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PubMed1994

Preliminary application of magnetic resonance spectroscopy to investigate lactate-induced panic.

OBJECTIVE: To characterize changes associated with lactate-induced panic, proton magnetic resonance spectroscopy (MRS) was used to measure brain lactate during intravenous infusion of 0.5-M sodium lactate in panic disorder patients and comparison subjects. METHOD: Eight panic disorder subjects, five medicated and three unmedicated, and eight healthy comparison subjects were studied at baseline, during lactate infusion (5 meq/kg over 20 minutes), and after infusion. Localized proton MRS was used to acquire averaged spectra every 5 minutes from a 27-ml sampling volume in the insular cortex and adjacent regions. Brain lactate levels, quantitatively estimated in relationship to N-acetyl aspartate, were compared to blood lactate levels. RESULTS: The procedure was generally well tolerated; one panic subject requested early termination before lactate infusion. Significant rises in brain lactate levels occurred for all subjects during infusion. The panic patients who responded to lactate (N = 3) had significantly higher brain lactate levels before, during, and after infusion than did the comparison subjects (N = 8) and medicated patients who were lactate nonresponders (N = 4). After infusion the panic patients with lactate-induced panic exhibited a striking dissociation between decreasing blood lactate and further increases in brain lactate levels. CONCLUSIONS: These preliminary observations indicate that brain lactate increases during a standard lactate infusion. Lactate-induced panic is associated with greater increases than in comparison subjects and with prolonged elevations in brain lactate that are decoupled from falling blood lactate levels after completion of lactate infusion. Further investigation is necessary to clarify the mechanism(s) responsible for these findings and establish whether a causal relationship to the occurrence of lactate-induced panic exists.

Adult↗
PubMed2005

Genetic profile of total body energy content of Holstein cows in the first three lactations.

Weekly total body energy content (TBEC) was calculated for 444 Holstein cows in their first 3 lactations. These calculations were based on body lipid and protein changes predicted from weekly changes in body condition score and live weight of each cow. In first lactation, cows lost TBEC during the initial 8 wk, regained it by wk 22, and continued to build up their reserves until wk 37. Cows started lactations 2 and 3 with considerable reserves from the dry period that they used during the first 13 wk of lactation. Variance components for TBEC were estimated using random regression analysis allowing for heterogeneous residual variance. The genetic variance increased within each lactation, suggesting that the genetic component becomes more important as lactation progresses. The genetic correlations between very early (wk 1 to 4) and later stages of first lactation were near zero but they increased considerably between later lactation stages. Genetic correlations between TBEC on wk 5 of first lactation and the remainder of this lactation ranged from 0.64 for the more distant weeks to 0.99 for the immediately subsequent weeks. Genetic correlations with TBEC in second lactation were moderately high (0.68 to 0.70) for the early weeks (1 to 8) and decreased gradually to 0.56 for weeks at the end of lactation. For third lactation, these estimates ranged from 0.53 to 0.63. Genetic correlation estimates of TBEC in wk 12 of first lactation with subsequent first-lactation weeks varied from 0.79 to 0.99, whereas they ranged from 0.65 to 0.77 and from 0.57 to 0.68 in second and third lactations, respectively. The genetic correlation between TBEC in later weeks of first lactation and the rest of productive life increased as first lactation progressed, but the improvement diminished. Weekly genetic evaluations for first-lactation TBEC were used to predict second- and third-lactation energy content. The accuracy of these predictions increased with progressing weeks in first lactation, but about three-fourths of the improvement occurred by wk 5. Our results suggest that TBEC calculated after a month from the first calving may give useful information about the future energy content of a cow.

Animals↗
PubMed1988

Production and clearance of lactate from brain tissue, cerebrospinal fluid, and serum following experimental brain injury.

Lactate dynamics in the brain, cerebrospinal fluid (CSF), and serum were studied in 20 chloralose-anesthetized cats following fluid-percussion trauma. Brain lactate and brain tissue pH were measured by hydrogen-1 and phophorus-31 magnetic resonance spectroscopy. The CSF, arterial, and cerebrovenous serum lactate levels as well as serum glucose concentration were quantified. In the six sham-operated control animals, brain, CSF, cerebrovenous, and arterial lactate levels as well as brain pH remained at normal values. In the five animals in the mild-trauma group (1.6 atm), brain and CSF lactate levels were moderately elevated, although the brain pH and serum lactate content remained at control values. Severe trauma (3.1 atm) in nine cats produced an 82% increase in the brain lactate index and a reduction in brain tissue pH (7.02 +/- 0.02 to 6.95 +/- 0.02; mean +/- standard error of the mean), indicating brain tissue acidosis caused by excessive lactate accumulation. Brain lactate levels reached a peak 1 1/2 hours after severe trauma, then steadily decreased to normal levels by 8 hours posttrauma. Maximum increases of CSF and arterial lactate levels (from 1.4 +/- 0.2 to 4.1 +/- 0.4 and from 1.6 +/- 0.2 to 4.1 to 0.6 mmol/liter, respectively) were observed 15 minutes after trauma, and the values decreased during the next 2 hours. The response was biphasic, with a secondary rise observed in both CSF and serum lactate levels during the remaining 4 hours of the experiment. The difference between the arterial and venous lactate levels (A-Vlact) gradually increased and reached a peak 2 hours postinjury (from -0.05 +/- 0.10 to -0.41 +/- 0.09 mmol/liter). The results of this study show that the production of lactate in brain tissue, CSF, and blood increased in proportion to the severity of the injury. The observation that lactate levels in blood and CSF are maximum immediately following impact while brain lactate and A-Vlact are gradually increasing suggests that the brain-tissue production of lactate fails to account for the rapid appearance of lactate in CSF and blood. It is speculated that the initial elevation of CSF lactate values reflects the systemic response of trauma, and the secondary rise of CSF lactate levels following severe trauma is due to slow seepage of lactate produced by brain tissue into the CSF space. These studies are the first to describe the temporal profile of brain lactate production and eventual clearance by CSF and blood in fluid-percussion injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Reproductive performance in the subsequent lactation of dairy cows previously treated for failure to be detected in oestrus.

AIM: To describe the effect of treatment of cows not detected in oestrus (NDO) with progesterone (P4) and oestradiol benzoate (ODB) in one lactation, on the reproductive and productive performance in the subsequent lactation. METHODS: Cows (n=770 from nine herds) which were NDO 10 days before the planned start of the seasonal breeding programme (PSM) were blocked by herd, age (2 or >2 years old) and ovarian status (i.e. with or without a palpable corpus luteum; CL), and treated either with an intravaginal progesterone-releasing device and ODB and resynchrony, or were left as untreated controls. In the following lactation, data were collected on the occurrence of endometritis, NDO, breeding dates, pregnancy test results and milk production. The effect of treatment and ovarian status in the previous lactation on the incidence of disease, and the proportions submitted for service, conceived and pregnant in the subsequent lactation were analysed. Calving dates and intervals from start of breeding to first insemination and conception were analysed using Kaplan Meier survival analysis. Additional multivariate analyses were undertaken to include known confounders such as age, breed, herd, calving date and milk production, as well as the cyclic status (i.e. previously cycling, NDO, or "late-calving") in the previous lactation, to examine the potential "carryover" effects of previous status on the reproductive performance in the subsequent lactation. RESULTS: Treatment of NDO cows resulted in an earlier calving date (Julian calving date 214, 95% CI=207-221, vs 224, 95% CI=220-228; p=0.005), more female calves reared (31.4% vs 23.3%; p=0.01), and reduced risk of being NDO (33.9% vs 46.1%; p=0.002) in the subsequent lactation compared with controls. There were no differences in the incidence of peripartum disease, or the proportion of cows submitted, conceived or pregnant between the Treatment and Control groups in the subsequent lactation (p>0.2). Previously CL-positive (+ve) NDO cows were less likely to produce a female calf that was reared (19.0% vs 29.9%; p=0.005), more likely to be treated as NDO (26.4% vs 18.6%; p=0.02), less likely to conceive by the end of the subsequent lactation's breeding programme (82.2% vs 87.8%; p=0.09), and took longer to conceive (41 vs 33 days from the PSM to conception) than cows that were NDO-CL-negative (-ve) in the previous lactation. There was no interaction between ovarian status and treatment for any of the outcome variables (p>0.05). Cows that were NDO or late-calving in the previous lactation were more likely to be NDO (p<0.005), treated as NDO (p<0.005), and have longer PSM to conception intervals (p<0.005) in the subsequent lactation than cycling herdmates, despite inclusion of factors known to confound reproductive performance in analyses. CONCLUSIONS: Treatment of NDO cows resulted in more female calves reared, earlier calving and a reduced risk of being NDO in the subsequent lactation. Status (i.e. NDO-CL+ve or NDO-CL-ve) affected some reproductive measures in the subsequent lactation, and the effect of treatment in the subsequent lactation differed between the two groups for some measures. Reproductive performance in the subsequent lactation was not improved despite the earlier calving date and longer calving to PSM intervals. Additionally, the previous season's status was still important in the subsequent season's reproductive performance, despite adjusting for known confounders of fertility. CLINICAL RELEVANCE: The economic benefits from treatment of NDO cows are likely limited to effects of an earlier calving date and potential for longer lactation and increased milk yield, increased number of calves derived from artificial insemination and from a reduced number of NDO cows in the subsequent lactation. Effects of improved reproductive performance in the subsequent lactation were not demonstrated and hence should not be included in any economic analysis of therapy of NDO cows.

Age Factors↗
PubMed1976

Lactate metabolism in the isolated perfused rat kidney: relations to renal function and gluconeogenesis.

In the intact dog, decreases in both glomerular filtration rate and net renal Na+ reabsorption due to raised ureteral pressure were not associated with a decrease in renal lactate oxidation rate, although total renal CO2 production decreased in proportion to the changes in net renal reabsorption of Na+ and glomerular filtration rate. 2. In order to determine whether, in the absence of other added substrates, the metabolism of lactate supports only the 'basal' renal metabolism or can enhance renal function as well, the rate of lactate utilization and decarboxylation by the isolated perfused rat kidney have been quantified in relation to renal function and one measure of renal basal metabolism, glucose production. 3. The perfusate was Krebs-Ringer bicarbonate (pH 7-35-7-48) with Fraction V bovine serum albumin, 6g/100 ml. L-(+)-lactate was added to raise the lactate concentration from endogenous levels to 2-5, 5-0 or 10 mM. 4. We determined: net lactate utilization rate, lactate decarboxylation rate (14CO2 produced from L-(+)-[U-14C]lactate), net glucose production rate, and net re-absorptive rate of Na+. 5. The apparent Km and Vmax for lactate oxidation were 2-1 mM and 1-29 mumole.g-1.min-1 respectively. There was no apparent maximum for total lactate utilization rate due to continuing increases in glucose production rate as lactate concentration was raised. At ca. 10 mM lactate, glucose production accounted for about half of the total lactate utilized. Therefore the basal energy requirements of the kidney need not be constant since glucose production increases as lactate concentration is raised. 6. Both lactate oxidation rate and lactate utilization rate were significantly correlated with the net reabsorption of Na+ by the renal tubules, with the percentage of filtered Na+ reabsorbed and with the glomerular filtration rate. The major fraction of the net renal reabsorption of Na+ was probably supported by the metabolism of substrates either bound to albumin or derived from renal tissue since the percentage of filtered Na+ reabsorbed increased from ca. 78%, when no lactate was added, to 97% when initial lactate concentration was 10 mM. Therefore, addition of lactate increased both the basal mebabolism and tubular function. However, these observations do not permit us to conclude whether it was the presence of lactate, or its utilization by oxidative or by other pathways which enhanced net renal reabsorption of Na+ and the glomerular filtration rate.

Animals↗
PubMed1994

Lactate transport mechanisms at apical and basolateral membranes of bovine retinal pigment epithelium.

The isolated bovine retinal pigment epithelium actively transports lactate from the apical to the basal bath. Net short-circuit [14C]lactate flux in 20 mM lactate was 0.46 +/- 0.09 mu eq.cm-2.h-1 (n = 8). In open circuit, with a physiological lactate gradient, net [14C]lactate flux was 0.66-1.31 mu eq.cm-2.h-1 (n = 3). Lactate in the apical bath caused intracellular acidifications that were saturable, apparently stereospecific, and reduced in magnitude by several H-lactate cotransport inhibitors. In the basal bath, lactate caused intracellular alkalinizations that were dependent on the presence of Na. In short circuit, 20 mM lactate in both baths reversed the direction of net transepithelial 22Na transport from secretion to absorption, suggesting the presence of basolateral Na-lactate cotransport moving lactate out of the cells. Outwardly directed Na-lactate cotransport requires a lactate:Na stoichiometry > 1.4:1, consistent with the coupled movement of Na, lactate, and net negative charge across the basolateral membrane. Intracellular microelectrode recordings showed that basal lactate hyperpolarized and apical lactate depolarized the basolateral membrane. For lactate absorption, this is a novel arrangement of membrane proteins:luminal H-lactate cotransport and serosal electrogenic Na:(n)lactate cotransport. Lactate transport across the retinal pigment epithelium may play an important role in regulating retinal metabolism and subretinal space volume and composition.

Animals↗
PubMed2001

Limits to sustained energy intake. III. Effects of concurrent pregnancy and lactation in Mus musculus.

To determine whether mice were limited in their capacity to absorb energy during late lactation, we attempted to increase the energy burden experienced by a group of female mice during late lactation by mating them at the postpartum oestrus, hence combining the energy demands of pregnancy and lactation. These experimental mice were therefore concurrently pregnant and lactating in their first lactation, and were followed through a normal second lactation. In a control group, females also underwent two lactations but sequentially, with the second mating after the first litter had been weaned. Maternal mass and food intake were measured throughout the first lactation, second pregnancy and second lactation. Maternal resting metabolic rate (RMR) was measured prior to the first mating and then at the peak of both the first and second lactations. Litter size and litter mass were also measured throughout both lactations. In the first lactation, experimental mice had a lower mass-independent RMR (F1,88=5.15, P=0.026) and raised significantly heavier pups (t=2.77, d.f.=32, P=0.0093) than the control mice. Experimental mice delayed implantation at the start of the second pregnancy. The extent of the delay was positively related to litter size during the first lactation (F1,19=4.58, P=0.046) and negatively related to mean pup mass (F1,19=5.78, P=0.027) in the first lactation. In the second lactation, the experimental mice gave birth to more (t=2.75, d.f.=38, P=0.0092) and lighter (t=-5.01, d.f.=38, P<0.0001) pups than did the controls in their second lactation. Maternal asymptotic daily food intake of control mice in the second lactation was significantly higher (t=-4.39, d.f.=37, P=0.0001) than that of the experimental mice and higher than that of controls during their first lactation. Despite the added burden on the experimental females during their first lactation, there was no increase in their food intake, which suggested that they might be limited by their capacity to absorb energy. However, control females appeared to be capable of increasing their asymptotic food intake beyond the supposed limits estimated previously, suggesting that the previously established limit was not a fixed central limitation on food intake. As RMR increased in parallel with the increase in food intake during the second lactation of control mice, the sustained energy intake remained at around 7.0xRMR.

Animals↗
PubMed2000

Evidence for lactate uptake after rat fluid percussion brain injury.

UNLABELLED: Traumatic brain injury (TBI) places enormous early energy demand on brain tissue to reinstate normal ionic balance. Glucose declines and lactate increases after TBI as demonstrated in clinical and lab studies, suggesting increased glycolysis. This led us to hypothesize that high extracellular fluid (ECF) lactate may be beneficial after TBI. We measured cerebral dialysate lactate and glucose, and arterial lactate and glucose, before & after rat Fluid Percussion Injury (FPI) (2.06 +/- 0.13 atm) with and without i.v. lactate infusion (100 mM x 4.5 hours) to test the hypotheses that arterial lactate determines ECF lactate. 14C-lactate autoradiography was also performed, to demonstrate whether lactate is taken up by traumatized brain. RESULTS: Dialysate lactate was always significantly higher than arterial. After lactate infusion, both the dialysate and the arterial lactate were significantly increased (P < 0.0001). Dialysate lactate increased within 10 min. following FPI, with significantly higher values in the lactate infusion group (82% higher with lactate infusion after FPI). Dialysate glucose fell following FPI, with a more severe decline in the saline group (129% lower), suggesting lactate infusion preserves or "spares" glucose in ECF. In our autoradiographic study, i.v. 14C-lactate accumulated at the injury site, with levels 2-4 times higher than in contralateral cortex. In conclusion, arterial lactate augmentation thus increases brain dialysate lactate and results in less reduction in ECF glucose, after FPI. Infused lactate accumulates at the injury site, where metabolism is probably the greatest.

Animals↗
PubMed2000

Muscle as a consumer of lactate.

Historically, muscle has been viewed primarily as a producer of lactate but is now considered also to be a primary consumer of lactate. Among the most important factors that regulate net lactate uptake and consumption are metabolic rate, blood flow, lactate concentration ([La]), hydrogen ion concentration ([H+]), fiber type, and exercise training. Muscles probably consume more lactate during steady state exercise or contractions because of increased lactate oxidation since enhancements in lactate transport due to acute activity are small. For optimal lactate consumption, blood flow should be adequate to maintain ideal [La] and [H+] gradients from outside to inside muscles. However, it is not clear that greater than normal blood flow will enhance lactate exchange. A widening of the [La] gradient from outside to inside muscle cells along with an increase in muscle [La] enhances both lactate utilization and sarcolemmal lactate transport. Similarly, a significant outside to inside [H+] gradient will stimulate sarcolemmal lactate influx, whereas an increased intramuscular [H+] may stimulate exogenous lactate utilization by inhibiting endogenous lactate production. Oxidative muscle fibers are metabolically suited for lactate oxidation, and they have a greater capacity for sarcolemmal lactate transport than do glycolytic muscle fibers. Endurance training improves muscle capacity for lactate utilization and increases membrane transport of lactate probably via an increase in Type I monocarboxylate transport protein (MCT1) and perhaps other MCT isoforms as well. The future challenge is to understand the regulatory roles of both lactate metabolism and membrane transport of lactate.

Animals↗
PubMed1971

Ethanol-induced hyperlacticacidemia: inhibition of lactate utilization.

The effects of oral ethanol administration on blood glucose and lactate concentrations, lactate inflow and outflow rates, and lactate incorporation into glucose were investigated in eight human volunteers. Lactate incorporation into glucose, lactate turnover, and lactate inflow and outflow rates were determined during an 8 hr constant infusion of 100 muCi of lactate-U-(14)C. Ethanol was administered by mouth at hourly intervals, 60 ml of bonded whiskey initially and 30 ml/hr thereafter. Blood lactate concentrations increased precipitously after the administration of ethanol, reached a plateau within 120-180 min, and remained constant thereafter despite the continued administration of ethanol. Before ethanol, the lactate turnover rate was 0.76 mmoles/kg per hr +/-0.05 (SEM) and lactate inflow and outflow rates were closely balanced. During the administration of ethanol, the lactate inflow rate was unchanged, but the lactate outflow rate was significantly inhibited, decreasing to 50% of the inflow rate. Despite the continued administration of ethanol, equilibrium between lactate inflow and outflow was restored within 120-180 min and coincided temporally with establishment of a constant blood lactate concentration. Lactate oxidation was unaltered by ethanol, but lactate incorporation into glucose was significantly inhibited. Lactate incorporation into glucose was reduced within 30 min of the administration of ethanol, and nadir values were reached within 120-180 min. Lactate incorporation into glucose remained constant thereafter at rates that were only 30% of those observed in the absence of ethanol. The results of these studies indicate that ethanol-induced hyperlacticacidemia is due to decreased lactate disposal rather than increased lactate production.

Adult↗
PubMed1985

Metabolic utilization and renal handling of D-lactate in men.

This study was carried out to investigate the renal handling of d- and l-lactate and the extent of their metabolism in men. Ten healthy male subjects were given an intravenous (IV) infusion of a racemic mixture of d- and l-lactate. At an infusion rate of 1.0 to 1.3 meq/kg body weight of each isomer, d-lactate achieved a concentration in plasma of 1.7 to 3.0 meq/L, and l-lactate 2.8 to 4.2 meq/L. At these levels, fractional excretion of d-lactate ranged from 40% to 65%, while fractional excretion of l-lactate was always less than 5%. At a higher infusion rate, 1.8 to 2.0 meq/kg/h, plasma concentrations of d- and l-lactate reached 4.5 to 6.0 meq/L, and 4.0 to 6.7 meq/L, respectively. Fractional excretion of d-lactate then ranged from 61% to 100%, while that of l-lactate ranged from 9% to 30%. At plasma concentrations of d-lactate less than 3.0 meq/L, reabsorption of l-lactate was nearly complete, but when plasma d-lactate exceeded 3.0 meq/L, reabsorption of l-lactate was considerably impaired. Similarly, for a given concentration of plasma d-lactate, its reabsorption was more efficient when the plasma l-lactate concentration and fractional excretion of l-lactate were low than when they were high. At an infusion rate of d-lactate of 1.0 to 1.3 meq/L, about 90% of the infused lactate was metabolized, and at a higher infusion rate, still more than 75% of the infused lactate was metabolized.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine↗
PubMed1990

Kinetics of lactate transport into rat liver in vivo.

Lactate clearance by liver plays an important role in lactate homeostasis and in the development of lactic acidosis. The role of lactate delivery to liver as a limiting factor in hepatic uptake of lactate is unclear. Lactate delivery of mechanisms could be important if rates of lactate transport approximate rates of lactate metabolism by liver. The rates of lactate transport into liver have been determined in vitro with isolated liver cells and the results have been conflicting. Therefore, the present studies measure the rate of transport of [14C]-L-lactate, and its poorly metabolizeable stereoisomer, [14C]-D-lactate, into rat liver in vivo using a portal vein injection technique. The transport of [3H]-water and of [14C]-sucrose, an extracellular reference compound, were also studied. Portal blood flow was determined from the kinetics of [3H]-water efflux in liver and was 1.93 +/- 0.22 mL/min/g. The volumes of distribution of [14C]-L-lactate, and [14C]-sucrose were 1.31 +/- 0.22, 0.71 +/- 0.07, and 0.22 +/- 0.07 mL/g, respectively. The extraction of unidirectional influx of [14C]-L-lactate and [14C]-D-lactate by rat liver was 93% +/- 10% and 91% +/- 9%, respectively. The rate of lactate transport into rat liver in vivo, 1.8 mumols.min-1.g-1, is approximately twofold greater than the rate of lactate metabolism by rat liver reported in the literature. Therefore, lactate uptake by liver may not be limited by transport under normal conditions. However, conditions such as decreased portal blood flow, which slow lactate delivery to liver by 50% or more, could cause lactate uptake by liver to be limited by transport of circulating lactate.

Animals↗
PubMed2002

Endotoxin-induced hyperlactatemia results from decreased lactate clearance in hemodynamically stable rats.

OBJECTIVE: To determine whether endotoxin-induced hyperlactatemia in hemodynamically stable animals is due to increased lactate production or decreased lactate clearance by measuring lactate turnover rate in the vascular compartment (LTRvc). DESIGN: Prospective, controlled trial. SETTING: Research laboratory in a university hospital. SUBJECTS: Male Sprague-Dawley rats weighing 275-425 g with chronic vascular catheters. INTERVENTIONS: Chronically catheterized rats were treated with 6 microg/kg endotoxin or saline. LTRvc was determined from the specific activity of carbon-14 [14C]lactate in aortic blood during a constant infusion of [14C]lactate into the inferior vena cava. The role of the splanchnic organs in lipopolysaccharide-induced alterations in LTRvc was determined from the splanchnic first-pass clearance of [14C]lactate infused into the superior mesenteric artery and direct measurements of blood lactate concentration gradients across the splanchnic organs. MEASUREMENTS AND MAIN RESULTS: Despite a 260% increase in lactate concentrations after lipopolysaccharide treatment, the specific activity of [14C]lactate and the LTRvc did not change, indicating that lipopolysaccharide-induced hyperlactatemia is caused by decreased lactate clearance from the vascular compartment rather than increased lactate flux into the vascular compartment. In contrast, lactate clearance by the splanchnic system was increased. The specific activity of [14C]lactate in aortic blood decreased 33% after lipopolysaccharide treatment when the [14C]lactate was infused into the superior mesenteric artery, indicating increased first-pass clearance of [14C]lactate by the splanchnic organs. Furthermore, the hepatic venous-aortic concentration gradient of lactate became increasingly negative after lipopolysaccharide treatment, indicating increased vascular extraction of lactate by the splanchnic system (0.07 +/- 0.07 micromol/mL vs. -0.34 +/- 0.14 micromol/mL). CONCLUSIONS: Lipopolysaccharide-induced hyperlactatemia in hemodynamically stable rats is caused by a net decrease in lactate clearance from the vascular compartment despite the fact that the clearance of lactate by the splanchnic system remains intact.

Acidosis, Lactic↗
PubMed1975

Intracellular pH and distribution of weak acids across cell membranes. A study of D- and L-lactate and of DMO in rat diaphragm.

1. The steady-state distribution ratios of D- and L-lactate between fibre water and external fluid were measured in 'intact' rat hemidiaphragm preparations exposed for 2-5 hr to a variety of solutions of normal ionic strength and osmolarity. The studies were designed to minimize the effects, on these distributions, of conversion of lactate and of generation of lactic acid by the muscle. 2. At D-lactate concentrations between 2.3 and 118 mM, at normal pH and PCO2, the D-lactate distribution ratio, obtained from the distribution of [2-(3)H]D-lactate was independent of concentration; it averaged 0.349. As the concentration of D-lactate was reduced below 2.3 mM, its distribution ratio progressively fell to less than 0.1. 3. Radiochromatograms of extracts of incubated muscle showed that the tritium label was not attached to substances other than lactate. 4. At L-lactate concentrations of 59 and 108 mM, at normal pH and PCO2, the average L-lactate distribution ratios, obtained by enzymatic analysis, were respectively 0.395 and 0392. 5. At 19-89 mM D-lactate, depolarizing the muscle fibres by high K(49-127 mM), at normal pH, PCO2, and [K]0[Cl]0 product, only slightly affected the D-lactate distribution ratio which averaged 0.405. 6. The D-lactate distribution ratio and intracellular pH (pHi), obtained with the DMO method (5,5-dimethyl-2,4-oxazolidinedione), were measured in thirty sets of studies after exposure of the muscle to solutions buffered to pH values ranging between 5.99 and 8.13, and containing 18.5-118 mM D-lactate and 6-129 mM-K. 7. The relation between the distribution ratios of D-lactate ([TL]i/[TL]O) and of H ions ([Ho/[H]i) in these studies could be expressed by [TL]i/[T]O = 0.646 [H]o/[H]i+0.056. 8. It was concluded that it is predominantly the undissociated lactic acid molecules, rather than the much more numerous lactate ions, which permeate the fibre membrane; and that the steady-state lactate distribution ratio is determined by the transmembrane pH gradient, and not by membrane potential. 9. The expression of the steady-state lactate distribution ratio as function of relative membrane permeabilities of lactic acid molecule and lactate ion, membrane voltage, and internal and external H ion concentrations indicates that a finite permeability to the ion, three or four orders of magnitude less than that to the molecule, is compatible with the experimental data. When both ion and molecule of any weak acid are permeable, they act as a carrier system for the movement of protons down their electrochemical gradient. 10. Near-maintenance of pHi in the face of high fibre D-lactate (19-44 mM) and DMO (8-42 mM) indicates stimulation of proton extrusion by acid loans. 11. This extrusion is insensitive to ouabain, as judged from the lack of effect of the drug of pHi with acid loading.

Animals↗
PubMed1997

Release of lactate by the lung in acute lung injury.

UNLABELLED: The pathogenesis of hyperlactatemia during sepsis is poorly understood. We have previously described an increase in lactate concentration across the lung in the dog during early endotoxemia. Accordingly, we sought to determine if the lung releases lactate in humans and what relation this has with lung injury. METHODS: We measured lactate concentrations across the lung and lung injury scores (LIS) in two groups of patients. Group 1 consisted of nine patients with acute lung injury (LIS > or = 2.0) and elevated lactate concentrations (> 2.0 mmol/L). Group 2 contained 12 patients with no acute lung injury (LIS scores < or = 1.5), with or without increased lactate concentrations. Simultaneous measurements of plasma lactate and blood gases were obtained from indwelling arterial and pulmonary artery catheters. Measurements of cardiac output were also obtained. Lactate measurements were done using a lactate analyzer (YSI; Yellow Springs, Ohio). RESULTS: For each patient with acute lung injury and hyperlactatemia, an arterial-venous lactate gradient existed demonstrating release of lactate by the lung. This gradient persisted after correction for changes in hemoconcentration across the lung. The lactate gradient across the lung was 0.4 +/- 0.2 mmol/L for group 1 vs 0.05 +/- 0.1 mmol/L for group 2 (p = 0.001). This corresponded to a mean pulmonary lactate flux of 231.3 +/- 211.3 vs 5.0 +/- 37.2 mmol/h (p = 0.001). The lactate flux and the arterial-venous lactate difference correlated with LIS both for the entire sample and for the subgroup with hyperlactatemia (r = 0.69, p < 0.01). Pulmonary lactate flux was not related to arterial lactate levels (r = 0.25). CONCLUSION: In patients with acute lung injury and hyperlactatemia, the lung is a major source of lactate and lactate flux correlates with LIS. This lactate flux could explain some of the hyperlactatemia seen in sepsis.

Adult↗
PubMed1999

Myocardial lactate metabolism in fetal and newborn lambs.

BACKGROUND: Around birth, myocardial substrate supply changes from carbohydrates before birth to primarily fatty acids after birth. Parallel to these changes, the myocardium is expected to switch from the use of primarily lactate before birth to fatty acids thereafter. However, myocardial lactate uptake and oxidation around birth has not been measured in vivo. METHODS AND RESULTS: We measured myocardial lactate uptake, oxidation, and release with infusion of [1-13C]lactate and myocardial flux of fatty acids and glucose in chronically instrumented fetal and newborn (1 to 15 days) lambs. Myocardial lactate oxidation was the same in newborn (81.7+/-14.7 micromol. min-1. 100 g-1, n=11) as in fetal lambs (60.7+/-26.7 micromol. min-1. 100 g-1, n=7). Lactate uptake was also the same in newborn as in fetal lambs. Lactate uptake was higher than lactate flux, indicating lactate release simultaneously with uptake. In the newborn lambs, lactate uptake declined with age. Lactate uptake was strongly related to lactate supply, whereas lactate oxidation was not. The supply of fatty acids or glucose did not interfere with lactate uptake, but the flux of fatty acids was inversely related to lactate oxidation. CONCLUSIONS: We show that lactate is an important energy source for the myocardium before birth as well as in the first 2 weeks after birth in lambs. We also show that there is release of lactate by the myocardium simultaneously with uptake of lactate. Furthermore, we show that lactate oxidation may be attenuated by fatty acids but not by glucose, probably at the level of pyruvate dehydrogenase.

Aging↗
PubMed1971

Glucose-lactate interrelationships: effect of ethanol.

The effect of ethanol on the interrelationship of lactate and glucose metabolism was investigated in eight human volunteers. Lactate and glucose kinetics and intervconversion rates were determined by the sequential administration of L-(+) lactate-U-(14)C and glucose-1-(14)C over an 8 hr period. After a 12 hr fast, the glucose turnover and recycling rates were 94.0 +/-3.8 (SEM) and 13.7 +/-1.1 mg/kg per hr, respectively. Approximately 50% of the glucose turnover or 40.7 +/-2.1 mg/kg per hr was converted to lactate, accounting for 50% of the lactate turnover rate. Lactate turnover and lactate conversion to glucose were 81.8 +/-6.2 and 16.7 +/-1.1 mg/kg per hr, respectively. Approximately 20% of the glucose turnover was derived from lactate under these conditions. During the administration of ethanol, the blood lactate concentration doubled and the lactate turnover rate declined slightly. Lactate conversion to glucose was markedly inhibited, decreasing from 16 to 5 mg/kg per hr, and the per cent of the glucose turnover derived from lactate decreased from 18 to 6. Despite the marked inhibition of lactate conversion to glucose, neither the blood glucose concentration nor the glucose turnover rate changed. Both glucose recycling and glucose conversion to lactate were decreased, indicating that ethanol inhibited peripheral glucose utilization. There was no difference in the degree of inhibition of lactate incorporation into glucose produced by ethanol when nonfasted subjects were compared with two subjects who had fasted for 48-72 hr despite the presence of hypoglycemia in the latter. These results indicate that starvation is not a prerequisite for ethanol inhibition of gluconeogenesis from lactate in humans but is necessary for the development of hypoglycemia. Inhibition of lactate incorporation into glucose in nonfasted subjects is probably masked by a concomitant increase in glycogenolysis which prevents hypoglycemia. Ethanol decreases glucose conversion to lactate as well as lactate conversion to glucose, thus inhibiting the Cori cycle.

Adult↗
PubMed1999

Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic.

BACKGROUND: A fast, proton echo-planar spectroscopic imaging (PEPSI) technique, capable of simultaneously measuring metabolites from multiple brain regions, was used to investigate the anatomical distribution and magnitude of brain lactate responses to intravenous lactate infusion among subjects with panic disorder and control subjects. METHODS: Fifteen subjects with panic disorder and 10 control subjects were studied. All subjects were medication free and met DSM-IV criteria for panic disorder, or, for controls, no Axis I psychiatric disorder. Two-dimensional axial metabolite images having 1-cm3 spatial resolution were acquired at 61/2-minute intervals during 3 conditions: a 20-minute baseline, 20-minute 0.5-mol/L sodium lactate infusion, and 15-minute postinfusion period. RESULTS: Intravenous lactate infusion increased brain lactate levels throughout the axial brain section studied in all subjects. Panic-disordered subjects had significantly greater global brain lactate increases in response to lactate infusion. Lateralization of brain lactate response did not occur, nor were discrete regional loci of elevated lactate observed. Cerebrospinal fluid lactate changes corresponded to lactate changes in brain tissue. Severity of symptoms provoked by lactate infusion did not directly correlate with brain lactate response. CONCLUSIONS: Greater overall rises in brain lactate among subjects with panic disorder compared with controls occurred in response to lactate infusion. We were unable to detect a distinct regional pattern for magnitude differences in brain lactate rise by which to identify a specific neuroanatomical substrate underlying a lactate-induced panic response. The wide anatomical distribution of these brain lactate increases suggest metabolic and/or neurovascular mechanisms for the abnormal rise in subjects with panic disorder.

Adult↗