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PubMed1976

Lactate metabolism in the dog during shock from hemorrhage, cardiac tamponade or endotoxin.

The elevated arterial lactate concentration in shock was investigated by measuring lactate production and clearance rate using a constant infusion of 14C-labeled lactate. In addition, the pathways of lactate metabolism were characterized by determining the percentage of lactate under-going oxidation and the percentage of the total carbon dioxide production which was derived from lactate. These measurements were performed on 16 normal dogs and on 23 dogs in a state of shock. Shock was induced by hemorrhage in ten, by controlled cardiac tamponade in seven and by endotoxin injection in six. In all of the dogs in a state of shock, there was a statistically significant increase in both the arterial lactate concentration and lactate turnover, while the lactate clearance decreased significantly. The percentage of the arterial lactate which underwent oxidation remained normal. The percentage of the total carbon dioxide production which was derived from lactate increased significantly, p less than 0.05, from 4.7 per cent in the normal dogs to 22.7 per cent in the dogs in a state of shock. Since both oxygen uptake and carbon dioxide production remain unchanged in shock, these data are consistent with an increased metabolism of substrates which from pyruvate and lactate as intermediary metabolites, that is, carbohydrates and certain amino acids, with a concomitant decrease in the metabolism of substrates which do not form pyruvate, that is, free fatty acids. In both the normal and shocked dogs, the arterial lactate concentration rose as the lactate production rate increased. Therefore, the elevated arterial lactate in shock was due to an increase in the lactate production and not to a lack of oxygen.

Animals↗
PubMed2001

Further studies on the effects of topical lactate on amino acid efflux from the ischemic rat cortex.

A rat four-vessel cerebral occlusion model was used to examine the effects of D-lactate and oxamate, a lactate dehydrogenase inhibitor, on cortical window superfusate levels of amino acids, glucose and L-lactate. Superfusate levels of aspartate, glutamate, taurine, GABA and phosphoethanolamine rose during ischemia and then declined during reperfusion. Glycine and alanine levels tended to increase during reperfusion, whereas glutamine levels were lower. Serine levels were not altered. Glucose levels declined rapidly during ischemia and recovered during reperfusion. Lactate levels were sustained during ischemia and increased during reperfusion. Unlike L-lactate, which attenuated ischemia/reperfusion (I/R) evoked amino acid release (J.W. Phillis, D. Song, L.L. Guyot, M.H. O'Regan, Lactate reduces amino acid release and fuels recovery of function in the ischemic brain, Neurosci. Lett. 272 (1999) 195-198), topical application of D-lactate (20 mM), which is not used as an energy substrate, enhanced the I/R release of aspartate, glutamate, GABA and taurine into cortical superfusates, and also elevated L-lactate levels above those in the controls. Glucose levels were not altered. Oxamate (20 mM) application elevated the pre-ischemia levels of alanine, glycine and GABA and those of GABA during ischemia. Levels of all amino acids, with the exception of phosphoethanolamine, were elevated during reperfusion. Oxamate, an inhibitor of lactate dehydrogenases 1 and 5, did not alter the pattern of efflux of glucose and L-lactate. In the presence of oxamate, L-lactate (20 mM) failed to inhibit amino acid release. The failure of D-lactate to attenuate amino acid release confirms the inability of this isomer to act as a metabolic substrate. The oxamate data indicate that inhibition of lactate dehydrogenase is detrimental to the viability of cortical cells during I/R, even though extracellular lactate levels are elevated. The pre-ischemia increases in alanine and glycine are suggestive of elevations in pyruvate as a result of the block of its conversion to lactate, with transamination reactions converting pyruvate to form these amino acids. In summary, the results further substantiate the concept of a role for L-lactate as a cerebral energy substrate.

Administration, Topical↗
PubMed2001

Evaluation of the Accusport lactate analyser.

It has been suggested that lactate concentrations may provide a guide to an optimal training intensity. However, lactate concentrations established during incremental exercise in the laboratory are not always indicative of what is occurring during constant-load exercise at the same intensity. Ideally, lactate concentrations should be measured during a training session and immediately reported to the athlete to ensure that the athlete is working at the desired intensity. The purpose of this investigation was, therefore, to determine the reliability and validity of a compact, portable lactate analyser (ACCUSPORT; Boeringer Mannheim, Castle Hill, Australia). A total of 224 capillary blood samples were taken from athletes who took part in routine laboratory testing. Seventy-three of these capillary blood samples were analysed in duplicate with the Accusport for determination of intraclass, single-trial reliability. Day-to-day intraclass reliability of the Accusport was assessed by analyzing known concentrations of aqueous lactate solutions on seven consecutive days. The validity of the Accusport analyser was assessed by comparing the 224 capillary blood lactate concentrations determined on the Accusport with the lactate concentration obtained using a MICRO STAT LM3 (Analox Instruments Ltd., London, UK). In addition, lactate parameters derived from the lactate concentrations obtained with the two analysers were compared. The Accusport showed high single-trial intraclass reliability (R = 0.992; Standard Error of Measurement [SE(M)] = 0.3 mmol x l(-1); n = 73) and high day-to-day intraclass reliability (R = 0.993; SE(M) = 0.4 mmol x l(-1); n = 42). Despite a strong correlation between blood lactate concentrations obtained on the two analysers (r = 0.96; n = 224) the limits of agreement were + 1.9 to - 2.2 mmol x l(-1). Although the mean values for power output, HR and lactate concentration associated with the lactate parameters were not significantly different when determined on the Accusport or Micro Stat, some individuals did record large differences between analysis methods. In summary, the results of this investigation have shown that lactate concentrations can be reliably determined within a single trial and from day-to-day using the Accusport analyser. However, for some athletes, it is not valid to compare lactate concentrations or lactate parameters determined on the Accusport with those determined using the Micro Stat LM3 lactate analyser.

Adult↗
PubMed1998

The relationship between plasma lactate parameters, Wpeak and 1-h cycling performance in women.

PURPOSE: The relationship between six descriptors of lactate increase, peak VO2, Wpeak, and 1-h cycling performance were compared in 24 trained, female cyclists (peak VO(2) = 48.11 +/- 6.32 mLxkg(-1)xmin(-1). METHODS: The six descriptors of lactate increase were: 1) lactate threshold (LT; the power output at which plasma lactate concentration begins to increase above the resting level during an incremental exercise test), 2) LT(1) the power output at which plasma lactate increases by 1 mM or more), 3) LT(D) (the lactate threshold calculated by the D-max method), 4) LT(MOD) (the lactate threshold calculated by a modified D-max method), 5) L4 (the power output at which plasma lactate reaches a concentration of 4 mmolxL(-1), and 6) LT(LOG) (the power output at which plasma lactate concentration begins to increase when the log ([La(-1]) is plotted against the log (power output). Subjects first completed a peak VO(2) test on a cycle ergometer. Finger-tip capillary blood was sampled within 30 s of the end of each 3-min stage for analysis of plasma lactate. Endurance performance was assessed 7 d later using a 1-h cycle test (OHT) in which subjects were directed to achieve the highest possible average power output. RESULTS: The mean power output (W) for the OHT (+/- SD) was 183.01 +/- 18.88, and for each lactate variable was:LT (138.54 +/- 46.61), LT(1) (179.17 +/- 27.25), LT(log) (143.97 +/- 45.74), L4 (198.09 +/- 33.84), LT(D) (178.79 +/- 24.07), LT(MOD)(212.28 +/- 31.75). Average power output during the OHT was more strongly correlated with all plasma lactate parameters (0.61<r<0.84) and W(peak) (r = 0.81) than with peak VO(2) (r = 0.55). The six lactate parameters were strongly correlated with each other (0.54<r<0.91) and of six lactate parameters, LT(D) correlated best with endurance performance (r = 0.84). CONCLUSIONS: It was concluded that plasma lactate parameters and W(peak) provide better indices of endurance performance than peak VO(2) and that, of the six descriptors of lactate increase measured in this study, LT(D) is most strongly related to 1-h cycling performance in trained, female cyclists.

Adult↗
PubMed1999

A new method for rapid measurement of lactate in fetal and neonatal blood.

A prospective trial to determine the accuracy and precision of the Boehringer Mannheim Accusport handheld lactate meter in measuring plasma lactate levels in umbilical cord blood and neonatal blood microsamples was performed in the labour ward and the neonatal intensive care unit of the NepeanHospital. Specimens were collected from the umbilical artery of 160 consecutive deliveries covering gestations from 26 to 42 weeks, and from 110 umbilical artery catheters covering a range of gestations from 26 to 41 weeks. Serum was also obtained from an exchange transfusion for coefficient of variation analysis. Blood was simultaneously tested for lactic acid concentration on the Boehringer Mannheim (BM) Accusport held lactate meter and the Radiometer ABL 625 blood-gas machine. Clinical data from the mother and baby were recorded together with the full blood-gas analysis for comparison with the lactate measures. Coefficients of variation for the BM Accusport lactate meter were established by a further 120 samples of plasma lactate at 6 concentrations from 1 to 20 mmol/L. The stability of measurements with the BM lactate meter over a wide range of temperatures was ascertained by repeated sampling of known concentrations of plasma lactate from 0.5 degrees C to 37 degrees C. The BM Accusport lactate meter was found to be accurate from 1 mmol/L to 20 mmol/L with a Passing Bablok regression line y = 0.004 + 0.915 x (95% CI of slope of 0.889 to 0.946 and intercept -0.138 to 0.094) for whole blood, and y = 0.200 + 1.000 x (95% CI of slope 0.989 to 1.018 and intercept 0.080 to 0.222) for plasma. Between run coefficient of variation (CV) was calculated to be 1.23% to 5.53% over the clinically significant range (2.2-19.3 mmol/L). The BM lactate meter was accurate from 5 to 37 degrees C. At 0.5 degrees C the BM lactate meter significantly underestimated the plasma lactate concentration. There was no significant effect of haematocrit (41.5 to 62%), gestation, or operator on the accuracy of the BM lactate meter. The Accusport handheld lactate meter is an accurate, commercially available, method of measuring plasma lactate levels in only 60 seconds at the point-of-care. It requires only 15 microL of blood and is significantly cheaper than other assay methods. The BM lactate meter is well suited to assess lactic acidaemia of fetal scalp and neonatal blood samples to help quantify hypoxic stress in the perinatal period.

Blood Chemical Analysis↗
PubMed1998

Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction.

A prospective study was conducted on 34 stable septic patients to determine whether mild hyperlactatemia is a marker of lactate overproduction or an indicator of lactate underutilization during sepsis. Plasma lactate clearance and lactate production were evaluated by modeling the lactate kinetic induced by an infusion of 1 mmol/kg L-lactate over 15 min. The patients were divided in two groups depending on their blood lactate: < or = 1.5 mmol/L (n = 20, lactate = 1.2+/-0.2 mmol/L) or > or = 2 mmol/L (n = 10, lactate = 2.6+/-0.6 mmol/L). The hyperlactatemic patients had a lower lactate clearance (473+/-102 ml/kg/h) than those with normal blood lactate (1,002+/-284 ml/kg/h, p < 0.001), whereas lactate production in the two groups was similar (1,194+/-230 and 1,181+/-325 micromol/kg/h, p = 0.90). A second analysis including all the patients confirmed that the blood lactate concentration was closely linked to the reciprocal of lactate clearance (r2 = 0.73, p < 0.001) but not to lactate production (r2 = 0.03, p = 0.29). We conclude that a mild hyperlactatemia occurring in a stable septic patient is mainly due to a defect in lactate utilization.

Adult↗
PubMed2005

Lactate--a signal coordinating cell and systemic function.

Since its first documented observation in exhausted animal muscle in the early 19th century, the role of lactate (lactic acid) has fascinated muscle physiologists and biochemists. Initial interpretation was that lactate appeared as a waste product and was responsible in some way for exhaustion during exercise. Recent evidence, and new lines of investigation, now place lactate as an active metabolite, capable of moving between cells, tissues and organs, where it may be oxidised as a fuel or reconverted to form pyruvate or glucose. The questions now to be asked concern the effects of lactate at the systemic and cellular level on metabolic processes. Does lactate act as a metabolic signal to specific tissues, becoming a metabolite pseudo-hormone? Does lactate have a role in whole-body coordination of sympathetic/parasympathetic nerve system control? And, finally, does lactate play a role in maintaining muscle excitability during intense muscle contraction? The concept of lactate acting as a signalling compound is a relatively new hypothesis stemming from a combination of comparative, cell and whole-organism investigations. It has been clearly demonstrated that lactate is capable of entering cells via the monocarboxylate transporter (MCT) protein shuttle system and that conversion of lactate to and from pyruvate is governed by specific lactate dehydrogenase isoforms, thereby forming a highly adaptable metabolic intermediate system. This review is structured in three sections, the first covering pertinent topics in lactate's history that led to the model of lactate as a waste product. The second section will discuss the potential of lactate as a signalling compound, and the third section will identify ways in which such a hypothesis might be investigated. In examining the history of lactate research, it appears that periods have occurred when advances in scientific techniques allowed investigation of this metabolite to expand. Similar to developments made first in the 1920s and then in the 1980s, contemporary advances in stable isotope, gene microarray and RNA interference technologies may allow the next stage of understanding of the role of this compound, so that, finally, the fundamental questions of lactate's role in whole-body and localised muscle function may be answered.

Exercise↗
PubMed1983

Whole-body metabolism of glucose and lactate in productive sheep and cows.

Constant infusions of D-[U-14C]glucose, D-[6-3H]glucose and L-[U-14C]lactate were used to determine rates of apparent turnover, de novo production, disposal and interconversions of glucose and lactate, together with total recycling of glucose-C, in ewes and dairy cows during late pregnancy and early lactation. The cows were also examined while being fasted. In the fed animals, infusions were made within 5 h after the morning meal when steady-state conditions appeared to exist. In the ewes, circulating concentrations of glucose and lactate, and magnitudes of apparent turnovers of glucose and lactate, tended to be higher during lactation than during pregnancy, while the extent of interconversions of glucose and lactate tended to be lower. Although the metabolic pattern seen in the cows appeared to be similar to that of the ewes during pregnancy, there were clear differences during lactation. Thus, in the lactating cows, as compared with the lactating ewes, circulating concentrations of glucose and lactate were lower, as was apparent turnover related to metabolic body-weight. Furthermore, the percentage of lactate turnover converted to glucose was higher. In the cows, fasting was characterized by low rates of apparent turnover of glucose and lactate and relatively high rates of interconversion of the two compounds. The results indicated that, under the conditions used in this study and when feeding is to recommended levels, carbohydrate metabolism in ewes is more precarious during late pregnancy than during early lactation, while in dairy cows it is more or less equally precarious in both physiological states. A further conclusion is that the extent of glucose-lactate interconversions, and thus Cori cycle activity, seems to be lower in ruminants than in other species.

Animals↗
PubMed1983

Effects of physiologic concentrations of lactate, pyruvate and ascorbate on glucose metabolism in unstressed and oxidatively stressed human red blood cells.

Glucose metabolism was studied in human red blood cells incubated in the presence of physiologic concentrations of ascorbate (0.1 mM) and/or lactate (2 mM) plus pyruvate (0.1 mM). The total flux through glycolysis, as measured by 14C-labeling of glycolytic intermediates, was increased about 15% by ascorbate, 30% by lactate plus pyruvate, and 40% by ascorbate plus lactate plus pyruvate. We found, however, that physiologic concentrations of ascorbate and/or lactate plus pyruvate had no effect on flux of glucose or recycling of pentoses through the hexose monophosphate shunt. Increased formation of lactate accounted for most of the observed increase in glycolysis with little change in pyruvate formation, indicating that the increased flux of reducing equivalents from glucose was stored as lactate rather than being consumed by red cell metabolism. In all experiments, there was a net increase with time in the absolute amount of both lactate and pyruvate in red cell suspensions, indicating that lactate or pyruvate present at zero time did not function as a stoichiometric source or sink for reducing equivalents. There was little effect on steady-state levels of ATP or 2,3-diphosphoglycerate. Equilibration of ascorbate between red cells and the medium was complete before the addition of 14C-labeled glucose to the medium. Glucose metabolism prevented net oxidation of ascorbate in the incubation medium. Physiologic concentrations of ascorbate, lactate and pyruvate appear to increase flux through glycolysis by increasing the turnover of ATP and/or 2,3-diphosphoglycerate. Red cells were exposed to mild oxidative stress by incubation with 0.27 mM 6-hydroxydopamine, 0.27 mM 6-aminodopamine, 0.13 mM 1,4-naphthoquinone-2-sulfonic acid or 0.27 mM phenylhydrazine. The metabolic response to oxidative stress was determined by measuring the formation of methemoglobin, pyruvate, lactate and CO2 in the presence and absence of physiologic concentrations of lactate, pyruvate and ascorbate. Lactate, pyruvate and ascorbate had no effect on the net methemoglobin accumulation but rather on the distribution of the metabolic sources of reducing equivalents and on the flux of reducing equivalents to oxygen. Physiologic lactate and pyruvate allowed increased flow of reducing equivalents from glycolysis to methemoglobin and ultimately oxygen without the necessity of increased flux through glycolysis. This was accomplished by a decrease in the ratio of newly formed lactate to newly formed pyruvate with no increase in total lactate plus pyruvate.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Effects of D-3-hydroxybutyrate and acetoacetate on lactate removal in isolated perfused livers from starved and fed rats.

We examined the influence of nutritional state on the role of the hepatic plasma membrane lactate transporter in determining overall hepatic lactate disposal. The effects of infusion of sodium D-3-hydroxybutyrate (DOHB) on lactate uptake were studied in perfused livers from fed or starved rats. In livers from starved rats, DOHB (15 to 20 mmol/L) inhibited lactate removal by approximately 45%. This effect was associated with a decrease in intracellular lactate concentration, with cell pH remaining unchanged. Inhibition was maximal when perfusate lactate was less than 1.6 mmol/L, and was undetectable at concentrations exceeding 2.5 mmol/L. A similar degree of inhibition was observed with infusion of acetoacetate. These observations add to the evidence that the inhibition of lactate removal by DOHB seen in livers from starved animals is mediated through an effect on the hepatocyte lactate transporter. At similar low levels of perfusate lactate, DOHB infusion produced a decrease in output of lactate from livers obtained from fed animals. When such livers were subjected to prolonged preperfusion, lactate removal, rather than output, was observed; in these livers DOHB stimulated lactate removal, an effect directionally opposite to that observed in livers from starved animals. These data confirm that hepatic lactate transport is a limiting factor for lactate utilization in intact livers from starved rats; in contrast, lactate utilization in livers from fed animals is limited at a step subsequent to plasma membrane transport, ie, possibly pyruvate transport into mitochondria.

3-Hydroxybutyric Acid↗
PubMed1981

Cellular uptake of L-lactate in mouse diaphragm.

Early uptake curves of L-lactate and of mannitol were measured in quartered, incubated mouse diaphragms. Uptake was determined at 15, 30, and 45 s for various concentrations of lactate in the external solution as well as in the presence and absence of the competitive inhibitor of lactate transport, alpha-cyano-4-hydroxycinnimate. In normal preparations, when the external lactate concentration was 10 mM or less, the ratio of lactate-to mannitol space in the tissue was 1.7. This value was nearly independent of time and of external concentration. In normal preparations, when the external lactate concentration was greater than 10 mM, the ratio of lactate-to-mannitol space rose with time. At a fixed time, however, this ratio fell with increasing lactate concentration. In the inhibited preparations, the ratio of lactate-to-mannitol space rose with time at all concentrations. When lactate concentration was greater than 5 mM, this ratio was independent of the external concentration. The results suggest that there are two modes of lactate entry into these muscle cells. Entry can occur by means of a saturable system. When external lactate concentration is low, entry rates for this process are rapid compared with diffusional rates. This system probably saturates at concentrations near 10 mM and can facilitate transport in either direction. In addition, an appreciable passive leak is present. This leak accounts for about one fourth of the membrane transfer when external lactate is low, but is equal to the carrier transfer when lactate concentration is 30 mM. A model was developed to describe the entry of a permeating solute, such as lactate, into an isolated tissue.

Animals↗
PubMed1990

Insulin resistance of glucose metabolism in isolated brown adipocytes of lactating rats. Evidence for a post-receptor defect in insulin action.

The mechanism responsible for the insulin resistance described in vivo in brown adipose tissue (BAT) of lactating rats was investigated. The effect of insulin on glucose metabolism was studied on isolated brown adipocytes of non-lactating and lactating rats. Insulin stimulation of total glucose metabolism is 50% less in brown adipocytes from lactating than from non-lactating rats. This reflects a decreased effect of insulin on glucose oxidation and lipogenesis. However, the effect of noradrenaline (8 microM) on glucose metabolism was preserved in brown adipocytes from lactating rats as compared with non-lactating rats. The number of insulin receptors is similar in BAT of lactating and non-lactating rats. The insulin-receptor tyrosine kinase activity is not altered during lactation, for receptor autophosphorylation as well as tyrosine kinase activity towards the synthetic peptide poly(Glu4-Tyr1). The defect in the action of insulin is thus localized at a post-receptor level. The insulin stimulation of pyruvate dehydrogenase activity during euglycaemic/hyperinsulinaemic clamps is 2-fold lower in BAT from lactating than from non-lactating rats. However, the percentage of active form of pyruvate dehydrogenase is similar in non-lactating and lactating rats (8.6% versus 8.9% in the basal state, and 37.0% versus 32.3% during the clamp). A decrease in the amount of pyruvate dehydrogenase is likely to be involved in the insulin resistance described in BAT during lactation.

Adipose Tissue, Brown↗
PubMed1998

Reduced noradrenergic tone to the hypothalamic paraventricular nucleus contributes to the stress hyporesponsiveness of lactation.

Lactation in mammals is accompanied by a marked decrease in stress responsiveness that we previously attributed, in part, to a reduction in noradrenergic (NA) innervation of hypothalamic paraventricular nucleus (PVN) neurons controlling neuroendocrine stress responses. In the present study, we compared in-vivo PVN catecholamine secretion by microdialysis between nonlactating and lactating females and tested the effects of NA alpha-1 and alpha-2 receptor antagonists (corynanthine and idazoxan, respectively) on the acute stress response of lactating and virgin female rats. To determine if PVN alpha-adrenoreceptor density, affinity, or synthesis, changes as a function of lactation, we performed receptor autoradiography, Scatchard analysis and in situ hybridization of alpha-adrenoreceptors. Densitometric analysis of the alpha-adrenoreceptors in the supraoptic nucleus (SON) was used to evaluate changes in magnocellular neurons. Endogenous PVN norepinephrine release under basal conditions was lower in lactating females than in females who had their pups removed for 2 days, and microdialysate concentrations of adrenaline and MHPG were attenuated in lactating females. Alpha-2 adrenoreceptor density in the PVN showed a significant decrease from lactation day 3 to lactation days 10-12 and a reduction to 40% of virgin controls on days 10-20 of lactation. A similar pattern was observed for the SON. The affinity of hypothalamic alpha-2 adrenoreceptors was reduced as a function of lactation. Alpha-1 adrenoreceptor density in the PVN and in the hypothalamus rose as a function of lactation, although the affinity of these receptors was not altered. In contrast, alpha-1D adrenoreceptor subtype mRNA expression in the PVN decreased in middle lactating females (day 10) compared to virgins. Intracerebroventricular (i.c.v.) application of idazoxan, significantly increased the ACTH response to swim stress in virgin females, but had the opposite effect in lactating females. In contrast, i.c.v. corynanthine treatment significantly decreased the ACTH response in virgins, but not in lactating females. Overall, these data suggest that the secretion of NA in the PVN is reduced during lactation, and that the ability of PVN parvocellular neurons to respond to changes in synaptic NA levels (i.e. after stress) is also altered.

Adrenergic alpha-Antagonists↗
PubMed2001

Cerebrospinal-fluid lactate in adult mitochondriopathy with and without encephalopathy.

Despite improved diagnostic facilities, the diagnosis of mitochondriopathy (MCP) is sometimes difficult to establish. This study aimed to investigate whether CSF lactate can be of diagnostic help in this respect. Cerebrospinal-fluid (CSF) lactate and its relation to resting lactate and lactate stress testing were investigated in 26 MCP patients, aged 30-84 years. The upper reference limit of CSF lactate, obtained from 28 healthy subjects, was 1.6 mmol/l. Seven MCP patients (27%) had elevated CSF lactate. Five of these patients had central nervous system (CNS) abnormalities other than elevated CSF lactate. In two patients with increased cerebrospinal-fluid lactate, lactate stress testing was normal or could not be carried out. In conclusion, CSF lactate is elevated in one quarter of adult MCP patients. CSF lactate is preferentially elevated in patients with additional CNS abnormalities other than elevated CSF lactate. If the results for resting lactate or lactate stress testing are normal or unavailable, determination of CSF lactate may be of diagnostic support in single cases.

Adult↗
PubMed2005

Lactation decreases pancreatic lipase mRNA level in the rat.

Lactation alters maternal metabolism and increases food intake in rats to support milk production. Pancreatic lipase (PL) is primarily responsible for fat digestion in adults and is regulated by dietary fat. The present research determined the regulation of PL by lactation and dietary fat. In Expt 1, eighteen Sprague-Dawley dams and twelve age-matched virgins (controls) were fed a low-fat diet (LF; 11 % energy as safflower oil) for 7-63 d. At postpartum (day 0), peak lactation (day 15) and post-lactation (day 56) and after 7 d in virgins, the pancreas was removed for mRNA and enzyme analyses. In Expt 2, thirty-six Sprague-Dawley dams were fed LF until day 9 postpartum when dams were divided into three groups of twelve; one continued to be fed LF, one was fed a moderate-fat diet (MF; 40 % energy as safflower oil); and one was fed a high-fat diet (HF; 67 % energy as safflower oil) diet. At peak lactation (day 15) and post-lactation (day 56), the pancreas was removed for mRNA and enzyme analyses. Expt 1 revealed that lactation and post-lactation significantly (P<0.001) decreased PL mRNA (67 % and 76 %, respectively), but only post-lactation decreased PL activity. Increased dietary fat in Expt 2 significantly increased PL mRNA (LF<MF<HF, P<0.001) and PL activity (LF<MF=HF, P<0.02) in both lactation and post-lactation. In summary, lactation and post-lactation decreased PL mRNA significantly even though dietary fat still regulated PL activity and mRNA in lactation and post-lactation.

Animals↗
PubMed1980

Preferential uptake of lactate by the normal myocardium in dogs.

This study was undertaken to investigate whether the normal dog heart would switch to lactate as the preferred substrate when the arterial lactate level was raised. Sodium L-Lactate (pH adjusted to 7.0) was infused intravenously in sufficient quantity to raise the arterial lactate levels to those found in moderate to severe exercise (over 4.5 mmol . litre-1). The dogs were studied under chloralose anaesthesia breathing spontaneously. Blood samples were obtained from a branch of the femoral artery and the coronary sinus, and analysed for lactate, glucose, fatty free acids (FFA) and oxygen content. The ratio of lactate consumption to oxygen consumption was used to express the amount of lactate oxidised as a percentage of total substrate. This ratio was found to be a function of arterial lactate and reached a maximum at an arterial lactate concentration of 4.5 mmol . litre-1; this was uninfluenced by raised arterial glucose or FFA--the myocardium preferred lactate to glucose or FFA. A direct measurement of lactate oxidised as a percentage of total fuel was obtained in experiments with L-Lactate-[14C(U)], these showed that when the arterial lactate concentration was above 4.5 mmol . litre-1, even in the presence of high glucose or FFA, 87% of the total substrate oxidised was lactate. These results show that when the normal dog heart is presented with a choice of substrates, lactate is the preferred substrate for energy production.

Animals↗
PubMed1997

Use of different anticoagulants in test tubes for analysis of blood lactate concentrations: Part 2. Implications for the proper handling of blood specimens obtained from critically ill patients.

OBJECTIVES: a) To test the hypothesis that the measurement of the circulating lactate concentration is influenced by the anticoagulant in the test tube that contains the blood sample; b) to test the hypothesis that the measurement of the circulating lactate concentration is influenced by the tissue used for analysis. DESIGN: A prospective, controlled study. SETTING: A critical care research laboratory, a 20-bed intensive care unit (ICU), and the general wards. SUBJECTS: Twenty-three ICU and ward patients with hyperlactatemia and 19 healthy volunteers. INTERVENTIONS: Blood samples were collected for determination of blood lactate concentration. MEASUREMENTS AND MAIN RESULTS: Venous blood samples (12 mL) were obtained from each of the 19 normal subjects and each 12-mL specimen was evenly divided into six aliquot portions (six test tubes). Experiment 1: Of the six tubes, two tubes were set aside for experiment 2. The other four tubes were used to test four anticoagulants (one anticoagulant per tube). The anticoagulants tested were: sodium heparin; EDTA; lithium heparin; and sodium citrate. Lactate concentrations were analyzed using an ion-selective, amperometric electrode that we have previously validated. There were no statistically significant differences between the lactate concentrations derived from blood samples stored in sodium heparin, EDTA, or lithium heparin (p > .05; n = 19; Student-Newman-Keuls' multiple comparisons test). The lactate concentration of blood stored in sodium citrate, however, was lower than all other anticoagulants (p < .001; n = 19; Student-Newman-Keuls' multiple comparisons). Experiment 2: Of the remaining two test tube samples from each subject, one tube contained sodium heparin and the other tube did not contain an anticoagulant. Each of these two tubes was centrifuged at 50 degrees F (10 degrees C) for 15 mins to obtain plasma and serum samples. Lactate concentrations were measured in the serum and plasma and compared with those concentrations found in whole blood samples from the tube containing sodium heparin from experiment 1. The plasma and serum lactate concentrations were consistently higher than the whole blood lactate values from the same specimen (p < .05; n = 42; Student-Newman-Keuls' multiple comparisons test). Since experiment 1 involved the collection of blood from healthy volunteers with normal lactate concentrations, we chose to investigate whether this discordance between plasma or serum and whole blood was dependent on the lactate concentration. To answer this question, we studied 23 patients with known hyperlactatemia and found that in subjects with a lactate concentration of < 2.2 mmol/L, there was a difference of 0.11 mmol/L in the mean values between plasma and whole blood concentrations (p < .0004; n = 19; paired t-test). In subjects with a lactate concentration of > 2.2 mmol/L, there was a difference of 0.14 mmol/L (p < .0001; n = 23; paired t-test) in the mean values between plasma and whole blood. In all samples at all concentrations, there was no significant difference between serum vs. plasma samples (p > .05; Student-Newman-Keuls' test). CONCLUSIONS: a) Sodium citrate, as an anticoagulant, caused lower lactate concentrations to be measured as compared with heparin or EDTA; b) the measurement of lactate concentrations in plasma or serum samples yields a higher value than the concentration found in the original whole blood specimen.

Anticoagulants↗
PubMed2001

Evidence of separate pathways for lactate uptake and release by the perfused rat heart.

The simultaneous release and uptake of lactate by the heart has been observed both in vivo and ex vivo; however, the pathways underlying these observations have not been satisfactorily explained. Consequently, the purpose of this study was to test the hypothesis that hearts release lactate from glycolysis while simultaneously taking up exogenous lactate. Therefore, we determined the effects of fatty acids and diabetes on the regulation of lactate uptake and release. Hearts from control and 1-wk diabetic animals were perfused with 5 mM glucose, 0.5 mM [3-(13)C]lactate, and 0, 0.1, 0.32, or 1.0 mM palmitate. Parameters measured include perfusate lactate concentrations, fractional enrichment, and coronary flow rates, which enabled the simultaneous, but independent, measurements of the rates of 1) uptake of exogenous [(13)C]lactate and 2) efflux of unlabeled lactate from metabolism of glucose. Although the rates of lactate uptake and efflux were both similarly inhibited by the addition of palmitate, (i.e., the ratio of lactate uptake to efflux remained constant), the ratio of lactate uptake to efflux was significantly higher in the controls compared with the diabetic group (1.00 +/- 0.14 vs. 0.50 +/- 0.07, P < 0.002). These data, combined with heterogeneous (13)C enrichment of tissue lactate, pyruvate, and alanine, suggest that glycolytically derived lactate production and oxidation of exogenous lactate operate as functionally separate metabolic pathways. These results are consistent with the concept of an intracellular lactate shuttle.

Alanine↗