Administration Of Sodium Lactate Research Articles

Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia

BackgroundSleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously.MethodsThe 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration.ResultsThe 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31+Glut1+ cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro.ConclusionsAffected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation.

Lactate increases stemness of CD8 + T cells to augment anti-tumor immunity

Lactate is a key metabolite produced from glycolytic metabolism of glucose molecules, yet it also serves as a primary carbon fuel source for many cell types. In the tumor-immune microenvironment, effect of lactate on cancer and immune cells can be highly complex and hard to decipher, which is further confounded by acidic protons, a co-product of glycolysis. Here we show that lactate is able to increase stemness of CD8+ T cells and augments anti-tumor immunity. Subcutaneous administration of sodium lactate but not glucose to mice bearing transplanted MC38 tumors results in CD8+ T cell-dependent tumor growth inhibition. Single cell transcriptomics analysis reveals increased proportion of stem-like TCF-1-expressing CD8+ T cells among intra-tumoral CD3+ cells, a phenotype validated by in vitro lactate treatment of T cells. Mechanistically, lactate inhibits histone deacetylase activity, which results in increased acetylation at H3K27 of the Tcf7 super enhancer locus, leading to increased Tcf7 gene expression. CD8+ T cells in vitro pre-treated with lactate efficiently inhibit tumor growth upon adoptive transfer to tumor-bearing mice. Our results provide evidence for an intrinsic role of lactate in anti-tumor immunity independent of the pH-dependent effect of lactic acid, and might advance cancer immune therapy.

Exogenous Lactate Intake Can Induce Muscle Synthesis in Rats

PurposeLactate had been recognized as fatigue substance during high intensity exercise. However, the lactate paradigm has changed in the last decades, and it was reconsidered as a potential factors of energy resource and muscle adaptation. Nevertheless, the effect of administration of exogenous lactate on muscle has not been elucidated, and it has been no molecular signaling study of the muscle synthesis over time after ingestion. Therefore, we aimed to investigate the effect of lactate on muscle synthesis on skeletal muscle, according to the different time intervals within 2 hours.MethodsMale rats were randomly assigned into one of following four timings that were sacrificed time after oral administration of sodium lactate (2 g/kg); 0 min (n = 8), 30 min (n = 8), 60 min (n = 8) and 120 min (n = 8). After administration lactate, rats were sacrificed and immediately obtained blood and skeletal muscle (plantaris). To determine the effect of lactate on muscle synthesis (Akt, mTOR) and degradation (MuRF1, atrogin‐1), we measured mRNA expression in plantaris by RT‐PCR, and analyzed blood parameters of lactate, insulin, IGF1, glycerol and glucose.ResultsThe results showed that, despite no significant differences in the hormone receptors for androgen and IGF1 associated with synthesis, Akt remained 1.5~2 fold higher after 30minutes, and mTOR was lower than the 30‐minute expression level but showed a high trend at 60 and 120 minutes. In muscle degradation factors, MuRF1 remained elevated after 30 minutes, but atrogin‐1 had no change. Lactate intake increased plasma lactate by about 3.2 mmol / L at 60 minutes and decreased insulin and IGF 1 after 30 minutes. Furthermore, plasma glycerol was increased at 120 min, but glucose has not changed within 2 hours.ConclusionIt is demonstrated in the present study that lactate administration contributes to increase muscle synthesis factors at 30 minutes, and it remained at high levels within 2 hours. Moreover, the reduction of insulin and IGF1, and the upregulation lactate confirmed that the administration of lactate might be similar to the blood response of the human body during low or moderate exercise. Therefore, our results suggest that lactate intake as a supplement has the potential to increase muscle synthesis and have a positive effect on muscle injury and recovery after exercise. Despite these results, because our study is acute intake and synergies with exercise are not identified, further research is required to investigate the long‐term administration of lactate and the effects of exercise on muscle synthesis.Support or Funding InformationThis work was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea(NRF‐2019S1A5A8033825)

Lactate Stimulates a Potential for Hypertrophy and Regeneration of Mouse Skeletal Muscle

The effects of lactate on muscle mass and regeneration were investigated using mouse skeletal muscle tissue and cultured C2C12 cells. Male C57BL/6J mice were randomly divided into (1) control, (2) lactate (1 mol/L in distilled water, 8.9 mL/g body weight)-administered, (3) cardio toxin (CTX)-injected (CX), and (4) lactate-administered after CTX-injection (LX) groups. CTX was injected into right tibialis anterior (TA) muscle before the oral administration of sodium lactate (five days/week for two weeks) to the mice. Oral lactate administration increased the muscle weight and fiber cross-sectional area, and the population of Pax7-positive nuclei in mouse TA skeletal muscle. Oral administration of lactate also facilitated the recovery process of CTX-associated injured mouse TA muscle mass accompanied with a transient increase in the population of Pax7-positive nuclei. Mouse myoblast-derived C2C12 cells were differentiated for five days to form myotubes with or without lactate administration. C2C12 myotube formation with an increase in protein content, fiber diameter, length, and myo-nuclei was stimulated by lactate. These observations suggest that lactate may be a potential molecule to stimulate muscle hypertrophy and regeneration of mouse skeletal muscle via the activation of muscle satellite cells.

The Harmful Effects of Hypertonic Sodium Lactate Administration in Hyperdynamic Septic Shock.

Hypertonic sodium lactate (HTL) expands intravascular volume and may provide an alternative substrate for cellular metabolism in sepsis. We compared the effects of HTL, hypertonic saline (HTS), 0.9% ("normal") saline (NS) and Ringer's lactate (RL) on hemodynamics, sublingual and renal microcirculation, renal, mesenteric and brain perfusion, renal and cerebral metabolism, and survival in anesthetized, mechanically ventilated, adult female sheep. Animals (7 in each group) were randomized to receive a bolus (over 15-min) of 3 mL/kg 0.5 M HTL, 3 mL/kg 3% HTS, 10.8 mL/kg NS, or 10.8 mL/kg RL at 2, 6, and 10 h after induction of fecal peritonitis, followed by 2-h infusions of 1 mL/kg/h (HTL/HTS groups) or 3.6 mL/kg/h (NS/RL groups). Animals also received RL and hydroxyethyl starch (ratio 1:1) titrated to maintain pulmonary artery occlusion pressure at baseline levels throughout the experiment. Animals were observed until their spontaneous death. Fluid balance was lower in the HTL and HTS groups than in the other groups from 4 h. Hemodynamic variables were similar among groups during the first 12 h, but thereafter the HTL group had more pronounced decreases in blood pressure and cardiac function. Sublingual and renal microcirculatory abnormalities occurred earlier in the HTL group. Kidney and brain perfusion decreased more rapidly in the HTL group. Median survival times were significantly shorter in the HTL (17 h) and NS (16 h) groups than in the HTS (22 h) or RL (20 h) groups (P = 0.0029). In conclusion, in an ovine model of septic shock, administration of HTL was associated with earlier onset impaired tissue perfusion and shorter survival time. These observations raise concerns about use of HTL in septic shock.

Adaptation of the Secretion of Aldosterone and Angiotensin II to Exercise in Rats.

Aldosterone is a mineralocorticoid produced by the zona glomerulosa (ZG) cells of the adrenal cortex. Previous studies have demonstrated that exercise is one of the stresses known to increase aldosterone production. Both potassium and angiotensin II levels in the plasma were correlated with aldosterone secretion during exercise, but the action mechanism is still unclear. In our in vivo study, male rats were catheterized via right jugular vein (RJV), and divided into four groups including water immersion, swim, lactate infusion (13 mg/kg/min) and pyruvate infusion (13 mg/kg/min) groups. Each group was treated for 10 min. Blood samples were collected at 0, 10, 15, 30, 60 and 120 min from RJV after administration. In an in vitro study, ZG cells from experimental rats were challenged by lactate (1-10 mM) with or without angiotensin II (10 nM) for 60 min. The levels of plasma angiotensin II and those of aldosterone in plasma and medium were measured by radioimmunoassay. Protein expressions in cell lysates were measured by immunoblotting assay. Ten min after exercise and lactate infusion, plasma levels of aldosterone and lactate were significantly higher than those in the control group. The level of angiotensin II was increased by swimming but not by lactate infusion. The levels of plasma sodium were increased whereas those of plasma potassium were decreased by swimming and infusion of sodium lactate or sodium pyruvate. The responses of plasma osmolality were synchronized with those of plasma sodium in the experimental animals. Administration of angiotensin II (10 nM) in vitro significantly increased aldosterone production. Sodium lactate (1-10 mM) alone did not alter the release of aldosterone. Co-incubation of angiotensin II (10 nM) with sodium lactate (10 mM) resulted in an increased production of aldosterone as compared with the group treated with angiotensin II alone. Administration of sodium lactate did not alter the protein expression of P450scc, but enhanced steroidogenic acute regulatory protein (StAR) expression in the presence of angiotensin II (10 nM) in ZG cells. These results demonstrated that short-time exercise led to the increase of aldosterone secretion, which is associated with the increased secretion of angiotensin II and the direct stimulatory effect of lactate on the action of angiotensin II in ZG cells. (poster)

Brain energy depletion in a rodent model of diffuse traumatic brain injury is not prevented with administration of sodium lactate

Lactate has been identified as an alternative fuel for the brain in situations of increased energy demand, as following a traumatic brain injury (TBI). This study investigates the effect of treatment with sodium lactate (NaLac) on the changes in brain energy state induced by a severe diffuse TBI. Rats were assigned to one of the eight groups (n = 10 per group): 1—sham, normal saline; 2—TBI, normal saline; 3—TBI, hypertonic saline; 4—TBI, 100 mM NaLac, 5—TBI, 500 mM NaLac; 6—TBI, 1280 mM NaLac; 7—TBI, 2000 mM NaLac and 8-TBI-500 mM NaLac + magnesium sulfate. Cerebrums were removed 6 h after trauma. Metabolites representative of the energy state (ATP, ATP-catabolites), N-acetylaspartate (NAA), antioxidant defenses (ascorbic acid, glutathione), markers of oxidative stress (malondialdehyde, ADP-ribose) and nicotinic coenzymes (NAD +) were measured by HPLC. TBI induced a marked decrease in the cerebral levels of ATP, NAA, ascorbic acid, glutathione and NAD + and a significant rise in the content of ATP-catabolites, malondialdehyde and ADP-ribose. These alterations were not ameliorated with NaLac infusion. We observed a significant reduction in cerebral NAD +, an essential co-enzyme for mitochondrial lactate-dehydrogenase that converts lactate into pyruvate and thus replenishes the tricarboxylic acid cycle. These results suggest that the metabolic pathway necessary to consume lactate may be compromised following a severe diffuse TBI in rats.

Hypothesis: Using the Warburg effect against cancer by reducing glucose and providing lactate

The avid consumption of glucose with concomitant lactate production by malignant cells, even under aerobic conditions, is called the Warburg effect, or aerobic glycolysis. This metabolic state is a final common pathway that apparently serves various invasive purposes. As most invasive tumours display the Warburg effect, this has proven of great clinical importance in detecting malignancies with 18-fluorine 2-deoxyglucose positron emission tomography (FDG-PET) scans. However, using the Warburg effect to target malignancies has proven more difficult. Since hypoglycaemia has been shown to be tumouricidal for cancers that display the Warburg effect, various schemes to block glucose utilization have been investigated. But in vivo it is difficult to selectively target glucose utilization in malignant cells without harming normal cells. Cancer cells produce large amounts of lactate under the Warburg effect, without fully oxidizing it to CO(2). In contrast normal cells can completely oxidize lactate under aerobic conditions. Recent studies have demonstrated that vital organs such as the brain, heart, liver, kidneys and muscle are capable of oxidizing lactate as a fuel alternative to glucose. It has also been shown that during hypoglycaemia intravenous lactate can serve as a salvage fuel in man. Other clinical studies showed that patients can effectively metabolize large amounts of exogenous lactate. All this appears to reflect the recently recognized major physiological role of lactate as a glucose alternative. Consequently, lactate is the most logical candidate to serve as a salvage fuel when local or systemic hypoglycemia is induced. Thus, we hypothesize that the combination of hypoglycaemia induced by insulin and concomitant lactate administration will selectively suppress cancers manifesting the Warburg effect, since such cancers will have great difficulty in metabolizing lactate. This metabolic therapy could be modulated in many ways both in amplitude, in duration and in timing with respect to other therapies. The validated isolated limb perfusion (ILP) model for sarcoma appears an attractive model to evaluate local therapy with insulin and lactate and test its (adjuvant) tumouricidal effects in animals and man. Such effects could be evaluated with modern metabolic detection techniques such as FDG-PET and magnetic resonance imaging in local models both in animals and humans. Subsequently the systemic effects of hypoglycaemia combined with sodium lactate administration could be evaluated.

Fructose-1,6-Bisphosphate Has Anticonvulsant Activity in Models of Acute Seizures in Adult Rats

A variety of observations suggest that decreasing glycolysis and increasing levels of reduced glutathione, generated by metabolism of glucose through the pentose phosphate pathway, would have an anticonvulsant effect. Because fructose-1,6-bisphosphate (F1,6BP) shifts the metabolism of glucose from glycolysis to the pentose phosphate pathway, it was hypothesized to have anticonvulsant activity. The anticonvulsant activity of F1,6BP was determined in rat models of acute seizures induced by pilocarpine, kainic acid, or pentylenetetrazole. The efficacy of F1,6BP was compared with that of 2-deoxyglucose (2-DG; an inhibitor of glucose uptake and glycolysis), valproic acid (VPA), and the ketogenic diet. One hour before each convulsant, Sprague Dawley rats received either saline (as seizure controls), F1,6BP (0.25, 0.5 or 1 g/kg), 2-DG (0.25 or 0.5 g/kg), or VPA (0.3 g/kg). Additional animals received the ketogenic diet (starting at 20 or 60 d old). Time to seizure onset, seizure duration, and seizure score were measured in each group. F1,6BP had dose-dependent anticonvulsant activity in all three models, whereas VPA had partial efficacy. 2-DG was only effective in the pilocarpine model. The ketogenic diet had no effect in these models. F1,6BP was also partially effective when given at the first behavioral seizure after pilocarpine. Administration of sodium lactate, which bypasses the block in the glycolytic pathway, abolished the anticonvulsant activity of 2-DG in the pilocarpine model, but only decreased the efficacy of F1,6BP. These data demonstrate that F1,6BP has significant anticonvulsant efficacy.

Respiratory Responses to Intravenous Infusion of Sodium Lactate in Male and Female Wistar Rats

In patients with panic disorder or premenstrual dysphoria, anxiety attacks can be triggered by intravenous administration of sodium lactate. Since respiratory symptoms, such as hyperventilation and shortness of breath, are characteristic features of spontaneous as well as lactate-induced panic, an involvement of central or peripheral chemoreceptors in this reaction has been suggested. In the present study, we examined to what extent intravenous infusion of sodium lactate influences respiratory parameters in freely moving male and female Wistar rats. Prompted by clinical reports suggesting that the susceptibility to spontaneous and lactate-induced anxiety may be influenced by the menstrual cycle, we also investigated if the effect of lactate on respiration in female rats is estrus cycle-dependent. Male and ovariectomized female rats exposed to sodium lactate displayed a larger increase in respiratory rate than rats given an infusion of saline. In intact female rats, the response to lactate infusion was significantly more pronounced in the diestrus phase than in the proestrus/estrus phase of the cycle. It is concluded that sodium lactate is a respiratory stimulant in rat, and that this effect is influenced by female sex steroids.

Increased response to a putative panicogenic nocebo administration in female patients with panic disorder

Experimental challenge studies may generate and test hypotheses regarding the pathophysiology of panic disorder and may serve to identify pathophysiologically relevant subtypes. It has been suggested that gender-related differences may be relevant in the development and maintenance of panic disorder. In a randomized double blind design the effects of placebo and sodium lactate administration in 14 female and 16 male patients with panic disorder and 23 healthy control subjects were compared using the Acute Panic Inventory (API) score and derived formal criteria for a panic attack. Panic attack frequency following sodium lactate was 76.6% in the patient group. Although control subjects had a lacate-induced increase in the API score as well, this effect was much weaker. No panic attacks occurred in patients with panic disorder or healthy control subjects receiving a placebo. However, a gender effect was observed in the putative panicogenic placebo condition: female patients with panic disorder had more subthreshold panic anxiety as measured with the API score. The data give evidence for an increased nocebo response in female patients with panic disorder.

Sodium Lactate Elicits a Rapid Increase in Blood Pressure in Wistar Rats and Spontaneously Hypertensive Rats

Intravenous administration of sodium lactate in concentrations (0.5 M, 2 M) previously shown to elicit panic attacks in patients with panic disorder was found to cause a prompt and short-lasting increase in blood pressure in spontaneously hypertensive (SH) rats and in normotensive Wistar rats; in contrast, only weak and nonsignificant effects of lactate were observed in rats of the Sprague-Dawley strain. The effects of lactate on heart rate in SH rats varied; thus, whereas most rats displayed a modest bradycardia during lactate infusions, in some rats the increase in blood pressure was accompanied by an increase in heart rate. After pretreatment with antipanic medication [the serotonin and noradrenaline reuptake inhibitor clomipramine (10 mg/kg/day, 3 weeks) or the triazolobenzodiazepine alprazolam (2 mg/kg/day, 3 weeks)], the blood pressure response to sodium lactate in SH rats was significantly blunted; in contrast, acute pretreatment with clomipramine (10 mg/kg) did not reduce the response. It is suggested that further studies on the cardiovascular effects of sodium lactate in SH or Wistar rats may shed further light on the mechanisms underlying the panic-provoking effect of lactate in panic disorder patients and on the mode of action of antipanic drugs.

Sodium lactate elicits a rapid increase in blood pressure in Wistar rats and spontaneously hypertensive rats: Effect of pretreatment with the antipanic drugs clomipramine and alprazolam

Intravenous administration of sodium lactate in concentrations (0.5 M, 2 M) previously shown to elicit panic attacks in patients with panic disorder was found to cause a prompt and short-lasting increase in blood pressure in spontaneously hypertensive (SH) rats and in normotensive Wistar rats; in contrast, only weak and nonsignificant effects of lactate were observed in rats of the Sprague-Dawley strain. The effects of lactate on heart rate in SH rats varied; thus, whereas most rats displayed a modest bradycardia during lactate infusions, in some rats the increase in blood pressure was accompanied by an increase in heart rate. After pretreatment with antipanic medication [the serotonin and noradrenaline reuptake inhibitor clomipramine (10 mg/kg/day, 3 weeks) or the triazolobenzodiazepine alprazolam (2 mg/kg/day, 3 weeks)], the blood pressure response to sodium lactate in SH rats was significantly blunted; in contrast, acute pretreatment with clomipramine (10 mg/kg) did not reduce the response. It is suggested that further studies on the cardiovascular effects of sodium lactate in SH or Wistar rats may shed further light on the mechanisms underlying the panic-provoking effect of lactate in panic disorder patients and on the mode of action of antipanic drugs.

Effect of Lactate on the Absorption and Retention of Aluminum in the Remnant Kidney Rat Model

In previous investigations we found the gastrointestinal absorption of aluminum (Al) to be enhanced in uremic rats and this phenomenon could not be attributed to either calcitriol deficiency or secondary hyperparathyroidism. The purpose of this study was to examine whether carboxyl ligands such as lactate could affect the absorption of A1 in our model and, if so, whether this would impose additional alterations on the A1 absorption in uremia. Uremic rats and controls were studied with single oral loads of either A1 chloride or A1 lactate and, subsequently, urinary A1 excretion was measured for 5 days. Compared with Al chloride, administration of A1 lactate resulted in significantly higher urinary excretion rates of A1 in uremic rats (55.5 +/- 22.7 vs. 27.4 +/- 7.0 micrograms; 2.06 +/- 0.84 vs. 1.01 +/- 0.26 mumol) and in controls (23.6 +/- 8.5 vs. 11.9 +/- 4.3 micrograms; 0.87 +/- 0.31 vs. 0.44 +/- 0.16 mumol). However, with either A1 load the recovery of A1 from urine was substantially higher in uremic animals. In contrast, only in controls was there a more pronounced rise in serum A1 concentrations following ingestion of A1 lactate, whereas in uremic rats this increase had a similar magnitude following A1 chloride and A1 lactate, suggesting a larger apparent volume of distribution of the latter. Adjustment of the pH of the A1 lactate-containing solution to 7.0 or oral administration of sodium lactate together with A1 chloride yielded essentially similar results. These observations indicate that the enhanced intestinal absorption of A1 in uremia is further augmented by lactate regardless of the mixture of hydroxolactato complexes employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactate and hyperventilation substantially attenuate vagal tone in normal volunteers. A possible mechanism of panic provocation?

Many aspects of panic attacks, eg, palpitations, tremor, sweating, and an emotional sense of "fear," have been theorized to arise from sympathetic nervous system activation. However, most studies have not demonstrated clearly increased levels of catecholamines during an attack, which is contrary to this hypothesis. To explore another possible cause for the physiological changes known to occur during a panic attack, we assessed parasympathetic nervous system activity by measuring vagal tone during treatments known to produce panic symptoms: sodium lactate administration and hyperventilation. Our findings showed a marked reduction in vagal tone during both procedures. We postulate that withdrawal of parasympathetic activity may explain some of the physiological changes occurring in panic attacks and be contributing to the origin of panic.

A nonhuman primate model of panic disorder

In this article we report on the reliable production of several features of panic attacks following subcutaneous administration of sodium lactate to nonhuman primates. Unrestrained monkeys were evaluated by an observer without knowledge of the subjects' treatment with either sodium lactate or a dextrose control solution. The lactate produced temporally circumscribed episodes of agitation, wariness, and motor responses, normally elicited under stressful or threatening conditions. In an initial pharmacological intervention, we found that pretreatment with imipramine blocked the response to lactate. The further development of this model offers promise for the systematic examination of etiological factors in susceptibility to lactate induction of panic attacks, the physiological basis of the response, and new modes of treatment of panic disorder.

Hepatic and extrahepatic lactate metabolism in sheep: effects of lactate loading and pH.

Hepatic lactate metabolism was studied in five sheep receiving infusions of either lactic acid or sodium lactate using an arteriovenous difference technique. Hepatic uptake of lactate was a saturable process with second order (Michaelis-Menten) kinetics. Although lactic acid infusion decreased blood pH, hepatic saturation of lactate uptake occurred before changes in pH could influence hepatic lactate metabolism. The Vmax for hepatic lactate metabolism is 5.72 mmol X kg-0.75 X h-1 and the Km 3.06 mmol/l. These findings have therapeutic relevance. In acidosis, the hepatic response to therapeutic administration of sodium lactate during fluid therapy will be variable. If plasma lactate is low, lactated fluids may increase hepatic uptake and produce an alkalizing effect. If plasma lactate is already high, hepatic lactate metabolism is nearly saturated, and additional lactate will not produce a hepatic alkalizing response. Extrahepatic tissues switch from lactate production to lactate utilization under conditions of lactate loading. They remove more lactate than liver at high plasma lactate concentrations. Muscle may be important in lactate removal in certain types of exercise.

Intravenous sodium lactate administration in respiratory alkalosis secondary to severe brain injuries

In acute cerebrovascular accidents the uptake of lactate by the brain tissue is enhanced, possibly in an attempt to buffer the increased local lactic acidosis. In this paper the results obtained by the administration of the lactate in 78 cases of hyperventilatory syndromes secondary to acute brain injuries, and the biochemistry of the cerebrospinal fluid and blood, are reported.

Renal excretion of uric acid during prolonged fasting

Serum and urine uric acid were evaluated during prolonged therapeutic fasting in 15 obese patients. With increasing ketonemia the serum uric acid rose from a control value of 5.9 ± 0.4 to 12.5 ± 1.0 mg 100 ml at 7 days and then decreased progressively to 7.7 ± 1.3 mg 100 ml by 28 days despite sustained ketonemia. The uric acid clearances were 5.5 ± 0.9, 1.8 ± 0.2, and 4.4 ± 1.5 ml/min at days 0, 7, and 28 of fasting. At the same times the creatinine clearances were 114 ± 11, 80 ± 6, and 64 ± 6.3 ml/min. There was no evidence of a renal tubular abnormality as assessed by glycosuria, bicarbonaturia, or increased phosphaturia. Urate binding to plasma proteins remained unchanged. Acute studies of the renal handling of uric acid revealed a uricosuric response to the administration of sodium lactate or sodium bicarbonate by intravenous infusion and low-dose acetylsalicylic acid orally. This renal tubular response departs significantly from that observed during the overnight fasted state and could not be accounted for by extracellular fluid volume expansion or the induced acid-base changes.

Role of acetate in the reduction of plasma free fatty acids produced by ethanol in man

To investigate the mechanism by which ethanol lowers plasma free fatty acids, we tested the ability of two products of alcohol metabolism, acetate and lactate, to lower free fatty acids in man. Sodium acetate was given orally to five healthy fasting volunteers and caused a significant fall in plasma free fatty acids. After amounts of ethanol and acetate that produced similar reductions in free fatty acids, plasma acetate increased 3- to 4-fold within 20 min. In each of three subjects the fall of free fatty acids observed after acetate ingestion occurred at plasma acetate levels less than or equal to those reached after ethanol. In all studies plasma glucose remained stable. Oral administration of sodium lactate to another volunteer in amounts sufficient to raise plasma lactate concentrations to a level similar to that found after ethanol administration failed to lower plasma free fatty acids. Thus acetate, a metabolite of ethanol, reduces plasma free fatty acids at plasma acetate levels comparable to those resulting from ethanol metabolism, which suggests that the lowering of plasma free fatty acids produced by ethanol is mediated, at least in part, by acetate.