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Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study.

BACKGROUND: Hyperlactataemia during septic shock is often viewed as evidence of tissue hypoxia. However, this blood disorder is not usually correlated with indicators of perfusion or diminished with increased oxygen delivery. Muscles can generate lactate under aerobic conditions in a process linking glycolytic ATP supply to stimulation of Na+K+ ATPase. Using in-vivo microdialysis, we tested whether inhibition of Na+K+ ATPase can reduce muscle lactate. METHODS: In 14 patients with septic shock, two microdialysis probes were inserted into the quadriceps muscles and infused with lactate-free Ringer's solution in the absence or presence of 10(-7) mol/L ouabain, a specific inhibitor of Na+K+ ATPase. We measured lactate and pyruvate concentrations in both the dialysate fluid and arterial blood samples. FINDINGS: All patients had increased blood lactate concentrations (mean 4.0 mmol/L; SD 2.1). Lactate and pyruvate concentrations were consistently higher in muscle than in arteries during the study period, with a mean positive gradient of 1.98 mmol/L (SD 0.2; p=0.001) and 230 micromol/L (30; p=0.01), respectively. Ouabain infusion stopped over production of muscle lactate and pyruvate (p=0.0001). Muscle lactate to pyruvate ratios remained unchanged during ouabain infusion with no differences between blood and muscle. INTERPRETATION: Skeletal muscle could be a leading source of lactate formation as a result of exaggerated aerobic glycolysis through Na+K+ ATPase stimulation during septic shock. Lactate clearance as an end-point of resuscitation could therefore prove useful. RELEVANCE TO CLINICAL PRACTICE: In patients with septic shock, a high lactate concentration should be interpreted as a marker of disease, portending a bad outcome. The presence of hyperlactataemia in resuscitated septic patients should not be taken as proof of oxygen debt needing increases in systemic or regional oxygen transport to supranormal values. Lactate, instead of being regarded only as a marker of hypoxia, might be an important metabolic signal.

Aerobiosis↗
PubMed2001

Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer.

PURPOSE: Hypoxia shifts the balance of cellular energy production toward glycolysis with lactate generation as a by-product. Quantitative bioluminescence imaging allows for the quantitation of lactate concentrations in individual tumors. We assessed the relationship between pretreatment tumor lactate concentrations and subsequent development of metastatic disease in patients with newly diagnosed head-and-neck cancer. METHODS AND MATERIALS: At the time of biopsy of the primary site, a separate specimen was taken and flash-frozen for subsequent quantitation of lactate concentration using a luciferase bioluminescence technique. The two-dimensional spatial distribution of the bioluminescence intensity within the tissue section was registered directly using a microscope and an imaging photon counting system. Photon intensity was converted to distributions of volume-related tissue concentrations (micromol per gram wet weight). Treatment consisted of either surgery and postoperative radiotherapy or primary radiotherapy, based on presenting disease stage and institutional treatment policies. The subsequent development of metastatic disease constituted the primary clinical endpoint. RESULTS: Biopsies obtained from 40 patients were evaluable in 34. The larynx was the most frequent primary site (n = 25). Other sites included oropharynx (n = 5), hypopharynx (n = 3), and oral cavity (n = 1). Most patients (74%) presented with an advanced stage T3 or T4 primary tumor. Nodal involvement was present in 19 (54%) patients. The median tumor lactate concentration was 7.1 micromol/g. Tumors were classified as having either low or high lactate concentrations according to whether these values were below or above the median. The median follow-up time for surviving patients is 27 months. Two-year actuarial survival was 90% for patients with low-lactate-concentration tumor vs. 35% for patients with high-lactate-concentration primaries (<0.0001). Two-year metastasis-free survival was adversely influenced by high tumor lactate concentrations (90% vs. 25%, p < 0.0001). The median lactate concentration for tumors that subsequently metastasized was 12.9 micromol/g vs. 4.8 micromol/g for patients who remained continuously free of disease (p < 0.005). Lactate concentration was not correlated with presenting T stage or N stage. DISCUSSION: Elevated tumor lactate concentrations are associated with the subsequent development of nodal or distant metastases in head-and-neck cancer patients. This more aggressive malignant phenotype is probably associated with hypoxia-mediated radioresistance and the upregulation of metastasis-associated genes.

Biomarkers, Tumor↗
PubMed1999

Lactate attenuates neuron specific enolase elevation in newborn rats.

This study was undertaken to investigate the protective role of lactate on the hypoxic brain in newborn rats. A total of 107 7-day-old Wistar rats were divided into three groups. The lactate accumulation group was given 5% oxygen and 95% nitrogen for 30 minutes. The lactate elimination group was given 5% oxygen, a concentration of 7.5% carbon dioxide, and 87.5% nitrogen for 30 minutes. The control rats were placed in room air. Lactate levels in the brain tissue were higher in the lactate accumulation group than in those of the control group (control: 1.78 +/- 0.91, lactate accumulation: 11.42 +/- 1.64 mmol/kg) and significantly decreased in the lactate elimination group (4.10 +/- 1.73 mmol/kg). Blood pH remained at the same levels in the two groups. Neuron specific enolase in the cerebrospinal fluid, which is the initial neurocyte damage marker, was significantly elevated in the lactate elimination group (control: 18.3 +/- 7.5, lactate accumulation: 18.8 +/- 7.9, lactate elimination: 63.1 +/- 61.3 ng/mL). Brain adenosine 5'-triphosphate levels were significantly decreased in the lactate elimination group. Histologic findings of the brain at 72 hours after the load revealed no abnormal changes in any of the groups examined. The authors conclude that lactate accumulation plays a protective role on the hypoxic brain in newborn rats.

Adenosine Triphosphate↗
PubMed1997

Single-voxel 1H-MRS investigation of brain metabolic changes during lactate-induced panic.

Intravenous sodium lactate infusion is a robust laboratory technique for eliciting panic in susceptible individuals. The objective for this study was to replicate previous work which found differential brain lactate rises among lactate-sensitive panic subjects relative to control subjects using single-voxel 1H-magnetic resonance spectroscopy (MRS). Single-voxel 1H-MRS was used to measure brain lactate changes in the insular cortex region among 13 panic disorder subjects and 10 healthy control subjects during the infusion. One panic subject prematurely terminated the study due to a panic response during lactate infusion. Data from two additional control subjects and one panic subject were lost due to technical problems. Four panic subjects were reinfused with lactate while panic-free under treatment with fluoxetine (20 mg/day). At the time of initial infusion, all subjects were medication-free for at least 1 month. Ten panic subjects, but no control subjects, panicked during lactate infusion. In comparison to control subjects, panic subjects demonstrated significantly greater and prolonged brain lactate rises in the insular cortex region. Three of four medicated panic subjects experienced blockage of panic symptoms during lactate reinfusion but all exhibited persistent excesses in brain lactate rise. Consistent with our prior observations, greater and prolonged lactate rises in the insular brain region occur during and following lactate infusion among panic subjects compared to control subjects. This differential brain metabolic response did not appear to normalize when a small subset of panic patients were reinfused following resolution of panic symptoms during treatment over 3-4 months with fluoxetine.

Adult↗
PubMed2000

Modeling brain compartmental lactate response to metabolic challenge: a feasibility study.

Magnetic resonance spectroscopy has been used to characterize abnormal brain lactate response in panic disorder (PD) subjects following lactate infusion. The present study integrated water quantification and tissue segmentation to evaluate compartmental lactate response within brain and cerebrospinal fluid (CSF). As there is evidence of brain parenchymal pH changes during lactate infusion, water scans were collected at baseline and post-infusion to address brain water stability. Water levels remained essentially stable across the protocol suggesting internal water provides an improved reference signal for measuring dynamic changes in response to metabolic challenge paradigms such as lactate infusion. To model brain lactate changes by compartments, we took the null hypothesis that lactate rises occur only in tissue. The approach referenced lactate amplitude (potentially from both compartments) to 'voxel' water (water scan corrected for differential T(2) between CSF brain at long-echo times - synonymous to a short-echo water scan). If the magnitude of lactate rise in CSF was equal to or greater than brain, voxels with substantial CSF fractions should demonstrate an equivalent or elevated response to voxels comprised only of tissue. The magnitude of lactate increases paralleled voxel tissue fraction suggesting the abnormal lactate rise observed in PD is tissue-based. The feasibility of lactate quantification and compartmental modeling are discussed.

Adult↗
PubMed2000

The 'lactate paradox', evidence for a transient change in the course of acclimatization to severe hypoxia in lowlanders.

The metabolic response to exercise at high altitude is different from that at sea level, depending on the altitude, the rate of ascent and duration of acclimatization. One apparent metabolic difference that was described in the 1930s is the phenomenon referred to as the 'lactate paradox'. Acute exposure to hypoxia results in higher blood lactate accumulation at submaximal workloads compared with sea level, but peak blood lactate remain the same. Following continued exposure to hypoxia or altitude, blood lactate accumulation at submaximal work and peak blood lactate levels are paradoxically reduced compared with those at sea level. It has recently been shown, however, that, if the exposure to altitude is sufficiently long, blood lactate responses return to those seen at sea level or during acute hypoxia. Thus, to evaluate the 'lactate paradox' phenomenon in relation to time spent at altitude, five Danish lowland climbers were studied at sea level, during acute exposure to hypoxia (10% O2 in N2) and 1, 4 and 6 weeks after arrival in the basecamp of Mt Everest (approximately 5400 m, Nepal). Basecamp was reached after 10 days of gradual ascent from 2800 m. Peak blood lactate levels were similar at sea level (11.0 +/- 0.7 mmol L-1) and during acute hypoxia (9.9 +/- 0.3 mmol L-1), but fell significantly after 1 week of acclimatization to 5400 m (5.6 +/- 0.5 mmol L-1) as predicted by the 'lactate paradox'. After 4 weeks of acclimatization, peak lactate accumulation (7.8 +/- 1.0 mmol L-1) was still lower compared with acute hypoxia but higher than that seen after 1 week of acclimatization. After 6 weeks of acclimatization, 2 days after return to basecamp after reaching the summit or south summit of Mt Everest, peak lactate levels (10.4 +/- 1.1 mmol L-1) were similar to those seen during acute hypoxia. Therefore, these results suggest that the 'lactate paradox' is a transient metabolic phenomenon that is reversed during a prolonged period of exposure to severe hypoxia of more than 6 weeks.

Acclimatization↗
PubMed2003

Effect of mutations at Glu160 and Val198 on the thermostability of lactate oxidase.

We have obtained two types of thermostable mutant lactate oxidase - one that exhibited an E-to-G point mutation at position 160 (E160G) through error-prone PCR-based random mutagenesis, and another that exhibited an E-to-G mutation at position 160 and a V-to-I mutation at position 198 (E160G/V198I) through DNA shuffling-based random mutagenesis - both of which we have previously reported. Our molecular modeling of lactate oxidase suggests that the substitution of G for E at position 160 reduces the electrostatic repulsion between the negative charges of E160 and E130 in the (beta/alpha)8 barrel structure, but a thermal-inactivation experiment on the five kinds of single-mutant lactate oxidase at position 160 (E160A, E160Q, E160H, E160R, and E160K) showed that the side-chain volume of the amino acid at position 160 mainly contributes to the thermostability of lactate oxidase. We also produced V198I single-mutant lactate oxidase through site-directed mutagenesis, and analysed the thermostability of wild-type, V198I, E160G, and E160G/V198I lactate oxidase enzymes. The half-life of E160G/V198I lactate oxidase at 70 degrees C was about three times longer than that of E160G lactate oxidase, and was about 20 times longer than that of wild-type lactate oxidase. In contrast, the thermostability of the V198I lactate oxidase was almost identical to that of wild-type lactate oxidase. This indicates that the V198I mutation alone does not affect lactate oxidase thermostability, but does affect it when combined with the E160G mutation.

Amino Acid Sequence↗
PubMed2006

Lactate distribution in the blood compartments of sickle cell trait carriers during incremental exercise and recovery.

Whether or not whole blood lactate concentration is the same during a ramp exercise test in subjects with sickle cell trait (AS) as in normal subjects remains a point of controversy in the literature. Some studies have shown that the ability to produce or clear circulating lactate might differ between AS and subjects with normal haemoglobin (AA). If this is indeed so, the lactate distribution in the blood compartments should also differ. To test this hypothesis, lactate concentrations in the whole blood, plasma and red blood cells of AS and AA were compared at rest and in response to exercise. Eight AS and 8 AA performed an incremental exercise test. Whole blood, plasma and red blood cell lactate concentrations, the red blood cell : plasma lactate concentration ratio, the plasma-to-red blood cell lactate gradient, haematocrit and cardiorespiratory variables were analysed at rest and during an incremental exercise test and active recovery. Maximal oxygen uptake and ventilatory thresholds were similar in the two groups. No significant difference in whole blood, plasma or red blood cell lactate concentrations was observed between the two groups at rest, during exercise, or during the immediate recovery. Neither the red blood cell : plasma lactate concentration ratio nor the plasma-to-red blood cell lactate gradient differed between groups. Lactate distribution in the blood compartments did not differ between the two groups and this finding suggests that lactate production and/or clearance is quite similar during exercise in AS and AA.

Adult↗
PubMed1997

High serum D-lactate in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: As abnormally high serum D-lactate levels may cause neurological impairment, we determined whether patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with lactate-containing fluids have increased serum D-lactate concentrations. METHODS: D- and L-lactate concentrations were determined in peritoneal dialysis fluids and in serum from control subjects (n = 10), haemodialysis patients (n = 10), and CAPD patients (n = 30) before and after 1 h of dialysis. RESULTS: We found the median D-lactate concentration in Dianeal CAPD fluid to be 26 mM (range 19-27), whereas it was less than 0.5 mM in DPCA2 fluid. Control, haemodialysis, and CAPD (DPCA2) patient median serum D-lactate concentrations were below 0.07 mM. However, CAPD (Dianeal) patient serum D-lactate concentrations were 4-fold higher than controls (P < 0.0001), at 0.28 mM, an hour after instillation of D-lactate-containing fluid. Three patients, whose serum D-lactate averaged 0.59 mM, were found to have D-lactate concentrations at 0.22 mM after overnight cessation of dialysis. CONCLUSION: We conclude that CAPD with D-lactate-containing fluids raises serum D-lactate to abnormal levels.

Adult↗
PubMed2001

The hepatosplanchnic area is not a common source of lactate in patients with severe sepsis.

OBJECTIVE: To investigate the role of the splanchnic region in the hyperlactatemia of septic patients. DESIGN: Prospective, observational study. SETTING: Thirty-one-bed mixed medicosurgical intensive care unit. PATIENTS: Ninety invasively monitored and mechanically ventilated patients with severe sepsis. MEASUREMENTS AND MAIN RESULTS: Splanchnic lactate balance was measured in all patients. Splanchnic blood flow was determined by using the primed continuous indocyanine green infusion technique in 69 patients. In 71 patients, gastric mucosal Pco2 and the Pco2 gap (the difference between gastric and arterial Pco2) also were determined by using gas tonometry with an automated gas analyzer. In each patient, arterial, mixed-venous, and hepatic venous blood samples were obtained to determine hemoglobin oxygen saturations and lactate concentrations. Arterial and hepatic venous lactate concentrations were determined in triplicate and were averaged, and the arterial hepatic venous difference in lactate and lactate consumption were calculated. The splanchnic region produced lactate in only six of the 90 patients. Mean arterial pressure, cardiac index, arterial lactate, hepatic venous oxygen saturation, and catecholamine use were similar in the six patients with splanchnic lactate production and in the 84 others. The arterial hepatic venous differences in lactate and splanchnic lactate consumption were related directly to arterial lactate concentrations (y = 0.073x + 0.209, r(2) =.06, p <.05, and y = 0.06x + 0.183, r(2) =.08, p <.05, respectively) but were not related to Pco2 gap, to the gradient between mixed-venous and hepatic venous oxygen saturations, or to bilirubin concentrations. CONCLUSIONS: Splanchnic lactate release is uncommon in septic patients, even when hyperlactatemia is severe.

APACHE↗
PubMed1998

Lactate influx into red blood cells from trained and untrained human subjects.

PURPOSE: The purpose of this study was to compare the fractional contributions of the three pathways of lactate transport (band 3 system, nonionic diffusion, and monocarboxylate pathway) into red blood cells (RBC) from trained and untrained humans. METHODS: Blood samples were obtained from 19 male subjects: 5 untrained, 5 aerobically-trained, 5 competitive collegiate cross-country runners, and 4 competitive collegiate sprinters. The influx of lactate into the RBC was measured by a radioactive tracer technique using [14C]lactate. Discrimination of each pathway of lactate transport was achieved by using PCMBS (1 mM) to block the monocarboxylate pathway and DIDS (0.2 mM) to block the band 3 system. Nonionic diffusion was calculated as the difference between total lactate influx and the sum of band 3 and monocarboxylate lactate influx. RESULTS: Total lactate influx into the RBC from the more aerobic individuals (trained subjects and cross-country runners) was significantly faster at 1.6 mM lactate concentration ([La]) as compared with the influx into RBC of the untrained subjects. Total influx of lactate was significantly higher (P < 0.05) in the RBC from the sprinters as compared with that in the RBC from the untrained subjects at 41 mM [La]. There were no significant differences among the four groups with regard to the total influx of lactate at 4.1, 8.1, and 20 mM [La]. In general, the percentage of total lactate influx accounted for by each of the three parallel pathways at 1.6, 8.1, and 41.0 mM [La] was not different among the four groups of subjects. CONCLUSIONS: Overall, the groups were more similar than different with regard to RBC lactate influx.

Adult↗
PubMed2003

Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism.

UNLABELLED: The purpose of this study was to determine if the relationship between abnormalities in glucose, lactate, and oxygen metabolism were predictive of neurologic outcome after moderate or severe head injury, relative to other known prognostic factors. Serial assessments of the cerebral metabolic rates for glucose, lactate, and oxygen were performed using a modified Kety-Schmidt method. In total, 31 normal control subjects were studied once, and 49 TBI patients (mean age 36+/-16 years, median GCS 7) were studied five times median per patient from postinjury days 0 to 9. Univariate and multivariate analyses were performed. Univariate analysis showed that the 6-month postinjury Glasgow Outcome Scale (GOS) was most strongly associated with the mean cerebral metabolic rate of oxygen (CMRO2) (P = 0.0001), mean arterial lactate level (P = 0.0001), mean arterial glucose (P = 0.0008), mean cerebral blood flow (CBF), (P = 0.002), postresuscitation GCS (P = 0.003), and pupillary status (P = 0.004). Brain lactate uptake was observed in 44% of all metabolic studies, and 76% of patients had at least one episode of brain lactate uptake. By dichotomized GOS, patients achieving a favorable outcome (GOS 4-5) were distinguished from those with an unfavorable outcome (GOS1-3) by having a higher CMRO2 (P = 0.003), a higher rate of abnormal brain lactate uptake relative to arterial lactate levels (P = 0.04), and lesser degrees of blood-brain barrier damage based on CT findings (P = 0.03). CONCLUSIONS: During the first 6 days after moderate or severe TBI, CMRO2 and arterial lactate levels are the strongest predictors of neurologic outcome. However, the frequent occurrence of abnormal brain lactate uptake despite only moderate elevations in arterial lactate levels in the favorable outcome patients suggests the brain's ability to use lactate as a fuel may be another key outcome predictor. Future studies are needed to determine to what degree nonglycolytic energy production from alternative fuels such as lactate occurs after TBI and whether alternative fuel administration is a viable therapy for TBI patients.

Adult↗
PubMed2002

Measurement of interstitial lactate during hypoxia-induced dilatation in isolated pressurised porcine coronary arteries.

Lactate is formed in the coronary arterial wall and in the myocardium as a consequence of ischaemia and infarction. We combined direct measurement of coronary artery diameter and interstitial arterial wall lactate concentration ex vivo in order to ascertain the possible role of lactate in hypoxia-induced vasodilatation. The wall of porcine coronary arteries, precontracted during an intraluminal pressure of 40 mmHg by addition of prostaglandin F2alpha, was cannulated using a microdialysis catheter, and exposed to hypoxia for 60 min, followed by 45 min of reoxygenation. The exchange fraction of [14C]lactate over the microdialysis membrane increased from 0.38 +/- 0.04 to 0.52 +/- 0.05 (P < 0.001) during the study period. Coronary artery diameter increased by 15.5 +/- 2.0 % (n = 20) during hypoxia (P < 0.001, compared to normoxic controls) and interstitial lactate concentration rose from 1.07 +/- 0.21 to 2.50 +/- 0.40 mmol x l(-1) during hypoxia (P < 0.01) and was unchanged in controls. The increase in coronary artery diameter correlated with the increase in interstitial lactate concentration in the period between 30 and 60 min of hypoxia (r = 0.62; P = 0.02). Dichloroacetate (10(-5) M), an agent that reduces lactate generation by activating pyruvate dehydrogenase, abolished hypoxia-induced lactate production, but caused a further increase in coronary arterial diameter (30.2 +/- 4.4 %, n = 9; P < 0.001 vs. hypoxia and no dichloroacetate). Under control conditions, the addition of L-lactate (10(-3)-10(-2) M) increased dose-dependently coronary arterial diameter by 22.0 +/- 4.2 % (n = 5) and interstitial lactate concentration from 0.52 +/- 0.04 to 5.70 +/- 0.66 mmol x l(-1) (P < 0.001). There was a correlation between the increase in coronary artery diameter and interstitial lactate concentration (r = 0.60; P = 0.02). The present observations represent the first direct measurements of metabolites by microdialysis in a blood vessel wall. The lactate concentration may affect, but is not essential for, hypoxia-induced vasodilatation in porcine coronary arteries.

Animals↗
PubMed2002

Similar carbohydrate but enhanced lactate utilization during exercise after 9 wk of acclimatization to 5,620 m.

We hypothesized that reliance on lactate as a means of energy distribution is higher after a prolonged period of acclimatization (9 wk) than it is at sea level due to a higher lactate Ra and disposal from active skeletal muscle. To evaluate this hypothesis, six Danish lowlanders (25 +/- 2 yr) were studied at rest and during 20 min of bicycle exercise at 146 W at sea level (SL) and after 9 wk of acclimatization to 5,260 m (Alt). Whole body glucose Ra was similar at SL and Alt at rest and during exercise. Lactate Ra was also similar for the two conditions at rest; however, during exercise, lactate Ra was substantially lower at SL (65 micro mol. min(-1). kg body wt(-1)) than it was at Alt (150 micro mol. min(-1). kg body wt(-1)) at the same exercise intensity. During exercise, net lactate release was approximately 6-fold at Alt compared with SL, and related to this, tracer-calculated leg lactate uptake and release were both 3- or 4-fold higher at Alt compared with SL. The contribution of the two legs to glucose disposal was similar at SL and Alt; however, the contribution of the two legs to lactate Ra was significantly lower at rest and during exercise at SL (27 and 81%) than it was at Alt (45 and 123%). In conclusion, at rest and during exercise at the same absolute workload, CHO and blood glucose utilization were similar at SL and at Alt. Leg net lactate release was severalfold higher, and the contribution of leg lactate release to whole body lactate Ra was higher at Alt compared with SL. During exercise, the relative contribution of lactate oxidation to whole body CHO oxidation was substantially higher at Alt compared with SL as a result of increased uptake and subsequent oxidation of lactate by the active skeletal muscles.

Acclimatization↗
PubMed2000

Prandial lactate infusion inhibits spontaneous feeding in rats.

To investigate the acute effects of lactate on spontaneous feeding, we infused lactate in the hepatic portal vein (0.5, 1.0, and 1.5 mmol lactate/meal) or in the vena cava (1.0 and 1.5 mmol lactate/meal) of ad libitum-fed rats during their first spontaneous nocturnal meal. Infusions (5 min, 0.1 ml/min) were remotely controlled, and a computerized feeding system recorded meal patterns. In separate crossover tests, meal size decreased independent of the infusion route after 1.0 and 1.5 mmol but not after 0.5 mmol lactate. The subsequent intermeal interval (IMI) tended to decrease only after vena cava infusion of 1.0 mmol lactate. The size of the second nocturnal meal increased after the 1.0 mmol lactate infusion. Hepatic portal infusion of 1.5 mmol lactate increased the satiety ratio [subsequent IMI (min)/meal size (g)] by 175%, which was higher than the insignificant 43% increase after vena cava infusion. Hepatic portal infusion of 1.5 mmol lactate also increased systemic plasma lactate but not glucose concentration at 1 min after the end of infusion. The results are consistent with the idea that meal-induced increases in circulating lactate play a role in the control of meal size (satiation). Moreover, the results suggest that lactate also contributes to postprandial satiety and that the liver is involved in this effect. The exact mechanisms of lactate's inhibitory effects on feeding and the site(s) where lactate acts to terminate meals remain to be identified.

Animals↗
PubMed2005

Faster lactate transport across red blood cell membrane in sickle cell trait carriers.

The physical and physiological behavior of sickle cell trait carriers (AS) is somewhat equivocal under strenuous conditions, although this genetic abnormality is generally considered to be a benign disorder. The occurrence of incidents and severe injuries in AS during exercise might be explained, in part, by the lactic acidosis due to a greater lactate influx into AS red blood cells (RBCs). In the present study, the RBC lactate transport activity via the different pathways was compared between AS and individuals with normal hemoglobin (AA). Sixteen Caribbean students, nine AS and seven AA, performed a progressive and maximal exercise test to determine maximal oxygen consumption. Blood samples were obtained at rest to assess haematological parameters and RBC lactate transport activity. Lactate influxes [total lactate influx and monocarboxylate transporter (MCT-1)-mediated lactate influx] into erythrocytes were measured at four external [14C]-labeled lactate concentrations (1.6, 8.1, 41, and 81.1 mM). The two groups had similar maximal oxygen consumption. Total lactate influx and lactate influx via the MCT-1 pathway were significantly higher in AS compared with AA at 1.6, 41, and 81.1 mM. The maximal lactate transport capacity for MCT-1 was higher in AS than in AA. Although AS and AA had the same maximal aerobic physical fitness, the RBCs from the sickle cell trait carriers took up more lactate at low and high concentrations than the RBCs from AA individuals. The higher MCT-1 maximal lactate transport capacity found in AS suggests greater content or greater activity of MCT-1 in AS RBC membranes.

Adult↗
PubMed2006

Lactate, not glucose, up-regulates mitochondrial oxygen consumption both in sham and lateral fluid percussed rat brains.

OBJECTIVE: Failure of energy metabolism after traumatic brain injury may be a major factor limiting outcome. Although glucose is the primary metabolic substrate in the healthy brain, the well documented surge in tissue lactate after traumatic brain injury suggests that lactate may provide an energy need that cannot be met by glucose. We hypothesized, therefore, that administration of lactate or the combination of lactate and supraphysiological oxygen may improve mitochondrial oxidative respiration in the brain after rat fluid percussion injury. We measured oxygen consumption (VO2) to determine what effects glucose, lactate, oxygen, and the combination of lactate and oxygen have on mitochondrial respiration in both injured and uninjured rat brain tissue. METHODS: Anesthetized Sprague-Dawley rats were intubated and ventilated with either 0.21 or 1.0 fraction of inspired oxygen (FIO2). Brain tissue from acute sham animals was subjected in vitro to 1.1 mM, 12 mM and 100 mM concentrations of glucose and L-lactate. In another group, injury (fluid percussion injury of 2.5 +/- 0.02 atmospheres) was induced over the left hemisphere. The VO2 of mug amounts of brain tissues were measured in a microrespirometry system (Cartesian diver). RESULTS: The VO2 was found to be independent of glucose concentrations, but dose-dependent for lactate. Moreover, the lactate dependent VO2s were all significantly higher than those generated by glucose. Injured rats on FIO2 0.21 had brain tissue VO2 rates that were significantly lower than those of shams or preinjury levels. In injured rats treated with FIO2 1.0, the reduction in VO2 levels was prevented. Injured rats that received an intravenous infusion of 100 mM lactate had VO2 rates that were significantly higher than those obtained with FIO2 1.0. Combined treatment further boosted the lactate generated VO2 rates by approximately 15%. CONCLUSION: Glucose sustains mitochondrial respiration at a low level "fixed" rate because, despite increasing its concentration nearly 100-fold, it cannot up-regulate VO2 after fluid percussion injury. Lactate produces a dose-dependent VO2 response, possibly enabling mitochondria to meet the increased energy needs of the injured brain.

Animals↗
PubMed2006

Rapid decrease in plasma D-lactate as an early potential predictor of diminished 28-day mortality in critically ill septic shock patients.

BACKGROUND: Splanchnic ischemia plays a major role in the development of organ failure during septic shock. Plasma D-lactate has been proposed as a better marker of splanchnic hypoperfusion than L-lactate. We studied the prognostic ability of plasma D- and L-lactate levels. METHODS: A prospective study was performed in an intensive care unit and included patients with septic shock. Two samples for plasma D- and L-lactate determination were collected: the first within 6 h after the patient met the criteria for septic shock (day 1) and the second 24 h later (day 2). RESULTS: In univariate analysis, day 1 plasma D- and L-lactate values were associated with 28-day mortality. For plasma D- and L- lactate, the area under the receiver operating characteristic curve was 0.68+/-0.09 and 0.84+/-0.07 on day 1 (p=0.09), and 0.74+/-0.10 and 0.90+/-0.07 on day 2 (p=0.06), respectively. In survivors, D-lactate levels decreased between day 1 and day 2 (p=0.03), but L-lactate did not (p=0.29). In septic shock patients, plasma D- and L-lactate levels reliably discriminate between survivors and non-survivors. The prognostic ability of plasma L-lactate was better than that of plasma D-lactate. CONCLUSION: A rapid decrease in plasma D-lactate during the course of septic shock could indicate reduced 28-day mortality.

Aged↗