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PubMed1985

Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: a new approach for investigating human myocardial metabolism during ischemia.

Simultaneous lactate production and extraction have been previously demonstrated in the myocardium in patients with coronary artery disease. To quantitate this lactate production and determine its source, dual carbon-labeled isotope experiments were performed. L-[1,2,3-13C3] lactate and D-[6-14C] glucose were infused in 10 patients with significant coronary artery disease. Metabolic samples were obtained at rest and during atrial pacing. Despite net chemical myocardial lactate extraction in the 10 patients at rest and no evidence of clinical ischemia, the L-[1,2,3-13C3] lactate analysis demonstrated that lactate was being released by the myocardium. During atrial pacing, seven patients did not develop clinical symptoms of ischemia, and the chemical lactate analysis showed net lactate extraction. However, tracer analysis demonstrated that there was a significant increase in the lactate released during atrial pacing (from 6.9 +/- 2.3 to 16.2 +/- 10.1 mumol/min) (p less than 0.05). In these seven patients, circulating glucose was the source of 23 +/- 15% of the lactate released at rest, and there was no significant change during pacing. The remaining three patients had mild chest pain and net chemical lactate production during pacing. Lactate release detected by the tracer increased from 5.7 +/- 3.0 mumol/min at rest to 50.9 +/- 16.8 mumol/min during pacing (p less than 0.01). In these patients, the contribution of glucose to lactate production increased significantly during pacing-induced clinical ischemia from 25 +/- 22 to 67 +/- 14% (p less than 0.005). Thus, dual carbon-labeled isotopic experiments are powerful tools for investigating myocardial metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1971

Lactate production in the perfused rat liver.

1. In aerobic conditions the isolated perfused liver from well-fed rats rapidly formed lactate from endogenous glycogen until the lactate concentration in the perfusion medium reached about 2mm (i.e. the concentration of lactate in blood in vivo) and then production ceased. Pyruvate was formed in proportion to the lactate, the [lactate]/[pyruvate] ratio remaining between 8 and 15. 2. The addition of 5mm- or 10mm-glucose did not affect lactate production, but 20mm- and 40mm-glucose greatly increased lactate production. This effect of high glucose concentration can be accounted for by the activity of glucokinase. 3. The perfused liver released glucose into the medium until the concentration was about 6mm. When 5mm- or 10mm-glucose was added to the medium much less glucose was released. 4. At high glucose concentrations (40mm) more glucose was taken up than lactate and pyruvate were produced; the excess of glucose was probably converted into glycogen. 5. In anaerobic conditions, livers of well-fed rats produced lactate at relatively high rates (2.5mumol/min per g wet wt.). Glucose was also rapidly released, at an initial rate of 3.2mumol/min per g wet wt. Both lactate and glucose production ceased when the liver glycogen was depleted. 6. Addition of 20mm-glucose increased the rate of anaerobic production of lactate. 7. d-Fructose also increased anaerobic production of lactate. In the presence of 20mm-fructose some glucose was formed anaerobically from fructose. 8. In the perfused liver from starved rats the rate of lactate formation was very low and the increase after addition of glucose and fructose was slight. 9. The glycolytic capacity of the liver from well-fed rats is equivalent to its capacity for fatty acid synthesis and it is pointed out that hepatic glycolysis (producing acetyl-CoA in aerobic conditions) is not primarily an energy-providing process but part of the mechanism converting carbohydrate into fat.

Animals↗
PubMed1988

Insulin, dexamethasone and their interactions in the control of glucose metabolism in adipose tissue from lactating and nonlactating sheep.

1. Lactation results in decreased glucose and acetate utilization and increased lactate output by sheep adipose tissue. 2. The ability of insulin to stimulate acetate uptake was lost in adipose tissue from lactating sheep, whereas both the response and the sensitivity (ED50) for insulin for stimulation of glucose conversion into products other than lactate were decreased. These impairments were partly restored by prolonged incubation of adipose tissue for 48 h. 3. The ability of insulin to stimulate lactate output was not altered by lactation. 4. Dexamethasone inhibited glucose uptake, lactate output and glycerol output in adipose tissue from both non-lactating and lactating sheep, with an ED50 of about 1 nM. Dexamethasone inhibited acetate uptake by adipose tissue from non-lactating sheep, but this effect was not observed with adipose tissue from lactating sheep. 5. Dexamethasone inhibited the stimulation of glucose uptake at all concentrations of insulin used; the effect varied with insulin concentration and resulted in an accentuation of the insulin dose-response curve. The insulin dose-response curve in the presence of dexamethasone was muted during lactation. 6. The overall effect of these adaptations is to ensure that glucose and acetate utilization by adipose tissue after an insulin surge is diminished during lactation.

Adipose Tissue↗
PubMed1983

Does the gas exchange anaerobic threshold occur at a fixed blood lactate concentration of 2 or 4 mM?

The anaerobic threshold (theta an) is defined as the VO2 at which blood lactate concentration [lactate] begins to systematically increase (lactate "break point") during incremental exercise. Numerous studies have shown that gas exchange break points at the anaerobic threshold correlate highly (r congruent to 0.90) with the lactate break point. Recently, it has been suggested that the anaerobic threshold occurs at a fixed [lactate] of 2 mM or 4 mM. We therefore compared the gas exchange theta an to the three lactate criteria (break point, 2 mM, and 4 mM) for theta an estimation. Fourteen subjects performed an incremental cycle ergometer test. Ventilation and gas exchange were computed every 30 s. During the same 30-s intervals, venous blood was sampled for [lactate]. Four criteria were used for theta an determination: (1) systematic increase in VE/VO2, without a concomitant increase in VE/VCO2; (2) lactate break point; (3) 2 mM [lactate]; and (4) 4 mM [lactate]. Relative to the gas exchange criterion (i.e., #1), theta an was higher by 44, 280, and 1028 ml X min-1 for the three lactate criteria, respectively; the last two being significantly different (P less than 0.05). Thus, the anaerobic threshold discerned from gas exchange or the lactate break point does not correspond with a fixed, absolute [lactate] of 2 mM or 4 mM.

Adult↗
PubMed1994

Maternal protein reserves and their influence on lactational performance in rats.

To determine the contribution of tissue protein reserves to lactational performance, multiparous female Sprague-Dawley rats were mated, caged individually and offered a diet high in protein (215 g crude protein (N x 6.25; CP)/kg dry matter (DM); H) ad lib. until day 12 of gestation. Subsequently half the rats continued to receive diet H while the remainder were offered a diet low in protein (65 g CP/kg DM; L) until parturition. This treatment aimed to produce a difference in carcass protein at parturition. On day 1 of lactation females were allocated to either diet H or a low-protein diet (90 g CP/kg DM; L2) offered until day 13 of lactation, giving four lactation treatment groups HH, HL2, LH and LL2. Groups of females were slaughtered on days 2 and 12 of gestation and days 1 and 13 of lactation and carcass and major organs were analysed. Weight gain of standardized litters was used as an indicator of lactational performance. Maternal carcass protein contents at parturition were 43.5 (SE 1.2) and 38.7 (SE 0.8) g (P < 0.01) for diets H and L respectively. During lactation there was little change in carcass protein content of HH rats while LH rats appeared to replenish their depleted reserves. Food intake or lactational performance did not differ between these two groups. HL2 and LL2 rats lost carcass protein with HL2 rats losing more than LL2 rats (P < 0.05). Intake and lactational performance were reduced compared with that on diet H (P < 0.05) but for the first 6 d of lactation were both greater (P < 0.05) for diet HL2 than for diet LL2. All four groups showed a considerable loss of body fat during lactation which was not affected by diet. The ability of HL2 rats to catabolize more protein and consume more food allowed them to sustain a greater lactational performance. Previous maternal protein depletion had no influence on lactational performance as long as an adequate supply of dietary protein was provided.

Animals↗
PubMed1995

Relationship between blood lactate concentrations and ionized calcium, glucose, and acid-base status in critically ill and noncritically ill patients.

OBJECTIVE: To determine the relationships between circulating blood lactate concentrations and several biochemical variables including ionized calcium, glucose, pH, and acid-base status in critically ill and noncritically ill patients. DESIGN: A prospective, cohort study. SETTING: The critical care research laboratory, intensive care unit (ICU), emergency room (ER), and general ward of a 466 bed university-affiliated hospital. PATIENTS: Three-hundred thirty-four critically ill and noncritically ill patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Circulating blood lactate concentrations, ionized calcium concentrations, blood glucose, pH, and base deficit values were simultaneously determined in blood samples from various patient populations. Descriptive data and physiologic parameters were also recorded. Circulating lactate and ionized calcium determinations were performed simultaneously in 334 whole blood samples from 334 subjects. There was neither a statistically significant nor clinically relevant correlation between circulating lactate concentrations and ionized calcium concentrations when lactate values were < or = 2 mmol/L (p = 0.8962, r2 = .01) or when lactate values were > 2 mmol/L (p = .3697, r2 = .09) in a heterogeneous patient population. Our study populations included five subject groups: a) nonhypotensive ICU patients (n = 93), b) nonhypotensive ER patients (n = 85), c) nonhypotensive general ward patients (n = 44), d) hypotensive patients from the ICU, ER, and general wards (n = 39), and e) normal controls (n = 73). There was neither a statistically significant nor clinically relevant correlation between circulating lactate concentrations and ionized calcium concentrations in each of the five populations studied for lactate values either < or = 2 mmol/L or > 2 mmol/L. We studied the relationship between circulating lactate concentrations and blood glucose concentrations (n = 334 patients), arterial pH and base deficit (n = 163 patients), and venous pH and base deficit (n = 171 patients). Statistically significant, but perhaps not clinically relevant correlations were observed when comparing circulating lactate values with blood glucose values (p = .0330, r2 = .12), arterial pH (p = .0007, r2 = .26) and base deficit from arterial specimens (p = .0014, r2 = .25). There were neither statistically significant nor clinically relevant correlations when comparing circulating lactate concentrations with venous pH (p = .9098, r2 = .01) or base deficit determined from venous blood specimens (p = .1365, r2 = .11). CONCLUSIONS: a) There is neither a statistically significant nor clinically relevant relationship between whole blood lactate concentrations and ionized calcium concentrations when studying patients with or without hyperlactatemia. b) Although there is a statistically significant correlation between circulating lactate concentrations and blood glucose concentrations, arterial pH or arterial base deficit, such associations do not appear to be clinically important.

Acid-Base Equilibrium↗
PubMed1990

Oxygen-dependent lactate utilization by Actinomyces viscosus and Actinomyces naeslundii.

Actinomyces viscosus and Actinomyces naeslundii were grown in chemostat cultures with glucose or lactate as the sole sources of energy. Growth on lactate was dependent on oxygen. Lactate was oxidised partly to acetic acid. As judged from the low carbon recoveries in acidic degradation products, it is concluded that a substantial part of the lactate was oxidised to carbon dioxide. Assuming that 1 ATP is generated in the transfer of an electron pair to oxygen, YATP values of 10-11 were calculated from the molar growth yield on lactate and product formation. Although all cell 3 test strains oxidised lactate, one strain could not grow on lactate as the sole source of energy. The rate of oxygen uptake with lactate as substrate was higher for cells grown aerobically than of cells grown anaerobically, indicating that lactate oxidation was induced by oxygen. It is reasonable to assume that lactate oxidation is mediated either by lactate dehydrogenase or lactate oxidase, but the pathway in Actinomyces sp. is not yet known. Lactate consumption may be an important trait of Actinomyces sp. that live in an environment limited in energy sources for most of the time.

Actinomyces↗
PubMed1996

Differential toxic effects of lactate and acetate on the metabolism of Streptococcus mutans and Streptococcus sanguis.

Experiments were conducted with Streptococcus mutans NCTC 10449 and Streptococcus sanguis ATCC 10556 to determine whether the acid end-products, lactate and acetate, were involved in the regulation of cellular growth and metabolism. The growth rate and culture biomass of both organisms was inhibited by the addition of lactate and acetate at concentrations as high as 200 mM to the cultures, although the final pH values of the lactate and acetate cultures were similar. In addition, the metabolic conversion of glucose to lactate was decreased by external lactate but stimulated by acetate. In spite of this, calculation of the yield of cell biomass per mole of ATP (YATP) showed that the yield of both organisms actually increased in the presence of added lactate, but decreased with acetate. This indicates that the two acids interacted with the cells of the organisms by different mechanisms. For both organisms, the final external undissociated lactic acid was relatively constant at concentrations between 0 and 200 mM added lactate, 24.9-32.5 mM for S. mutans and 8.0-11.5 mM for S. sanguis. On the other hand, the final concentration of undissociated acetic acid in the S. mutans cultures increased from 2.9 to 83.7 mM as the medium acetate concentration increased, and from 1.0 to 36.0 mM with the S. sanguis cultures. Counterflow experiments provided evidence for a lactate carrier in both S. mutans and S. sanguis, but an acetate carrier in these organisms could not be demonstrated. [14C]-lactate and [14C]-acetate were taken up into de-energized, chemostatgrown cells of S. mutans and S. sanguis in response to an artificially generated pH gradient but not by an imposed electrical gradient. Thus, under these conditions lactate uptake occurred via a symport process with only one proton. Growth of both organisms in the presence of increasing concentrations of acetate resulted in a small reduction (27%) in the transmembrane pH gradient (delta pH) as measured by the permeant acid, [14C]-salicylate. However, the uptake of [14C]-acetate for the estimation of delta pH revealed significant inhibition of the acetate concentration gradient in the presence external acetate, indicating that the cells expelled the acetate anion. The results indicate that, unlike acetate uptake, lactate transport by S. mutans and S. sanguis was strictly regulated via the lactate carrier in order to prevent excessive dissipation of the pH gradient. Clearly, the formation of acetate by oral streptococci is more problematic for cellular homeostasis than the formation of lactate.

Acetic Acid↗
PubMed2006

Ovarian activity and oestrous signs among group-housed, lactating sows: influence of behaviour, environment and production.

Animal welfare concerns require the development of housing systems that allow the animals to express their natural behaviour. One example of this is the group-housing system for lactating sows. The present study aimed at exploring ovarian activity in such a system. Thirty-eight sows farrowing individually outdoors during spring and summer, and indoors during autumn and winter, and group-housed in groups of four during weeks 3-7 of the lactation period, were monitored regarding reproductive functions, behaviour and production during their first to fourth lactation period. Average ovulation frequency during lactation was 47%. Only 50% of these ovulating cases were accompanied by a standing oestrus. Lactational ovulation frequency was higher in later parities (p < 0.001). Ovulation frequency was higher (p < 0.05) during winter (74%) and spring (69%), than during summer (10%) and autumn (23%). Occurrence of lactational ovulation was associated with some aspects of suckling behaviour and also with litter weight gain (p < 0.05). Forty-nine per cent of the lactational ovulations occurred during the seventh week of lactation. Timing of ovulation seemed positively (p = 0.08) associated with weight loss during lactation. Compared with the sows that were anoestrus during lactation, oestradiol-17beta values were higher (p < 0.05) only in the week before occurrence of lactational ovulation. Weaning-to-oestrous interval was prolonged (p < 0.05) among the sows that ovulated during lactation. The present study identifies several factors influencing ovarian activity among group-housed sows, thereby providing tools for the control of lactational ovulation in group-housing systems.

Animal Husbandry↗
PubMed1989

Postmortem human brain pH and lactate in sudden infant death syndrome.

Lactate and pH were measured in frontal and temporal cortex, cingulate gyrus, and caudate nucleus in brains from sudden infant death syndrome (SIDS) cases, control infants, and control adults. Both the lactate levels and the pH values were significantly correlated (p less than 0.001) between the four brain areas, whereas lactate and pH values were significantly correlated within each brain area (p less than 0.001) with a value of pH 7.2 for zero lactate. The lactate concentration in heart blood was significantly correlated with brain lactate (p less than 0.001). Adult sudden death cases (heart attacks) had low lactate and high pH values, whereas agonal state cases had high lactate and low pH values. Control infants who had died because of accidents also had low lactate and high pH values, but infants who might have been exposed to hypoxia before death had high lactate and low pH values. SIDS cases fell into two groups: the first, consisting of all victims over 30 weeks of age and about one-half to two-thirds of those aged less than 30 weeks, had low lactate and high pH values; the second group, consisting of about one-third to one-half of those less than 30 weeks old, had high lactate and low pH values. The changes in lactate levels and pH values indicate that the majority of SIDS cases had died suddenly, but that a sizeable minority had been exposed to hypoxia prior to death.

Brain↗
PubMed1993

Endurance training increases skeletal muscle lactate transport.

Lactate accumulation in skeletal muscle is reduced after a period of endurance training. Explanations for this phenomena include the increased oxidative capacity of the muscle, a reduction in lactate production, and increased lactate clearance. Muscle membrane transport of lactate can be seen to be a fundamental aspect of such clearance, and transmembrane lactate flux may well be an important aspect of the training response in skeletal muscle. Therefore, the lactate transport capacity in skeletal muscle sarcolemmal membranes in endurance-trained and sedentary rats was investigated. Training consisted of 6 weeks of progressively increased treadmill exercise. Twenty-four hours before being killed, both the trained and sedentary animals completed a brief exercise bout. Studies of lactate transport (zero-trans) were conducted using highly purified sarcolemmal vesicles. When low concentrations of L-lactate (1 mM) were used a 59.4% increase in lactate transport was observed (P < 0.05). However, when a high concentration of lactate (50 mM) was used no change in lactate transport was found (P > 0.05). Several interpretations are possible for these observations: (1) that there is an alteration in the Km but not the Vmax of the lactate transport system in skeletal muscle membranes; and (2) that specific changes occur in selected isoforms of the lactate transport protein which may co-exist in muscle.

Animals↗
PubMed2002

Lactate transport in red blood cells by monocarboxylate transporters.

The lactate transport activity of red blood cells (RBC) varies widely among different species; in equine RBC, the activity of the main lactate carrier, H+-monocarboxylate co-transporter (MCT), is distributed bimodally. The influence of lactate transport activity is measurable in vivo; after maximal exercise, the RBC lactate concentration in horses with high (HT) lactate transport activity is higher than in those with low (LT) activity. To study the expression of MCT in HT and LT horses, blood samples were taken from 10 horses at rest and after submaximal exercise. Blood and plasma lactate concentrations, lactate and pyruvate transport activities and the amounts of MCT1, MCT2 and MCT4 were measured. After exercise, RBC lactate concentration was higher in HT (n = 5) than in LT (n = 5) horses. At lactate concentrations of 0.25-30 mmol/l and at a pyruvate concentration of 1 mmol/l, transport activity was higher in HT horses. At a lactate concentration of 0.1 mmol/l, transport was similar. In Western blots, the signals for MCT1 and MCT2 were similar in both groups. The amount of CD147, a chaperone necessary for the activity of MCT1, was lower in LT horses. We suggest that MCT2 transports lactate at low concentrations, while MCT1 is needed at higher concentrations. MCT1 may be less active in LT horses and, therefore, during exercise their capacity to take up lactate is low. Further studies are needed to show whether the differences in lactate influx in RBC affect the function of erythrocytes or the performance capacity of horses.

Animals↗
PubMed1976

The utilization of glucose and production of lactate by in vitro preparations of rat small intestine: effects of vascular perfusion.

1. The rate of metabolism of glucose to lactate has been measured in a number of non-vascularly perfused preparations of rat jejunum in vitro. The glucose and lactate metabolism was measured simultaneously and under conditions such that the uptake of glucose and the appearance of lactate were linearly related to time. 2. It is found that there is no difference between the rates at which rings of rat jejunum utilize glucose during the first 45 min of anaerobic or aerobic incubation. During the first 15 min of incubation between 60-70% of the metabolized glucose was converted to lactate under aerobic conditions; this value increased to 80-90% during the subsequent 30 min. During the period 0-15 min of incubation, lactate production was found to be higher under anaerobic than under aerobic conditions but after this initial period the rate of lactate production was the same under aerobic and anaerobic conditions. 3. For segments of rat jejunum, maintained in vitro by the recirculation of nutrient fluid through the intestinal lumen, neither the rate of production of lactate, nor the utilization of glucose, was stimulated if the preparation was maintained under anaerobic rather than aerobic conditions. The direct delivery of gas into the intestinal lumen in the form of a stream of bubbles (segmented circulation) reduced both the utilization of glucose and the production of lactate under aerobic conditions. However, not effect on glucose metabolism was observed under anaerobic conditions. The finding of a Pasteur effect with the segmented-circulated preparation, but not with the simple recirculated preparation, is associated with lower rate of aerobic lactate production in the former preparation. Reasons are given for supposing that under conditions of segmented circulation, the luminal compartment is better stirred, thereby increasing access of O2 to the tissue. 4. A preparation of rat small intestine perfused through the vascular bed is described. With this preparation the rate of glucose utilization is significantly lower than that for recirculated preparations and the rate of lactate production is substantially less than that of the other preparations studied. 5. With the preparation perfused through the vascular bed, and with glucose, 10 mM, present only in the vascular medium the addition of erythrocytes to the vascular infusate causes a significant reduction in both glucose utilization and in the rate of lactate production. The addition of erythrocytes to produce an haematocrit of 40% (v/v) causes a greater reduction in glucose utilization and lactate production than is found for an haematrocrit of 15%. About 10% of the lactate produced appears in the luminal contents. With an haematocrit of 15%, the O2 consumption of the whole wall of the jejunum was found to be 6-4 mumole O2 g dry wt.-1 min-1, equivalent of a value for the Q02 of 8-6 mul. O2 mg druwy wt.-1 hr-1. The uptake of O2 was almost entirely from the vascular infusate. 6...

Aerobiosis↗
PubMed1988

A microelectrode study of the mechanisms of L-lactate entry into and release from frog sartorius muscle.

1. Changes in intracellular pH and intracellular anion levels were monitored in frog sartorius muscle fibres during exposure to extracellular L-lactate, using ion-sensitive microelectrodes. 2. Resting intracellular pH (pHi) in 20 mmol l-1 HEPES buffer was 7.18 +/- 0.015 (S.E. of mean, n = 62). Exposure to an extracellular solution at pH 6.5 buffered with 20 mmol l-1 3-(N-morpholino)propanesulphonic acid (MOPS) resulted in a slow intracellular acidification. 3. A reversible decrease in pHi and an increase in intracellular anion levels was observed when L-lactate replaced chloride in equimolar amounts. The increase in intracellular anion level is consistent with intracellular accumulation of L-lactate ion. 4. The rate and steady-state change in pHi and anion level was a function of both extracellular pH and L-lactate concentration, providing evidence for the coupled movement of lactate and proton equivalents. 5. The initial rate of uptake of L-lactate, as measured by the change of pHi, was a non-linear function of the extracellular L-lactate concentration at extracellular pH 6.8 and 7.35. 6. No saturation was observed with concentrations of L-lactate between 5 and 60 mmol l-1 at pH 7.35 and 2.5 and 40 mmol l-1 at pH 6.8. 7. The non-linear relationship between the initial rate of change in pHi and extracellular L-lactate was well fitted by a curve defining uptake as the sum of a carrier process displaying Michaelis-Menten kinetics and a passive diffusion component. The apparent Km of the carrier was 10 mmol l-1 at pHo 7.35 and 4 mmol l-1 at pHo 6.8. 8. The initial rate of change of pHi in the presence of L-lactate was significantly inhibited 39.1 +/- 6.2% by 2-5 mmol l-1 alpha-cyano-4-hydroxycinnamate (n = 9; P less than 0.05, paired t test). 9. alpha-Cyano-4-hydroxycinnamate had no detectable effect on the initial rate of change of pHi induced by propionate exposure. 10. The initial rate of change of pHi induced by L-lactate was not affected by 20-100 mumol l-1 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS). 11. We conclude that L-lactate crosses the membrane of the frog sartorius muscle with proton equivalents via (1) a carrier-mediated process, and (2) passive diffusion of lactic acid. In the physiological range of L-lactate concentrations and pH the transport process dominates.

Animals↗
PubMed1996

Mechanism of lactate-induced relaxation of isolated rat mesenteric resistance arteries.

1. The effects of the sodium salt of the weak acid lactate on tension and intracellular pH (pH1) were studied in rat mesenteric small arteries mounted on a wire myograph. Sodium lactate was substituted iso-osmotically for sodium chloride. 2. At a concentration of 50 mM, both L- and D-stereoisomers of lactate markedly relaxed arteries preconstricted with noradrenaline (NA) within 10 min. The concentration-response relationship for L-lactate showed that the NA contracture was relaxed by 50% at approximately 26 mM. L-Lactate did not, however, relax arteries preconstricted with high-K+(45 mM) solution. 3. L-Lactate did not alter extracellular pH (pHo) but caused a small but significant decrease in pH1, measured using the pH-sensitive fluorochrome, 2',7'-bis(carboxyethyl)-5-(6)-carboxyfluorescein (BCECF). Relaxation to L-lactate was unaffected when this change in pHi was offset by the simultaneous addition of NH4Cl to the solution. 4. Sodium pyruvate (50 mM) caused a significant intracellular acidosis but did not relax arteries preconstricted with NA. 5. L-Lactate-induced relaxations were unaffected by removal of the endothelium or when the synthesis of nitric oxide (NO) was inhibited by 10(-4) M N omega-nitro-L-arginine methyl ester (L-NAME). 6. The potassium channel blockers glibenclamide (10 microM), 4-aminopyridine (3 mM) and tetraethylammonium chloride (10 mM) did not affect L-lactate-induced relaxation in arteries preconstricted with NA. Inhibition of guanylate cyclase with Methylene Blue, or cyclooxgenase with indomethacin, also did not affect relaxation to L-lactate. 7. The Rp stereoisomer of adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS), an analogue of cAMP which inhibits competitively stimulation of protein kinase A, reduced significantly L-lactate-induced relaxation at a concentration of 25 microM. Rp-cAMPS also significantly reduced forskolin-induced relaxation of the NA contracture. 8. It is concluded that L-lactate-induced relaxation in this vascular bed is pHi-1 endothelium-, and nitric oxide-independent. It is not mediated by inhibition of voltage-gated Ca2+ channels, opening of K+ channels, prostacylin or cyclic GMP. cAMP may however play a role in L-lactate-induced relaxation.

Animals↗
PubMed1978

Lactate metabolism in perfused rat lung.

Glucose utilization and lactate metabolism were studied in isolated rat lungs perfused with a Krebs-Henseleit bicarbonate buffer, pH 7.4, containing either [U-14C]lactate, [U-14C]glucose, or [U-14C]alanine. Glucose uptake showed an apparent Km of 4.7 mM and a Vmax of 107 mumol-g dry wt-1-h-1. Lactate production under these conditions showed a Vmax of 82.9 mumol-g dry wt-1-h-1. At high circulating lactate level (7 mM), the perfused lung showed an increased capacity to utilize [U-14C]lactate with preferential incorporation into lung lipids. At equal molar concentration (5 mM) [U-14C]lactate was preferentially incorporated over [U-14C]glucose. Addition of 5 mM lactate to the perfusion medium did not affect lactate production. Perfused lungs from fasted rats showed higher lactate production, with increased amounts of [U-14C]alanine converted to lactate by the perfused lung, indicating lactate can also be derived from noncarbohydrate sources. These data show that under aerobic conditions the perfused lung can produce and utilize lactate simultaneously, and lactate can serve as a potential substrate for lung lipids.

Animals↗
PubMed1989

Endurance training enhances lactate clearance during hyperlactatemia.

Constant infusions of cold molar lactate (178.0 +/- 1.6 mumol.kg-1.min-1), [U-14C]lactate (0.50 muCi/min), and [6-3H]glucose (0.5 muCi/min) were employed to study the effects of endurance training (running 1 h/day, at 38 m/min, 10% grade) on lactate clearance in resting, hyperlactatemic rats. Before infusion, resting blood lactate levels were not significantly different between controls, 1.10 +/- 0.04 mM, and trained animals, 1.16 +/- 0.04 mM. Lactate levels increased significantly during the infusion period, attaining steady-state mixed venous concentrations of 11.32 +/- 0.24 mM and 5.44 +/- 0.09 mM, respectively, for controls and trained animals. Lactate clearance rates, based on net lactate removal (i.e., not tracer-estimated lactate removal), were twofold greater in trained animals vs. controls, 33.0 +/- 0.7 and 15.4 +/- 0.4 ml.kg-1. min-1, respectively. Lactate specific activity values during the infusion period were not significantly different between controls, 22,243 +/- 236 dpm/mumol, and trained animals, 21,270 +/- 374 dpm/mumol, indicating similar endogenous dilution of the pyruvate-lactate pool. For both control and trained animals, essentially 100% of the 14C infused as lactate was recovered as either glucose or CO2; however, trained animals demonstrated a 25% greater rate of gluconeogenesis. At a given lactate production rate, trained animals maintain lower lactate levels through enhanced clearance via gluconeogenesis and oxidation.

Animals↗
PubMed1990

Role of cell type in net lactate removal by skeletal muscle.

Net lactate uptake and subsequent pathways for removal were studied in three rabbit skeletal muscle preparations of distinct fiber type composition, i.e., glycolytic (99.1 +/- 0.2% type IIb fibers), oxidative (97.5 +/- 0.6% type I fibers), and mixed (type I, IIa, and IIb fibers). Single-pass perfusions were carried out for 3 h in the presence of glucose, lactate, and [U-14C]lactate. Lactate levels, initially set at either 1 mM (n = 4/prep) or 2 mM (n = 4/prep), were elevated twice during the perfusion at 60 and 120 min. Net lactate uptake (mumol.100 g-1.min-1) was first observed in the oxidative preparation, 1.4 +/- 0.2, at an arterial lactate concentration of approximately 2.5 mM, whereas net lactate uptake in the glycolytic, 0.7 +/- 0.2, and mixed preparations, 7.0 +/- 0.5, was first observed at 4 mM. Net lactate balance, [14C]lactate removal, and 14CO2 release demonstrated strong linear correlations (r = 0.94-0.98) with arterial lactate concentration. To quantify the fate of [14C]lactate, preparations were perfused at a single elevated lactate concentration (approximately 8 mM) for 2 h. Oxidation was the primary means of disposal in the oxidative and mixed preparations, whereas glyconeogenesis dominated removal in the glycolytic preparation. The arterial lactate concentration at which a given muscle switches from net production to net removal, the rate of removal, and subsequent pathway(s) for disposal are a function of that muscle's fiber type composition.

Animals↗