyruvate turnover (NIDDM = 46 +/- 9 vs. 108 +/- 31; controls = 21 +/- 3 - 50 +/-13 micromol/min/kg). In conclusion, in the postabsorptive state, despite a trivial lactate release by muscle, lactate- and pyruvate-interconversion rates are greatly enhanced in NIDDM patients, possibly due to concomitant impairment in the oxidative pathway of glucose metabolism. This finding strongly suggest a major disturbance in intracellular lactate/pyruvate metabolism in NIDDM.

Adult↗
PubMed2002

Bench-to-bedside review: lactate and the kidney.

The native kidney has a major role in lactate metabolism. The renal cortex appears to be the major lactate-consuming organ in the body after the liver. Under conditions of exogenous hyperlactatemia, the kidney is responsible for the removal of 25-30% of all infused lactate. Most of such removal is through lactate metabolism rather than excretion, although under conditions of marked hyperlactatemia such excretion can account for approximately 10-12% of renal lactate disposal. Indeed, nephrectomy results in an approximately 30% decrease in exogenous lactate removal. Importantly and differently from the liver, however, the kidney's ability to remove lactate is increased by acidosis. While acidosis inhibits hepatic lactate metabolism, it increases lactate uptake and utilization via gluconeogenesis by stimulating the activity of phospho-enolpyruvate carboxykinase. The kidney remains an effective lactate-removing organ even during endotoxemic shock. The artificial kidney also has a profound effect on lactate balance. If lactate-buffered fluids are used in patients who require continuous hemofiltration and who have pretreatment hyperlactatemia, the serum lactate levels can significantly increase. In some cases, this increase can result in an exacerbation of metabolic acidosis. If bicarbonate-buffered replacement fluids are used, a significant correction of the acidosis or acidemia can also be achieved. The clinician needs to be aware of these renal effects on lactate levels to understand the pathogenesis of hyperlactatemia in critically ill patients, and to avoid misinterpretations and unnecessary or inappropriate diagnostic or therapeutic activities.

Acidosis↗
PubMed1997

Hepatic and gastrointestinal oxygen and lactate metabolism during low cardiac output in lambs.

We previously observed young lambs to be more tolerant of hypoxia; compared with older lambs, they accumulate lactate at a slower rate during comparable reduction in cardiac output, and have a greater percent decrease in cardiac output before onset of systemic lactate accumulation. To determine the mechanism of lactic acidosis and the cause for this "tolerance," we reduced cardiac output progressively in seven chronically catheterized conscious lambs (16.4 + 5.1 d) and measured hepatic and gastrointestinal (GI) blood flow (radioactive microspheres) and delivery, uptake, and extraction of lactate and O2. Hepatic O2 consumption declined proportionately below a critical hepatic O2 delivery (approximately 2 mL O2/min/kg), corresponding to the systemic O2 delivery associated with the onset of systemic lactate accumulation. As hepatic O2 delivery decreased below the critical value, there was initially net hepatic lactate uptake and then a change to net production when the O2 delivery decreased below approximately 1 mL O2/min kg. The GI tract had net lactate production at rest, but surprisingly switched to lactate uptake as cardiac output decreased. The mechanism of lactic acidosis was failure of hepatic lactate uptake to increase despite increased hepatic lactate delivery, as reported in adults subjects. However, in contrast, there was "true" hepatic dysfunction and lactate production only at the lowest levels of cardiac output, after onset of systemic lactate accumulation. Moreover, we speculate that tolerance of young lambs to hypoxia is at least due to two factors: 1) hepatic lactate uptake is maintained beyond the "critical" O2 delivery and fall in hepatic O2 consumption, and 2) there is a switch to lactate uptake by the GI tract serving to buffer the lactate.

Acidosis, Lactic↗
PubMed1988

In vivo lactate kinetics at rest and during recovery from exhaustive exercise in coho salmon (Oncorhynchus kisutch) and starry flounder (Platichthys stellatus).

A bolus injection of [14C]lactate was used to measure lactate turnover rates at rest and during recovery from exhaustive exercise in coho salmon (Oncorhynchus kisutch) and starry flounder (Platichthys stellatus). At rest, lactate turnover rate in salmon was almost double that in flounder (1.33 versus 0.76 mumol min-1 kg-1), which reflected the higher blood lactate level in salmon (1.00 versus 0.12 mmol l-1). From 2 to 4 h after exercise, when blood lactate levels were at their peak and constant, turnover rates were elevated in both species, though to a greater extent in salmon than in flounder (11.88 versus 2.27 mumol min-1 kg-1). Lactate concentration and turnover rate were linearly correlated in both species. The higher turnover rate in salmon was solely a consequence of the higher blood lactate levels since, at similar blood lactate concentrations, turnover rates in flounder and salmon were the same. Therefore, the lower blood lactate levels in flounder after exercise were not a consequence of higher turnover. In neither species was the turnover rate adequate to account for the rate of lactate clearance from the muscle, suggesting a large portion was retained within the muscle and metabolized in situ. Furthermore, following injection of [14C]lactate, greater than 80% of the total blood activity was recovered as lactate, indicating that little label was incorporated into other products (e.g. glucose). These data suggest that the Cori cycle plays a minimal role in the metabolism of lactate in salmon and flounder. Furthermore, at least in flounder, there was no correlation between the kinetics of lactate clearance and O2 consumption, suggesting that the classical concept of 'O2 debt' is not applicable in this species.

Animals↗
PubMed1997

Moderate food restriction reduces serum IGF-I and alters circulating IGF-binding protein profiles in lactating rats.

The role of somatogenic and lactogenic hormones in the adaptative mechanisms which occur in response to nutrient restriction during lactation is unknown. To characterize the effect of food restriction during lactation on serum IGF-I, GH and prolactin concentrations and serum IGF-binding protein (IGFBP) profiles, lactating dams had free access to food (control) or were restricted to 60% of control intake during pregnancy and lactation (RPL) or only during lactation (RL). Serum, milk and mammary gland samples were collected throughout lactation. RL dams lost body weight, control dams gained weight, while RPL dams maintained body weight during lactation. By day 20, body and mammary gland weights of RL and RPL dams did not differ and were lower than control (P < 0.05). Serum IGF-I concentrations in restricted groups were lower than control (P < 0.05), however, hepatic expression of IGF-I mRNA did not differ between groups in early (day 1) or mid-lactation (day 8) and was increased on day 20 in RL dams compared with RPL or control. These data suggest that serum IGF-I and hepatic IGF-I mRNA expression are not co-ordinately regulated in the food-restricted lactating rat. In early lactation, serum IGFBP-3 was lower in RPL dams than control (P < 0.05), whereas IGFBP-1 and -2 were increased in RL and RPL dams in late lactation compared with control. The decrease in IGFBP-3 and increase in lower molecular weight IGFBP may have contributed to the reduction in serum IGF-I by increasing IGF-I clearance from the circulation. Serum GH and prolactin were measured in samples obtained between 0900 and 1200 h. Serum GH did not differ with the exception of an increase on day 1 in control relative to RPL dams and on day 20 in RL dams relative to RPL and control. Serum prolactin was higher in the RL dams than controls on day 4. In summary, food restriction during pregnancy and lactation or solely during lactation results in similar reductions in serum IGF-I and alterations in serum IGFBP despite differences in body weight responses to food restriction during lactation.

Animals↗
PubMed1997

Additive effects of lactation and food restriction to increase hypothalamic neuropeptide Y mRNA in rats.

Neuropeptide Y (NPY) is the most powerful appetite stimulant known, and rates of synthesis and release in the hypothalamus correlate closely with nutritional status. Pregnancy and lactation provide an excellent model of physiological hyperphagia. In this study the authors measured food intake, plasma glucose, insulin and luteinizing hormone (LH) and hypothalamic NPY mRNA in rats during pregnancy and in early and late lactation. The effect of food restriction (to 80% of control) during lactation was also studied. Pregnancy resulted in a modest increase in daily food intake over non-lactating controls (controls: 15.6 +/- 0.6 g, pregnant: 19.8 +/- 1.1 g, P < 0.01). During lactation food intake increased dramatically to 355% of non-lactating levels by the 12th day. Insulin and glucose levels were unchanged in lactation, except in the food-restricted animals, when insulin levels were reduced to 49.5 +/- 18.4 pmol/l compared with 215 +/- 55 pmol/l (P < 0.01) in lactating, non-restricted animals, and glucose was reduced to 3.7 +/- 0.2 mmol/l compared with 5.1 +/- 0.2 mmol/l in non-restricted lactating animals. Hypothalamic NPY mRNA was unchanged in pregnancy, moderately increased after 5 days lactation (130 +/- 6.2% of control, P < 0.01) and increased further at 14 days lactation (179 +/- 14%, P < 0.001). The greatest changes occurred in the animals who were food-deprived during lactation, when hypothalamic NPY mRNA levels reached 324 +/- 44% (P < 0.001) of non-lactating levels. Increases in hypothalamic NPY synthesis may be partly responsible for the increase in food intake seen in lactation, but unlike in food deprivation, the increase is not related to circulating insulin, suggesting involvement of other regulatory factors.

Animals↗
PubMed2004

Visceral tissue growth and proliferation during the bovine lactation cycle.

Twenty one multiparous, nonpregnant, lactating dairy cows were used to assess the impact of stage of lactation on visceral tissue mass and small intestinal cell proliferation. Cows were slaughtered at each of 4 stages of lactation: 14, 90, 120, and 240 d of lactation. With stage of lactation, DMI increased through d 90 and thereafter remained similar through d 240 (quadratic). Carcass weight and empty body weight (EBW) declined with stage of lactation through d 120 and increased thereafter (quadratic). As a percentage of EBW, rumen, small intestine, and liver weights increased with increasing stage of lactation (quadratic), increasing from 14 to 120 d and declining through 240 d. Stage of lactation did not have a measurable affect on reticulum, omasum, abomasum, or large intestine weights as a percentage of EBW. Visceral adipose mass as a percentage of EBW declined with stage of lactation to a minimum at 120 d and increased by 240 d (quadratic). Concentrations of RNA and DNA of digestive tract organs were largely unaffected by stage of lactation with the exception of the liver DNA concentration through d 120 (quadratic). The proliferative growth fraction (Ki67) was unaffected by stage of lactation. However, bromo-deoxyuridine labeling of jejunal crypts exhibited a cubic response with stage of lactation and tritiated thymidine incorporation by duodenal epithelium increased with stage of lactation through d 120, declining thereafter (quadratic). Mass of visceral tissues increase to meet the energetic demands of lactation and that increased absorption capacity of the intestines is achieved by hyperplastic growth of the intestinal epithelium.

Animals↗
PubMed2006

Dry period length to maximize production across adjacent lactations and lifetime production.

The primary objectives of this research were to determine the dry period lengths that maximize production across adjacent lactations and also dry period length that maximizes lifetime yield. Effect of days dry (DD) after lactations 1 through 3 were determined separately for both adjacent lactation sums and lifetime yield. Field data, collected through the Dairy Herd Improvement Association, on US Holstein cows first calving between January 1997 and January 2004 were utilized. Lifetime records were restricted to cows first calving no later than December 1999. Actual lactation yields, in contrast to standardized records, were used to calculate lactation sums and lifetime records. Herds were required to be on test for the entire period to avoid partial records. Another important edit was that actual calving dates had to agree with expected calving dates, based on reported days open, within 10 d. This edit ensured that the producer knew, at least at one point in time, when the cow was going to calve. Cow effects were corrected for in both the adjacent lactation and lifetime analyses. The minimum DD to maximize production across adjacent lactations depended on parity. For yield across first and second lactations, there was little loss in production with a minimum of 40 to 45 DD. Longer dry periods (55 to 65 DD) were required after second and third lactations however, presumably due to the lower persistency of second and later lactation cows. Lifetime production was maximized by 40 to 50 DD after first lactation and 30 to 40 DD after second and later lactations. Fewer DD were required to maximize lifetime yield than adjacent lactation yield because cows with fewer DD also had more lifetime days in milk. Although dry periods of 30 to 40 d can be used after second and later lactations without cost in lifetime yield, their benefit to lifetime production is minimal. Dry periods shorter than 30 d or longer than 70 d are costly to lifetime yield and should be avoided. Dry periods longer than 80 d are even more costly than dry periods less than 30 d.

Animals↗
PubMed1987

A lactation measure of somatic cell count.

Adjustments and weights to combine individual sample day SCC into a lactation measure were developed from 182,446 Holstein lactation records completed in 1984 from herds primarily in the western United States. Data included 1,660,782 sample day SCC expressed as log base 2 scores. Stage of lactation effects were investigated within average lactation score. Curves for lactations with averages less than 3.5 were essentially identical, which indicated that effect of stage of lactation did not increase with average somatic cell score. Lactations with averages above 4.5 did not display the typical curve of an early minimum followed by a gradual increase and, therefore, were excluded from estimating effects of stage of lactation and season. Curve for lactations with an average somatic cell score of 4.0 was intermediate. Small season effects were detected; scores were lowest in February and March and highest in August, September, and October. Parties after first had similar curves for effect of stage of lactation, but first parity showed relatively little increase in late lactation. Weightings were developed to combine adjusted sample day scores into a lactation measure. Weights were squares of correlations (computed from sample days grouped by month) between adjusted score for a given sample day and average of adjusted scores from other sample days. Weights were lowest at start of lactation, highest in midlactation, and intermediate at end of lactation.

Animals↗
PubMed2002

Viability of a five-strain mixture of Listeria monocytogenes in vacuum-sealed packages of frankfurters, commercially prepared with and without 2.0 or 3.0% added potassium lactate, during extended storage at 4 and 100 degrees C.

The viability of Listeria monocytogenes was monitored on frankfurters containing added potassium lactate that were obtained directly from a commercial manufacturer. Eight links (ca. 56 g each) were transferred aseptically from the original vacuum-sealed bulk packages into nylon-polyethylene bags. Each bag then received a 4-ml portion of a five-strain mixture of the pathogen. Frankfurters containing 2.0 or 3.0% potassium lactate were evaluated using 20 CFU per package, and frankfurters containing 3.0% potassium lactate were evaluated using 500 CFU per package. The packages were vacuum-sealed and stored at 4 or 10 degrees C for up to 90 or 60 days, respectively. During storage at 4 degrees C, pathogen numbers remained at about 1.6 log10 CFU per package over 90 days in packages containing frankfurters with 2.0% potassium lactate that were inoculated with about 20 CFU. In packages containing frankfurters with 3.0% potassium lactate that were inoculated with about 20 CFU and stored at 4 degrees C, pathogen numbers remained at about 1.4 log10 CFU per package over 90 days. In packages containing frankfurters with 3.0% potassium lactate that were inoculated with about 500 CFU and stored at 4 degrees C, pathogen numbers remained at about 2.4 log10 CFU per package over 90 days. However, in the absence of any added potassium lactate, pathogen numbers increased to 4.6 and 5.0 log10 CFU per package after 90 days of storage at 4 degrees C for starting levels of 20 and 500 CFU per package, respectively. During storage at 10 degrees C, pathogen numbers remained at about 1.4 log10 CFU per package over 60 days in packages containing frankfurters with 2.0% potassium lactate that were inoculated with about 20 CFU. In packages containing frankfurters with 3.0% potassium lactate that were inoculated with about 20 CFU and stored at 10 degrees C, pathogen numbers remained at about 1.1 log10 CFU per package over 60 days of storage. In the absence of any added potassium lactate, pathogen numbers increased to 6.5 log10 CFU per package after 28 days and then declined to 5.0 log10 CFU per package after 60 days of storage at 10 degrees C. In packages containing frankfurters with 3.0% potassium lactate that were inoculated with about 500 CFU per package, pathogen numbers remained at about 2.4 log10 CFU per package over 60 days of storage at 10 degrees C, whereas in the absence of any added potassium lactate, pathogen numbers increased to about 6.6 log10 CFU per package within 40 days and then declined to about 5.5 log10 CFU per package after 60 days of storage. The viability of L. monocytogenes in frankfurter packages stored at 4 and 10 degrees C was influenced by the pH and the presence or levels of lactate but not by the presence or levels of indigenous lactic acid bacteria or by the proximate composition of the product. These data establish that the addition of 2.0% (P < 0.0004) or 3.0% (P < 0.0001) potassium lactate as an ingredient in frankfurters can appreciably enhance safety by inhibiting or delaying the growth of L. monocytogenes during storage at refrigeration and abuse temperatures.

Animals↗
PubMed2005

High myocardial lactate concentration is associated with poor myocardial function prior to cardiopulmonary bypass.

AIM: This study was designed to analyse the relationship between myocardial lactate--determined by microdialysis--and hemodynamics during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: Twenty consecutive patients with coronary artery disease were enrolled for this prospective, observational study. Microdialysis measurements were performed in the apical region of the heart during periods of 15 to 20 min before, during, and after CPB; hemodynamics and plasma lactate concentrations were determined correspondingly. Correlation analysis revealed a relationship between myocardial lactate concentration and right ventricular ejection fraction at baseline (Spearman's r: 0.6; P=0.02). Patients were thus grouped according to the myocardial lactate concentration at baseline into a high-lactate group (2.5+/-0.7 mmol.l(-1), n=10) and low-lactate group (0.9+/-0.5 mmol.l(-1), n=10). RESULTS: Preoperative left ventricular ejection fraction was not different between the groups (high-lactate group: 53+/-16%; low-lactate group: 57+/-15%; P=n.s.) Patients in the high-lactate-group had a lower stroke volume index (P=0.005) and right ventricular ejection fraction (P=0.04) before, and higher central venous and pulmonary artery pressures (P<0.01) after CPB. Plasma lactate was significantly higher during CPB in the high-lactate-group (P<0.05). No correlation was observed between myocardial and plasma lactate. Six patients in the high-lactate but none in the low-lactate-group needed inotropic support after weaning from CPB (P=0.01). CONCLUSIONS: These data are suggestive of an association between subtle myocardial ischemia--detected by microdialysis--and perioperative myocardial dysfunction in patients undergoing CABG. The microdialysis technique may be a valuable adjunct for monitoring myocardial metabolism during cardiac surgery.

Aged↗
PubMedDate not supplied

Lactate transport and transporters: general principles and functional roles in brain cells.

Lactate is transported across cell membranes by diffusional, saturable cotransport with protons, mediated by monocarboxylate transporters (MCTs). This transport is bidirectional and in the absence of a transcellular H(+) gradient, it can increase the intracellular concentration of lactate up to but not beyond the extracellular level (or vice versa). If extra- and intracellular pH differ, however, the equilibrium level is determined by the gradients of both lactate anions and protons. Rates of lactate uptake are determined most often by measuring uptake of labeled lactate, e.g., [U-14C]lactate. In the case of lactate and other compounds that are metabolized, errors are introduced easily because continuing inwardly directed diffusional net transport of label can be achieved by intracellular metabolism, reducing the intracellular level of the nonmetabolized lactate and thus maintaining a concentration gradient between extra- and intracellular concentrations of the nonmetabolized compound (metabolism-driven uptake). For measurement of facilitated diffusion kinetics, it is essential that the period during which the uptake is measured is short enough that little or no metabolism-driven uptake contributes to the measured uptake (or that first-order regression analysis is carried out to obtain initial uptake rates from nonlinear traces). To achieve initial uptake rates, incubation periods well below 1 min are generally required. Lactate uptake is fast in astrocytes, which express powerful, low-affinity MCTs, i.e., MCT1 and MCT4. Due to the low affinity of these transporters, they respond to increased lactate gradients with enhanced transporter activity. The predominant MCT in neurons is the high-affinity MCT2, which can only increase its activity to a limited extent in the face of an increased lactate gradient. This is reflected by a high-affinity lactate uptake, although most investigators also have demonstrated a component of lactate uptake with lower affinity. In both neurons and astrocytes, however, facilitated diffusion is fast enough that under most conditions lactate fluxes will be determined mainly by the rate of metabolism-driven uptake, and MCT-mediated transport only will be rate-limiting after establishment of large transmembrane gradients.

Animals↗
PubMed2005

Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity.

It is hypothesized that L-lactate derived from astrocyte glycogen sustains axon excitability in mouse optic nerve (MON). This theory was tested by using a competitive antagonist of L-lactate transport and immunocytochemistry to determine whether transport proteins are appropriately distributed in adult MON. L-lactate sustained the compound action potential (CAP), indicating that exogenous L-lactate was an effective energy substrate. During 60 min of aglycemia, the CAP persisted for 30 min, surviving on a glycogen-derived substrate (probably lactate), before failing. After failing, the CAP could be partially rescued by restoring 10 mM glucose or 20 mM L-lactate. Aglycemia in the presence of 20 mM D-lactate, a metabolically inert but transportable monocarboxylate, resulted in accelerated CAP decline compared with aglycemia alone, suggesting that D-lactate blocked the axonal uptake of glycogen-derived L-lactate, speeding the onset of energy failure and loss of the CAP. The CAP was maintained for up to 2 hr when exposed to 20% of normal bath glucose (i.e., 2 mM). To test whether glycogen-derived L-lactate "supplemented" available glucose (2 mM) in supporting metabolism, L-lactate uptake into axons was reduced by the competitive inhibitor D-lactate. Indeed, in the presence of 20 mM D-lactate, the CAP was lost more rapidly in MONs bathed in 2 mM glucose artificial cerebrospinal fluid. Immunocytochemical staining demonstrated cell-specific expression of monocarboxylate transporter (MCT) subtypes, localizing MCT2 predominantly to axons and MCT1 predominantly to astrocytes, supporting the idea that L-lactate is released from astrocytes and taken up by axons as an energy source for sustaining axon excitability.

Action Potentials↗
PubMedDate not supplied

Involvement of brain lactate in neuronal metabolism.

The involvement of brain lactate in neuronal metabolism was analyzed by ex vivo NMR spectroscopy with rats under the effects of pentobarbital, alphachloralose or morphine, which were infused with a solution of either [1-(13)C]glucose+lactate or glucose+[3-(13)C]lactate for 20 min. Electroencephalogram recordings indicated different brain electrical activity levels under the three drugs with a clear distinction between pentobarbital, on the one hand, and alphachloralose and morphine on the other. Labeling of metabolites in brain perchloric acid extracts and of blood glucose and lactate was determined by (13)C- and/or (1)H-observed/(13)C-edited-NMR spectroscopy. The following were found: (i) the ratio between glutamate C3 and C4 (13)C-enrichments increased from pentobarbital to alphachloralose and morphine whatever the labeled precursor, indicating a link between metabolic and electrical activity; (ii) under glucose+[3-(13)C]lactate infusion, alanine C3 and acetyl-CoA C2 enrichments were higher than that of lactate C3, revealing the occurrence of an isotopic dilution of the brain exogenous lactate (arising from blood) by lactate from brain (endogenous lactate); the latter was synthesized from glycolysis in a compartment other than the neurons; (iii) the contributions of labeled glucose and lactate to acetyl-CoA C2 enrichment indicated that the involvement of blood glucose relative to that of blood lactate to brain metabolism was correlated with brain activity. It can therefore be concluded that the brain electrical activity-dependent increase in the contribution of blood glucose relative to that of blood lactate to brain metabolism occurred partly via the increase in the metabolism of lactate generated from astrocytic glycolysis. This conclusion supports the hypothesis of an astrocyte-neuron lactate shuttle component in the coupling mechanism between cerebral activity and energy metabolism.

Animals↗
PubMed2004

Maximal lactate steady state in trained adolescent runners.

The aims of this study were: (1) to identify the exercise intensity that corresponds to the maximal lactate steady state in adolescent endurance-trained runners; (2) to identify any differences between the sexes; and (3) to compare the maximal lactate steady state with commonly cited fixed blood lactate reference parameters. Sixteen boys and nine girls volunteered to participate in the study. They were first tested using a stepwise incremental treadmill protocol to establish the blood lactate profile and peak oxygen uptake (VO2). Running speeds corresponding to fixed whole blood lactate concentrations of 2.0, 2.5 and 4.0 mmol x l(-1) were calculated using linear interpolation. The maximal lactate steady state was determined from four separate 20-min constant-speed treadmill runs. The maximal lactate steady state was defined as the fastest running speed, to the nearest 0.5 km x h(-1), where the change in blood lactate concentration between 10 and 20 min was < 0.5 mmol x l(-1). Although the boys had to run faster than the girls to elicit the maximal lactate steady state (15.7 vs 14.3 km x h(-1), P < 0.01), once the data were expressed relative to percent peak VO2 (85 and 85%, respectively) and percent peak heart rate (92 and 94%, respectively), there were no differences between the sexes (P > 0.05). The running speed and percent peak VO2 at the maximal lactate steady state were not different to those corresponding to the fixed blood lactate concentrations of 2.0 and 2.5 mmol x l(-1) (P > 0.05), but were both lower than those at the 4.0 mmol x l(-1) concentration (P < 0.05). In conclusion, the maximal lactate steady state corresponded to a similar relative exercise intensity as that reported in adult athletes. The running speed, percent peak VO2 and percent peak heart rate at the maximal lactate steady state are approximated by the fixed blood lactate concentration of 2.5 mmol x l(-1) measured during an incremental treadmill test in boys and girls.

Adolescent↗
PubMed1999

Effect of major hepatectomy on glucose and lactate metabolism.

BACKGROUND: The liver plays an important role in glucose and lactate metabolism. Major hepatectomy may therefore be suspected to cause alterations of glucose and lactate homeostasis. METHODS: Thirteen subjects were studied: six patients after major hepatectomy and seven healthy subjects who had fasted overnight. Glucose turnover was measured with 6,6(2)H glucose. Lactate metabolism was assessed using two complementary approaches: 13C-glucose synthesis and 13CO2 production from an exogenous 13C-labeled lactate load infused over 15 minutes were measured, then the plasma lactate concentrations observed over 185 minutes after lactate load were fitted using a biexponential model to calculate lactate clearance, endogenous production, and half-lives. RESULTS: Three to five liver segments were excised. Compared to healthy controls, the following results were observed in the patients: 1) normal endogenous glucose production; 2) unchanged 13C-lactate oxidation and transformation into glucose; 3) similar basal plasma lactate concentration, lactate clearance, and lactate endogenous production; 4) decreased plasma lactate half-life 1 and increased half-life 2. CONCLUSIONS: Glucose and lactate metabolism are well maintained in patients after major hepatectomy, demonstrating a large liver functional reserve. Reduction in the size of normal liver parenchyma does not lead to hyperlactatemia. The use of a pharmacokinetic model, however, allows the detection of subtle alterations of lactate metabolism.

Adult↗
PubMed1997

Effect of continuous venovenous hemofiltration with dialysis on lactate clearance in critically ill patients.

OBJECTIVE: To evaluate the effect of continuous venovenous hemofiltration with dialysis on lactate elimination by critically ill patients. DESIGN: Prospective, clinical study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Ten critically ill patients with acute renal failure and stable blood lactate concentrations. INTERVENTIONS: Two-stage investigation: a) measurement of lactate concentrations in samples of serum and ultradiafiltrate from patients receiving continuous venovenous hemofiltration with dialysis to calculate lactate clearance by the hemofilter; b) evaluation of total plasma lactate clearance by infusing sodium L-lactate (1 mmol/kg of body weight) over 15 mins. MEASUREMENTS AND MAIN RESULTS: Arterial lactate concentration was determined before, during, and after the infusion. Lactate elimination variables were calculated from the plasma curve using model-independent and model-dependent estimates (by software). At the end of the infusion, median blood lactate concentration increased from 1.4 mmol/L (range 0.8 to 2.6) to 4.8 mmol/L (range 2.4 to 5.7) and returned to 1.6 mmol/L (range 0.9 to 3.4) 60 mins later. The median total plasma lactate clearance was 1379 mL/min (range 753.7 to 1880.7) and the median filter lactate clearance was 24.2 mL/min (range 7.1 to 35.6). Thus, filter lactate clearance accounted for < 3% of total lactate clearance. CONCLUSIONS: Continuous venovenous hemofiltration with dialysis cannot mask lactate overproduction, and its blood concentration remains a reliable marker of tissue oxygenation in patients receiving this renal replacement technique.

Acidosis, Lactic↗