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PubMed1994

Cerebral lactate-oxygen index in acute brain injury with acute anemia: assessment of false versus true ischemia.

OBJECTIVE: To evaluate the occurrence of global cerebral ischemia in acute brain trauma with acute anemia by combined measurements of cerebral hemodynamics, oxygenation, and lactate production. DESIGN: Prospective, intervention study. SETTING: Neuroscience intensive care unit of a university hospital. PATIENTS: Adults (n = 22) with severe acute brain trauma (Glasgow Coma Scores ranging from 4 to 8), undergoing frequent serial measurements of total hemoglobin content, jugular oxyhemoglobin saturation, arteriojugular oxygen content difference, arteriojugular lactate concentration difference, lactate-oxygen index, and cerebral blood flow, along with other routine procedures. MEASUREMENTS AND MAIN RESULTS: Acute anemia (disclosed by a total hemoglobin content of < 11 g/dL in at least three measurements) was found in 19 (86%) of 22 patients. In 211 serial multivariate physiologic observations, only one (0.4%) disclosed abnormally negative arteriojugular lactate difference consistent with global cerebral ischemia. However, in 18 (8.5%) studies in seven (31.8%) patients, acute anemia resulted in markedly decreased values of arteriojugular oxygen content difference. The latter, in turn, yielded abnormally high values of lactate-oxygen index despite normal cerebral lactate production (arteriojugular lactate difference) and oxygenation (jugular oxyhemoglobin saturation). CONCLUSIONS: In acute brain injury with acute anemia, global cerebral ischemia is a rare finding. However, false cerebral ischemia may be frequently found, if assessed by the lactate-oxygen index, because the denominator of the index (the arteriojugular oxygen content difference) frequently decreases as a function of decreasing hemoglobin, thus yielding false calculated ischemic high values for lactate-oxygen index despite normal cerebral oxygenation and lactate production.

Acute Disease↗

PubMed1994

Measurement of lactate in acutely ischemic rat kidneys using magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: Quantification of lactate in the kidney by 1H magnetic resonance spectroscopy (MRS) is a difficult task because of the presence of large amounts of peri-renal fat. When an editing scheme is used to detect lactate that filters out all resonances except lactate, there is no suitable metabolite to serve as an internal standard. In this study, the authors evaluate the potential of MRS to measure the absolute lactate concentration in rat kidneys during acute ischemia using MRS. MATERIALS AND METHODS: The authors propose a method based on a double resonance lactate editing scheme used in combination with the fully relaxed water peak as an internal standard. Experiments were performed on the left kidney rendered ischemic in eight rats. RESULTS: Renal lactate concentrations measured by MRS were compared with values derived from chemical analysis. The mean (+/- standard deviation) renal lactate concentrations measured by MRS and determined chemically were 12 +/- 1.2 umol/g, and 12.94 +/- 1.07 umol/g wet weight, respectively. The coefficient of variation for paired observations was 2.96%, indicating excellent agreement between the two methods used for measuring lactate. DISCUSSION: The study results demonstrate that it is possible to assess the lactate concentration in a rat model of ischemic kidney with MRS and suggest that the total lactate pool is detectable by this method under these experimental conditions.

Animals↗

PubMed1996

Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain.

In vertebrates, the interconversion of lactate and pyruvate is catalyzed by the enzyme lactate dehydrogenase. Two distinct subunits combine to form the five tetrameric isoenzymes of lactate dehydrogenase. The LDH-5 subunit (muscle type) has higher maximal velocity (Vmax) and is present in glycolytic tissues, favoring the formation of lactate from pyruvate. The LDH-1 subunit (heart type) is inhibited by pyruvate and therefore preferentially drives the reaction toward the production of pyruvate. There is mounting evidence indicating that during activation the brain resorts to the transient glycolytic processing of glucose. Indeed, transient lactate formation during physiological stimulation has been shown by 1H-magnetic resonance spectroscopy. However, since whole-brain arteriovenous studies under basal conditions indicate a virtually complete oxidation of glucose, the vast proportion of the lactate transiently formed during activation is likely to be oxidized. These in vivo data suggest that lactate may be formed in certain cells and oxidized in others. We therefore set out to determine whether the two isoforms of lactate dehydrogenase are localized to selective cell types in the human brain. We report here the production and characterization of two rat antisera, specific for the LDH-5 and LDH-1 subunits of lactate dehydrogenase, respectively. Immunohistochemical, immunodot, and western-blot analyses show that these antisera specifically recognize their homologous antigens. Immunohistochemistry on 10 control cases demonstrated a differential cellular distribution between both subunits in the hippocampus and occipital cortex: neurons are exclusively stained with the anti-LDH1 subunit while astrocytes are stained by both antibodies. These observations support the notion of a regulated lactate flux between astrocytes and neurons.

Adolescent↗

PubMed1990

Influence of exogenous estradiol on the concentration of antitrypsin, albumin, N-acetyl-beta-D-glucosaminidase and somatic cells in milk of cows at various lactation stages.

Estradiol benzoate (0.02 mg/kg of body weight) was injected (i.m.) daily to 13 ovariectomized cows in their first or third lactations during early (60-90 days), mid (140-200 days) and late (240-300 days) lactation. The majority of the udder quarters were free of bacteria throughout the experiment. Signs of clinical mastitis were observed after 9-19 days of treatment in cows at mid and late lactation. This was accompanied by a decrease in milk yield, an increase in milk somatic cell count (MSCC) and increases in milk concentration of antitrypsin and serum albumin (as indicator of increased permeability); and milk NAGase activity (as indicator of epithelial cell damage or release of the enzyme from phagocytes). NAGase activity was first to increase and on some occasions was not accompanied by an increased MSCC. The response was either absent (first lactation) or relatively mild (third lactation) in cows at the early stages of lactation. The intensity of the inflammatory response increased with advancing lactation stage. Generally, the response of cows in the third lactation was greater than that of cows in the first lactation at a corresponding stage of lactation. Three cows which received the control treatment with vehicle alone showed no changes in any of the parameters except a slight decrease in antitrypsin. All inflammatory indicators correlated negatively with quarter milk production; milk NAGase activity was superior in this respect (r = -0.75). All correlation coefficients were generally higher after, rather than before the hormone treatment.

Acetylglucosaminidase↗

PubMed2005

Ovum pick-up in cycling and lactating postpartum swamp buffaloes (Bubalis bubalis).

The objective of this study was to evaluate the efficiency of Ovum Pick Up (OPU) in cycling (n = 5) and lactating, postpartum, swamp buffaloes (n = 6) with and without gonadotropin stimulation. The OPU was performed every two weeks in all groups of animals, for a total of six sessions. Thirty collections were performed in five cycling buffaloes and 36 collections in six lactating postpartum buffaloes. Buffaloes that received hormonal stimulation were given a total of 400 mg, follicle stimulating hormone (FSH), administered twice daily over 3 days in decreasing doses, together with 100 microg of GnRH, 24 h after the last FSH injection. Following a resting period of 1 month, the two groups of buffaloes, were subjected to the same OPU regimen, but without any hormonal treatment for an additional six OPU sessions. The number of aspirated follicles recorded from the hormonal stimulated, cycling animals and lactating, postpartum buffaloes was not significantly different, 7.2 +/- 3.7 and 9.0 +/- 3.2, respectively (p > 0.05). Recovered oocytes collected from the two groups of hormonally stimulated animals were also not statistically different: 3.7 +/- 2.7 in the cycling and 5.9 +/- 3.5 in the lactating postpartum group (p > 0.05). In the two groups of buffaloes not receiving hormonal stimulation, the number of aspirated follicles was not significantly different: 2.1 +/- 1.4 and 1.4 +/- 0.7 in cycling and lactating postpartum buffaloes respectively (p > 0.05). Recovered oocytes in the non-treated groups were also similar: 1.4 +/- 1.3 vs 0.7 +/- 0.8 in cycling and lactating buffaloes (p > 0.05). Among stimulated buffaloes, most aspirated follicles were small in size (< or =5 mm), whereas they were mostly medium and large sizes in the non-treated buffaloes. The oocyte recovery rate in both the groups, cycling and lactating postpartum, were 51.6% and 69.5% in stimulated groups and 55.0% and 53.1% in non-stimulated groups (p > 0.05). The majority of recovered oocytes were single- and multi-layered, and the number was greater in the cycling than in the lactating, postpartum buffaloes. The number and quality of recovered oocytes was similar in all groups of buffaloes whether they were received or did not receive hormonal stimulation. Moreover no difference was found in multi- and single-layered oocytes between cycling and lactating, postpartum buffaloes. In conclusion, OPU can be performed successfully in swamp buffalo in different reproductive status and FSH administration was shown to increase the number of aspirated oocytes in both cycling and lactating, postpartum buffaloes.

Animals↗

PubMed1992

Metabolism of lactate in the rat brain during the early neonatal period.

The metabolism of lactate in isolated cells from early neonatal rat brain has been studied. In these circumstances, lactate was mainly oxidized to CO2, although a significant portion was incorporated into lipids (78% sterols, 4% phosphatidylcholine, 2% phosphatidylethanolamine, and 1% phosphatidylserine). The rate of lactate incorporation into CO2 and lipids was higher than those found for glucose and 3-hydroxybutyrate. Lactate strongly inhibited glucose oxidation through the pyruvate dehydrogenase-catalyzed reaction and the tricarboxylic acid cycle while scarcely affecting glucose utilization by the pentose phosphate pathway. Lipogenesis from glucose was strongly inhibited by lactate without relevant changes in the rate of glycerol phosphate synthesis. These results suggest that lactate inhibits glucose utilization at the level of the pyruvate dehydrogenase-catalyzed reaction, which may be a mechanism to spare glucose for glycerol and NADPH synthesis. The effect of 3-hydroxybutyrate inhibiting lactate utilization only at high concentrations of 3-hydroxybutyrate suggests that before ketogenesis becomes active, lactate may be the major fuel for the neonatal brain. (-)-Hydroxycitrate and aminooxyacetate markedly inhibited lipogenesis from lactate, suggesting that the transfer of lactate carbons through the mitochondrial membrane is accomplished by the translocation of both citrate and N-acetylaspartate.

3-Hydroxybutyric Acid↗

PubMed1993

Supersensitivity to beta-adrenoceptor stimulation evoked in cultured neonatal rat heart myocytes by L(+)-lactate and pyruvate.

1. Cells from the ventricles of newborn rats were cultured for 8 days in flasks attached to a rocker apparatus to ensure an adequate oxygen supply. 2. The rocked cultures, which had previously been found to be low in lactate and subsensitive to the positive chronotropic action of the beta-adrenergic agonist isoprenaline (ISO; EC50 of (+/-)-ISO around 7 x 10(-7) M), became resensitized and even highly supersensitive to the catecholamine upon treatment with 3 mM L(+)-lactate or 1 mM pyruvate. 3. The resulting concentration-response curves were anomalous in that they extended over 8 log units, with a threshold at about 10(-13) M, but with little or no change in the height and the position of the maximum (at 10(-5) M). The EC50 values and 95% confidence intervals were 2.4 (1.9-3.0) and 5.4 (4.9-6.0) x 10(-11) M, respectively, for the lactate- and pyruvate-induced components of the chronotropic response to (+/-)-ISO. 4. The supersensitive portion of the ISO concentration-response curve was abolished by (-)-propranolol (10(-6) M), indicating that it was due to beta-adrenoceptor stimulation. 5. The cultured heart cells had to be incubated with L(+)-lactate or pyruvate for a minimum of 45 min before an increase in sensitivity to ISO became apparent. This latency was not due to a requirement for protein synthesis. 6. The adenosine-3',5'-monophosphate (cAMP) response to ISO was not noticeably altered by lactate, but (+/-)-ISO, which at 10(-8) M had no effect on the activation state of cAMP-dependent protein kinase (PKA), caused a significant increase in the activity of the enzyme following a 2-h exposure of the cells to 3 mM L(+)-lactate. 7. alpha-cyanocinnamate, an inhibitor of transmembrane transport of lactate and pyruvate, severely inhibited the utilization of L-[U-14C] lactate by the cultured cells at a concentration (5 microM) that eliminated the lactate-evoked potentiation of the chronotropic action of ISO without significantly affecting its unpotentiated action. 8. The beat-accelerating action of the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX) and the lipophilic N6,2'-O-dibutyryl derivative of cAMP (dbcAMP), both of which are capable of elevating myocardial cAMP levels, was not potentiated by 1 mM pyruvate. 9. The question is raised, whether accumulation of lactate, a biochemical hallmark of anaerobiosis, might be a factor in some of the catecholamine-triggered events occurring in acute myocardial ischaemia and infarction.

1-Methyl-3-isobutylxanthine↗

PubMed1982

Effects of water deprivation and hyperhydration in pregnant and lactating goats.

The response to 30 h water deprivation was studied in 7 goats during the last month of pregnancy and during lactation with anestrus as the control period. Plasma osmolality and plasma Na concentration increased by about 4% in pregnant and lactating goats and by about 2% in anestral goats. Plasma AVP concentration rose by about 7 pg/ml in pregnant and lactating goats, but only by about 3 pg/ml during anestrus. PRA was elevated in pregnant animals, but dehydration caused only a minor further rise. Total plasma protein concentration was low in pregnant goats and did not increase during water deprivation, but it did so in lactating animals. Neither the hematocrit nor the plasma K concentration changed in response to dehydration. GFR fell by about 24% in pregnant goats and by 22% in lactating animals, but remained unchanged during anestrus. ERPF fell by 20% in lactating animals, but no consistent effect of the dehydration was seen during pregnancy and anestrus. Urine flow decreased by about 75% during pregnancy, 55% during lactation and 65% during anestrus with the highest urine osmolality observed during anestrus. Milk production was only slightly reduced, but the milk osmolality increased in parallel with that of the blood plasma. When allowed to drink at the end of the water deprivation period, pregnant goats immediately drank 2.5 +/- 0.5 litres, lactating goats 3.3 +/- 0.9 litres and anestral goats 1.1 +/- 0.3 litres. When hyperhydrated, pregnant goats excreted the excessive water more readily and showed less response to exogenous AVP than lactating and anestral animals. In conclusion, pregnant and lactating goats are obviously more susceptible to a shortage of water supply than anestral animals but can easily excrete an excess of water.

Animals↗

PubMed1993

Glycogen breakdown and lactate accumulation during high-intensity cycling.

High-intensity exercise results in a large breakdown of glycogen. The glycogen lost may reappear as hexose phosphates, lactate, or it may be fully oxidized. Part of the lactate produced may be transferred from muscle to blood. There is, however, incomplete information on the relative importance of each endpoint of glycogen breakdown during high intensity exercise. Therefore, 16 healthy men cycled for between 30 s and 3 min until exhaustion. Muscle biopsies were taken from m. vastus lateralis before and immediately after exercise and analysed for glycogen, glucose, glucose-6-phosphate and lactate. In addition the blood lactate concentration was measured at exhaustion, and the O2 uptake was measured throughout the exercise for calculation of glycogen oxidation. The muscle glycogen concentration fell by 17-24 mmol kg-1 wet wt muscle, the muscle glucose and G-6-P concentrations rose by 1 and 4 mmol kg-1 respectively, and the muscle lactate concentration rose by 20-30 mmol kg-1. The blood lactate concentration at exhaustion was 4-9 mmol l-1 above pre-exercise value. Consequently, 60% of the glycogen lost reappeared as lactate within the working muscle, another 20-25% was found as other glycolytic intermediates, 4-13% of the glycogen loss could be accounted for by oxidation. Lactate released to blood could account for approximately 10% of all lactate produced. Therefore, when large muscles are heavily engaged, as during high intensity cycling, most of the glycogen broken down appears as lactate within the working muscle.

Adult↗

PubMed2006

The influence of intracellular lactate and H+ on cell volume in amphibian skeletal muscle.

The combined effects of intracellular lactate and proton accumulation on cell volume, Vc, were investigated in resting Rana temporaria striated muscle fibres. Intracellular lactate and H+ concentrations were simultaneously increased by exposing resting muscle fibres to extracellular solutions that contained 20-80 mm sodium lactate. Cellular H+ and lactate entry was confirmed using pH-sensitive electrodes and 1H-NMR, respectively, and effects on Vc were measured using confocal microscope xz-scanning. Exposure to extracellular lactate up to 80 mm produced significant changes in pH and intracellular lactate (from a pH of 7.24 +/- 0.03, n = 8, and 4.65 +/- 1.07 mm, n = 6, respectively, in control fibres, to 6.59 +/- 0.03, n = 4, and 26.41 +/- 0.92 mm, n = 3, respectively) that were comparable to those observed following fatiguing stimulation (6.30-6.70 and 18.04 +/- 1.78 mm, n = 6, respectively). Yet, the increase in intracellular osmolarity expected from such an increase in intracellular lactate did not significantly alter Vc. Simulation of these experimental results, modified from the charge difference model of Fraser & Huang, demonstrated that such experimental manoeuvres produced changes in intracellular [H+] and [lactate] comparable to those observed during muscle fatigue, and accounted for this paradoxical conservation of Vc through balancing negative osmotic effects resulting from the net cation efflux that would follow a titration of intracellular membrane-impermeant anions by the intracellular accumulation of protons. It demonstrated that with established physiological values for intracellular buffering capacity and the permeability ratio of lactic acid and anionic lactate, P(LacH): P(Lac-), this would provide a mechanism that precisely balanced any effect on cell volume resulting from lactate accumulation during exercise.

Animals↗

PubMed1985

Lactate metabolism by pediococci isolated from cheese.

Pediococcus pentosaceus is commonly found among the adventitious microflora of Cheddar cheese. When this organism was incubated with L-(+)-lactate under anaerobic conditions, L-(+)-lactate was rapidly converted to D-(-)-lactate until racemic (DL) lactate was present. Under aerobic conditions this initial reaction was followed by a slower reaction resulting in the use of both lactate isomers and in the production of acetate and CO2. With intact cells the lactate oxidation system had an optimum pH of 5 to 6, depending on the initial lactate concentration. Cells grown anaerobically possessed lactate-oxidizing activity which increased two- to fourfold as sugar was exhausted from the medium. Aerobic growth further increased specific activities. Cheddar cheese was made with the deliberate addition of P. pentosaceus. When the resulting cheese was grated to expose a large surface area to O2, lactate was converted to acetate at a rate which depended on the density of pediococci in the cheese. The lactate oxidation system remained active in cheese which had been ripened for 6 months.

Acetates↗

PubMed1968

In vitro lactate metabolism by ruminal ingesta.

Ruminal ingesta (300 ml) obtained from a fistulated cow fed alfalfa hay (H), 3.6 kg of grain mixture with corn silage fed ad libitum (S), 2.5:1 grain-alfalfa hay mixture (G), or a 2.5:1 grain-alfalfa hay mixture providing 545 g of sodium and calcium lactate daily (L) were incubated for 8 hr with nonpolymerized sodium lactate or 17% polymerized lactic acid neutralized to pH 6.7. Polymerization had no effect on the rate of lactate utilization. The initial rates of lactate metabolism for the H, G, S, and L ingesta were 0.72, 0.95, 1.8, and 3.4 meq per 100 ml of rumen fluid per hr, respectively. Lactate-2-(14)C was incubated for 4 hr with each type of ruminal ingesta. Of the label recovered in the volatile fatty acids (VFA), 74.1, 61.2, 49.3, and 38.9% was recovered in acetate, and 9.4, 19.8, 23.3, and 51.9% was recovered in propionate with H, G, S, and L ingesta, respectively. The balance of label was distributed between butyrate and valerate. The titratable VFA did not follow this pattern of production. With the hay ingesta, lactate metabolism resulted in a net loss of acetate and a large increase in butyrate. Little propionate was produced. The G, S, and L ingesta metabolized lactate to yield progressively more propionate and less butyrate. Evidence was gathered to suggest that acetate was the primary end product of lactate metabolism but that oxidation of lactate to pyruvate dictated the synthesis of butyrate from acetate to maintain an oxidation-reduction balance. It was noted that acetate and butyrate production from lactate was pH-dependent, with acetate production maximal at pH 7.4 and butyrate at 6.2. Propionate production was largely unaffected within this pH range.

Acetates↗

PubMed1986

Improved myocardial lactate extraction after propranolol in coronary artery disease: effected by peripheral glutamate and free fatty acid metabolism.

Ten patients with chronic effort angina and coronary artery disease (luminal diameter reduction greater than 75%) were stressed by atrial pacing (140 beats/minutes) before and 15 minutes after intravenous propranolol (mean dose 7.4 mg). Myocardial substrate exchange of oxygen, blood lactate, plasma free fatty acids, citrate, glucose, glutamate, and alanine as well as coronary sinus blood flow were measured. Coronary sinus blood flow, oxygen consumption, and systemic haemodynamics did not change after propranolol. Propranolol did not influence arterial lactate concentration, and it reduced the arterial concentration of free fatty acid by 37% and increased that of glutamate by 21%. During pacing myocardial lactate extraction increased in all 10 patients; in two lactate release was converted to lactate uptake. Propranolol reduced free fatty acid uptake and increased glutamate uptake during pacing. For both substances the changes in aortocoronary sinus differences or in uptake or both correlated positively with the changes in their delivery to the heart from extracardial sources (arterial concentrations/loads). In the unstressed state before pacing, aortocoronary sinus lactate differences correlated inversely with free fatty acid differences and positively with those of glutamate. During pacing the relation between lactate and glutamate differences remained positive while the inverse correlation between lactate and free fatty acid differences was lost. Myocardial citrate release was halved during pacing and recovery. Propranolol did not influence alanine or glucose exchanges. An improved myocardial lactate extraction after propranolol administration may be secondary to decreased free fatty acid uptake or increased glutamate uptake or both. In the unstressed state both mechanisms may be of importance. During pacing induced ischaemia, increased glutamate uptake is more likely than reduced free fatty acid uptake to be the mechanism responsible for the improvement in myocardial lactate extraction. The propranolol mediated alterations in myocardial substrate exchanges may reflect the extracardial effects of the drug.

Adult↗

PubMed2026

Exogenous lactate ameliorates Aβ-induced energy deficit and neurotoxicity with increased mitochondrial TCA cycle carbon flux in SH-SY5Y cells.

A growing body of evidence has demonstrated the existence of metabolic dysfunction in neurodegenerative diseases, including Alzheimer's disease (AD), suggesting that deprivation of energy substrates impairs cellular dynamics. As glucose utilization declines in patients with AD, the need for alternative energy sources becomes crucial to sustain neuronal activities and prevent cell death induced by neurotoxic proteins, such as amyloid beta (Aβ) aggregates. In this context, lactate has been investigated as a potential alternative brain energy substrate in several studies, yet its impact on neuronal cells under Aβ-induced toxicity remains unclear. We confirmed significant suppression of energy production-related biological pathways by analyzing brain transcriptomic data of patients with AD. In subsequent in vitro studies, exogenous lactate treatment ameliorated neuron-like cell death caused by Aβ aggregates. Using a 13C stable isotope tracer, we verified cellular lactate uptake and its incorporation into tricarboxylic acid (TCA) cycle in neurons under the neurotoxic condition. 13C metabolic flux analysis further supported these findings by revealing that lactate treatment restored Aβ-suppressed mitochondrial TCA cycle fluxes. These metabolic improvements were accompanied by increased expression of mitochondrial proteins. These findings support lactate shuttling as a mechanism for supplying lactate-derived carbon to mitochondrial energy metabolism, which may improve neuronal resilience under Aβ-induced metabolic stress.NEW & NOTEWORTHY This study shows that lactate treatment attenuates Aβ-induced cell death in neuron-like cells and supports mitochondrial carbon metabolism. Glycolytic hypometabolism was observed in human AD brain transcriptome and Aβ-treated neuron-like cells. We confirmed that lactate replenished mitochondrial energetics, making neurons more resilient to neurotoxicity. Using 13C tracing and metabolic flux analysis, we found that lactate-derived carbon was incorporated into the TCA cycle and that lactate treatment was associated with restoration of Aβ-suppressed mitochondrial fluxes.

Humans↗

PubMed1988

Regional lactate production in early canine endotoxin shock.

High serum lactate may not reflect the severity of endotoxin shock: the lactate load could even be formed immediately after the endotoxin challenge. During the first 30 min after endotoxin injection (Escherichia coli; 1.5 mg/kg iv) into anesthetized dogs (4 mg.kg-1.h-1 etomidate, n = 19) we studied arterial lactate concentration; contributions of portal and splanchnic (n = 6), renal and pulmonary (n = 7), and femoral (n = 6) vascular beds to the early lactate rise; and regional O2 extraction and blood flow (microspheres). In control dogs (n = 5, no endotoxin), we found no significant hemodynamic and biochemical changes. Endotoxin caused an immediate decrease in blood pressure, cardiac output, and organ perfusion, followed by recovery after approximately 5 min to approximately 75% of preshock values at t = 30 min (except for renal blood flow, which remained low). Arterial lactate concentration started to increase almost immediately after endotoxin and increased rapidly until t = 15 min (to 300%) and then leveled off, but in spite of the hemodynamic recovery it remained elevated. A major part of the early increase in lactate concentration can be explained by splanchnic lactate production. The total splanchnic bed released more lactate than the portal bed, indicating that the liver produces lactate. We conclude that the lactate concentration later in canine endotoxin shock depends on events that occur during early shock in which the liver may play a crucial role.

Animals↗

PubMed1990

Subcutaneous adipose tissue: a source of lactate production after glucose ingestion in humans.

The in vivo kinetics of lactate and pyruvate in the extracellular space of subcutaneous adipose tissue after glucose ingestion were investigated in healthy volunteers by the use of a microdialysis sampling technique. Comparison was made with the metabolite levels in venous plasma. The absolute subcutaneous tissue concentrations of lactate and pyruvate were estimated in the fasting state by perfusion with varying lactate- and pyruvate-containing solutions. An equilibrium with the surrounding extracellular fluid was found for both lactate and pyruvate in concentrations similar to those in venous plasma. After glucose ingestion there was an increase in the circulating levels of glucose, lactate, and pyruvate, which returned to base-line values within 3 h. There was a more marked increase in lactate in subcutaneous adipose tissue than in venous blood, and the adipose tissue lactate remained elevated for at least 3 h. In contrast, pyruvate levels increased much less in subcutaneous fat than in venous blood. The addition of isoproterenol (which inhibits adipose tissue glucose metabolism) to the tissue perfusate lowered the subcutaneous tissue lactate levels significantly but did not affect the subcutaneous pyruvate levels. These data suggest that human subcutaneous adipose tissue is a source of in vivo lactate production after glucose ingestion. Since lactate is thought to be a major substrate for glycogen synthesis in the liver, the present findings may provide evidence of a new and important role of the adipose tissue metabolism in the regulation of whole body glucose homeostasis in humans.

Adipose Tissue↗

PubMed1994

Kinetics of the sarcolemmal lactate carrier in single heart cells using BCECF to measure pHi.

The pH-sensitive fluorescent indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) was used to measure lactate transport in single cardiac myocytes. Addition of lactate externally caused a rapid fall of intracellular pH (pHi), which was largely inhibited by 5 mM alpha-cyano-4-hydroxycinnamate (CHC), a specific inhibitor of the lactate carrier. Stilbene disulfonates such as 4,4'-dibenzamidostilbene-2,2'-disulfonate (DBDS) only partially inhibited the response, with inhibition being greater in guinea pig than rat myocytes. The data are consistent with two isoforms of the lactate carrier, one sensitive and one insensitive to DBDS, coexisting within a single myocyte and both having a stoichiometry of 1 lactate:1 proton. The initial rate of pHi fall was used to determine carrier kinetics. Rat myocytes had a Michaelis constant (Km) for external L-lactate of 2.74 mM and a Km for external pyruvate of 0.2 mM. Guinea pig cells had a Km for external L-lactate of 2.2 mM. Kinetics of lactate efflux were also evaluated using the rate of pHi recovery on removing external lactate. The Km and maximal rate values for efflux were both threefold higher than for influx and were related to each other and the transmembrane pH gradient as predicted by the Haldane relationship. It is suggested that under hypoxic conditions, the carrier may be the rate-limiting factor for lactate extrusion.

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

PubMed1980

Lactate absorption in Thamnophis proximal tubule: transport versus metabolism.

Proximal tubules from the kidney of Thamnophis (garter snake) were perfused in vitro and unidirectional fluxes of lactate measured using L(+)-[U-14C]lactate, (lactate concentration, 1 mM). The lumen-to-bath (absorptive) flux (Jlb lact) significantly exceeded the bath-to-lumen flux (backflux) (Jbl lact) in each of 12 tubules (seven distal proximal and five proximal proximal). The flux ratio (Jlb lact/Jbl lact) was approximately 3.00. At flow rates of 13-16 nl/min and lactate concentration of 1 mM the net flux was about 1.60 pmol . min-1 . mm-1 in both proximal proximal and distal proximal segments. Both fluxes were decreased by perfusion at 5 degrees C. To determin e the contribution of metabolism of lactate to its absorption, Jlb lact was measured at 25 degrees C in 10 distal proximal tubules during perfusion with [14C]lactate, lactate concentration, 1 mM, and with [methoxy-3H]inulin. In these experiments, the amount of 14C found in the bath was 93% of the amount of 14C absorbed from the lumen. Chromatography showed that all of the 14C found in the bath was [14C]lactate. These data establish that in Thamnophis proximal tubule lactate absorption occurs against an electro chemical gradient by transport of the intact lactate molecule without significant metabolism.

Absorption↗