Dialysate Lactate Concentrations Research Articles

Optimizing serum total carbon dioxide concentration during short and nocturnal frequent hemodialysis using lactate as dialysate buffer base.

Definitive clinical studies to determine the optimal dialysate lactate concentration to prescribe during frequent hemodialysis when using the NxStage System One dialysis delivery system at low dialysate flow rates have not been reported. We used clinical data from patients who transferred from in-center thrice-weekly hemodialysis (ICHD) to daily home hemodialysis using the NxStage System One and the H+ mobilization model to calculate acid generation rates in patient sub-groups during the FREEDOM study. Assuming those acid generation rates were representative, we then predicted using the H+ mobilization model the effect of using dialysate lactate concentrations of 40 and 45 mEq/L on predialysis serum total carbon dioxide (tCO2 ) concentrations in patients who transfer from ICHD to short and nocturnal frequent hemodialysis prescriptions used in current clinical practice; the prescriptions evaluated varied by treatment frequency, dialysate volume per treatment, and treatment times. With frequencies of four to six treatments per week and treatment times of 170 to 210 minutes per treatment, the effect of dialysate lactate concentration was primarily dependent on weekly dialysate volume. For weekly dialysate volumes of 150 to 160 L per week, use of dialysate lactate concentrations of 45 mEq/L, but not 40 mEq/L, resulted in an increase of predialysis serum tCO2 concentration. When longer treatment times typical of nocturnal frequent hemodialysis were evaluated, model predictions showed that the use of dialysate lactate concentration of 45 mEq/L may not be appropriate for many patients because of excessive increases in predialysis serum tCO2 concentration. Reducing dialysate volume from 60 to 30 L may limit the increase in predialysis serum tCO2 concentration when patients transfer from ICHD to nocturnal frequent hemodialysis. Predictions from the H+ mobilization model show that dialysate lactate concentration and weekly dialysate volume are the primary prescription parameters for optimizing predialysis serum tCO2 concentration during short and nocturnal frequent hemodialysis.

Effect of dialysate potassium and lactate on serum potassium and bicarbonate concentrations during daily hemodialysis at low dialysate flow rates

BackgroundObservational studies of hemodialysis patients treated thrice weekly have shown that serum and dialysate potassium and bicarbonate concentrations are associated with patient outcomes. The effect of more frequent hemodialysis on serum potassium and bicarbonate concentrations has rarely been studied, especially for treatments at low dialysate flow rate.MethodsThese post-hoc analyses evaluated data from patients who transferred from in-center hemodialysis (HD) to daily HD at low dialysate flow rates during the FREEDOM Study. The primary outcomes were the change in predialysis serum potassium and bicarbonate concentrations after transfer from in-center HD (mean during the last 3 months) to daily HD (mean during the first 3 months).ResultsAfter transfer from in-center HD to daily HD (data from 345 patients, 51 ± 15 years of age, mean ± standard deviation), predialysis serum potassium decreased (P < 0.001) by approximately 0.4 mEq/L when dialysate potassium concentration during daily HD was 1 mEq/L; no change occurred when dialysate potassium concentration during daily HD was 2 mEq/L. After transfer from in-center HD to daily HD (data from 284 patients, 51 ± 15 years of age), predialysis serum bicarbonate concentration decreased (P = 0.0022) by 1.0 ± 3.3 mEq/L when dialysate lactate concentration was 40 mEq/L but increased (P < 0.001) by 2.5 ± 3.5 mEq/L when dialysate lactate concentration was 45 mEq/L. These relationships were dependent on serum potassium and bicarbonate concentrations during in-center HD.ConclusionsControl of serum potassium and bicarbonate concentrations during daily HD at low dialysate flow rates is readily achievable; the choice of dialysate potassium and lactate concentration can be informed when transfer is from in-center HD to daily HD.

Skeletal muscle lactate overproduction during metformin intoxication: An animal study with reverse microdialysis.

Lactic acidosis during metformin intoxication is classically mainly attributed to diminished lactate clearance through liver gluconeogenesis. Here we studied 6 healthy, sedated and mechanically ventilated pigs to clarify whether high dose of metformin also increases skeletal muscle lactate production. Each animal had two microdialysis catheters inserted in gluteus muscles, one per side. One catheter was infused with saline (control) while the other one was infused with metformin diluted in saline (1M), both at a rate of 0.3μl/min. Dialysate lactate concentration and lactate-to-pyruvate ratio, a marker of the balance between anaerobic glycolysis and aerobic (mitochondrial) metabolism, were measured every 3h, for 12h. Continuous infusion of metformin caused a progressive rise in dialysate lactate level (p=0.007) and lactate-to-pyruvate ratio (p<0.001) compared to that of saline, as for mitochondrial "poisoning". These findings suggest that skeletal muscle lactate overproduction contributes to the development of metformin-induced lactic acidosis.

Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients

Abstract Context: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extra-pancreatic mechanisms. Objective: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism. Design: Randomized, double blind, crossover study. Setting: Academic clinical research center. Patients: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m2. Intervention: Seven days treatment with the selective DPP-4 inhibitor vildagliptin or placebo. Standardized test meal on day seven. Main Outcome Measures: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin; dialysate glucose, lactate, pyruvate, glycerol. Results: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptine increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. Conclusions: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients

Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity, resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extrapancreatic mechanisms. We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism. We conducted a randomized, double-blind, crossover study at an academic clinical research center. Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m(2), participated. INTERVENTION included 7 d treatment with the selective DPP-4 inhibitor vildagliptin or placebo and a standardized test meal on d 7. Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin, dialysate glucose, lactate, pyruvate, glycerol were measured. Fasting and postprandial venous insulin, glucose, glycerol, triglycerides, and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptin increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

The Effect of Oral Glucose Loads on Tissue Metabolism During Angiotensin II Receptor and Beta-receptor Blockade in Obese Hypertensive Subjects

AT1 receptor blockers and ACE inhibitors decrease the risk for new onset diabetes mellitus. The phenomenon could be related to a direct angiotensin II effect on tissue metabolism. To address the issue, we recruited eighteen obese hypertensive patients. Patients were randomized to double-blind treatment with either valsartan (n = 8) or atenolol (n = 10) for thirteen weeks. They underwent an oral glucose tolerance test before and during active treatment, while metabolism was monitored through subcutaneous and intramuscular microdialysis and indirect calorimetry. After glucose ingestion, venous glucose and insulin concentrations increased rapidly while systemic free fatty acid concentrations were suppressed. Dialysate glucose and lactate concentrations increased briskly in adipose tissue and in skeletal muscle. Dialysate glycerol decreased profoundly in both tissues. Respiratory quotient increased markedly after glucose ingestion. These responses were identical at baseline and during active treatment either drug. We conclude that AT1 receptor blockade in obese hypertensive patients has no effect on interstitial glucose supply, lipolysis, and substrate oxidation. One possible explanation is that angiotensin II levels in obese hypertensives are not sufficient to elicit the metabolic changes that have been observed after direct angiotensin II application. The exact mechanism by which inhibition of the renin-angiotensin-aldosterone system decreases the diabetes risk remains unresolved and requires further study.

Hypoxia is not the sole cause of lactate production during shock.

Traditionally, elevated blood lactate after hemorrhage is interpreted as tissue hypoperfusion, hypoxia, and anaerobic glycolysis. The severity and duration of the increase in blood lactate correlate with death. Recent in vitro studies indicate that epinephrine stimulates lactate production in well-oxygenated skeletal muscle by increasing activity of the Na+-K+-adenosine triphosphatase (ATPase), which derives a significant amount of adenosine triphosphate from glycolysis. Using in vivo microdialysis, we tested whether inhibiting the Na+-K+ pump with ouabain could reduce muscle lactate production during local exposure, via the microdialysis probe, to epinephrine or during hemorrhage in rats. Microdialysis catheters were placed in the muscle of both thighs of pentobarbital-anesthetized male Sprague-Dawley rats (275-350 g) and perfused (1 microL/min) with Krebs-phosphate buffer (pH 7.4) containing ethanol (5 mmol/L) to permit assessment of changes in local blood flow. To inhibit the Na+-K+-ATPase, ouabain (2-3 mmol/L) was added to the perfusate of one leg. In one series of studies, epinephrine was added to the perfusate. In another series, rats were hemorrhaged to a mean arterial pressure of 45 mm Hg for 30 minutes, followed by resuscitation with shed blood and 0.9% sodium chloride. Dialysate fractions were analyzed for lactate and ethanol fluorometrically. Lactate rose during epinephrine exposure or during hemorrhage and resuscitation. Treatment with ouabain reduced dialysate lactate concentration significantly in both series of studies. Local blood flow was reduced by either epinephrine or hemorrhage, but returned toward baseline afterward. Ouabain had no apparent effect on local blood flow. Increased Na+-K+ATPase activity during epinephrine treatment or hemorrhage contributes to muscle lactate production. Hypoxia is not necessarily the sole cause of hyperlactatemia during and after hemorrhagic shock.

Regional changes in cerebral extracellular glucose and lactate concentrations following severe cortical impact injury and secondary ischemia in rats.

Traumatic brain injury (TBI) causes the brain to be more susceptible to secondary insults, and the occurrence of a secondary insult after trauma increases the damage that develops in the brain. To study the synergistic effect of trauma and ischemia on brain energy metabolites, regional changes in the extracellular concentrations of glucose and lactate following a severe cortical impact injury were measured employing a microdialysis technique. Three microdialysis probes were placed in center of the impact site, in an area adjacent to the impact site, and in the contralateral parietal cortex, and perfused with artificial cerebrospinal fluid (CSF) at 2 microl/min. Rats were assigned to one of the following experimental groups (n = 7 per group): (1) combined impact injury and secondary insult, (2) impact injury with sham secondary insult, (3) sham impact with secondary insult, or (4) sham impact and sham secondary insult. The impact injury was produced with a pneumatic impactor (5 m/sec, 3-mm deformation). One hour following the impact injury, a secondary insult was produced by bilateral carotid occlusion for 1 h. The impact injury resulted in a three- to fivefold global increase in dialysate lactate concentrations, with a corresponding fall in dialysate glucose concentration by 50% compared to no change in lactate or glucose concentrations in sham-injured animals (p < .0001 for both lactate and glucose). The secondary insult resulted in a second increase in dialysate lactate and decrease in dialysate glucose concentration that was significantly greater in the animals that had suffered the impact injury than in the sham-injured animals. Ischemia and traumatic injury have synergistic effects on lactate accumulation and on glucose depletion in the brain that probably reflects persisting ischemia, but may also indicate mitochondrial abnormalities and inhibition of oxidative metabolism.

Effects of hyperinsulinemia and hyperglycemia on lactate release and local blood flow in subcutaneous adipose tissue of healthy humans.

To determine the effects of hyperglycemia and hyperinsulinemia on lactate production by adipocytes, healthy volunteers were studied during three experimental protocols. In protocol 1, the changes in interstitial lactate concentrations were measured by microdialysis (sc tissue) after oral glucose administration. The plasma lactate concentration increased by 39.4 +/- 6.0%, and the dialysate lactate concentration increased by 117.9 +/- 16.3%. In protocol 2, a 2.5-h hyperinsulinemic euglycemic clamp and somatostatin infusion were performed. The plasma and dialysate lactate concentrations increased by 27.1 +/- 5.5% and 146.8 +/- 44.5%, respectively. In addition, [U-13C]glucose was infused through the probe, and dialysate lactate was enriched in 13C at 2.5 +/- 0.3 molar percent excess basally and at 3.4 +/- 0.3 molar percent excess during the clamp (P < 0.05 vs. basal). [13C]Urea was also infused through the probe, and the outflow to inflow ratio of [13C]urea was used as an index of local blood flow. It decreased by 10.2 +/- 3.6% (P < 0.001) at the end of the hyperinsulinemic euglycemic clamp, indicating an increase in blood flow. In protocol 3, a hyperglycemic clamp (10.0 mmol/L) at the basal insulin concentration was performed. It increased the dialysate lactate concentration by 43.5 +/- 15.9% and did not alter the plasma lactate concentration or local blood flow. It is concluded that hyperinsulinemia and, to a lesser extent, hyperglycemia stimulate glucose conversion into lactate in adipocytes. Hyperinsulinemia, but not hyperglycemia, also increases adipose tissue blood flow.

Myocardial interstitial purine metabolites and lactate with increased work in swine

Dobutamine stimulates the beta-receptors in the heart and increases myocardial blood flow and oxygen consumption 2-3-fold, similar to effects seen with exercise. The purpose of this study was to assess temporal changes in myocardial interstitial purine metabolites, adenosine monophosphate (AMP) and lactate during and following 30 min of dobutamine infusion. Dobutamine (15 micrograms/kg/min) was infused via the jugular vein into 9 anesthetized, open-chest, domestic swine. Interstitial fluid was sampled with microdialysis probes placed in the midmyocardium. The effluent from the probes, referred to as the dialysate, was used to estimate myocardial interstitial purine metabolites, AMP, and lactate levels before, during, and following a dobutamine-induced increased work state. Dobutamine infusion resulted in a 77% increase in heart rate, a 258% increase in left ventricular dP/dt, a 208% increase in myocardial oxygen consumption, and a 155% increase in rate x pressure product. Myocardial blood flow was increased in the subepicardium, midmyocardium, and subendocardium by 207, 268, and 268%, respectively, compared to the control period. Neither coronary venous nor dialysate lactate concentrations changed throughout the protocol. Dialysate adenosine and AMP levels were both significantly elevated (P < 0.05) during the dobutamine period and fell back to control values during the recovery period. The dobutamine-induced increases in myocardial oxygen consumption, rate x pressure product, and blood flow, without an increase in coronary venous or interstitial lactate suggest that energy balance is maintained during dobutamine infusion. Thus an increase in myocardial work, in the absence of demand-induced ischemia, resulted in accumulation of adenosine and AMP in the interstitium.

Effect of Daily Voluntary Running onIn VivoInsulin Action in Rat Skeletal Muscle and Adipose Tissue as Determined by the Microdialysis Technique

The effect of physical training on in vivo insulin-stimulated glucose utilization in relation to glycolysis (lactate formation) in rat peripheral tissues was investigated in 8 sedentary controls (SC) and 7 voluntary running rats (VR). We used a sequential euglycemic clamp procedure (insulin infusion rate; 6.0, 30.0 mU/kg.min) in combination with a microdialysis technique in M. quadriceps femoris, vastus lateralis, and inguinal adipose tissue. In the clamp study, glucose infusion rate (GIR) averaged over 45-75 min during the 6.0-mU/kg.min insulin infusion was significantly (p < 0.01) higher in VR (15.36 +/- 0.83 mg/kg.min, mean +/- SE) than in SC (10.41 +/- 0.88 mg/kg.min), and the lack of a significant difference in GIR between VR and SC was found during the 30.0-mU/kg.min insulin infusion. In these tissues, there was no significant difference in dialysate lactate levels between VR and SC in the basal state without insulin or glucose infusion, or at an insulin infusion rate of 30.0 mU/kg.min. However, dialysate lactate concentrations in muscle averaged over 45-75 min during the 6.0-mU/kg.min insulin clamp procedure in VR (8.51 +/- 0.71 mg/dl) were significantly (p < 0.05) higher than in SC (6.18 +/- 0.48 mg/dl). These results indicated that insulin action in skeletal muscle and adipose tissue could be evaluated in vivo by using the microdialysis technique, and that an increase in GIR in VR was, in part, explained by an increase in lactate formation in skeletal muscle.

Continuous monitoring of lactate during exercise in humans using subcutaneous and transcutaneous microdialysis.

We have evaluated the possibility of monitoring the plasma lactate concentration in human volunteers during cycle ergometer exercise using subcutaneous and transcutaneous microdialysis. In transcutaneous microdialysis, the relative increase in dialysate lactate concentration exceeded that of plasma lactate concentration by a factor of 6 during exercise due to exercise-induced lactate secretion in sweat. During exercise the subcutaneous microdialysis dialysate lactate concentration underestimated the plasma lactate concentration possibly due to diffusion limitation or adipose tissue lactate production. While it was demonstrated that microdialysis can be used for on-line lactate monitoring, neither subcutaneous nor transcutaneous dialysate lactate concentration were linearly related to the plasma lactate concentration during exercise, and it was found therefore that it was not possible to monitor directly plasma lactate concentration during exercise.

Interstitial glucose and lactate balance in human skeletal muscle and adipose tissue studied by microdialysis.

1. Microdialysis was used to gain insight into the substrate exchanges in the interstitial space of skeletal muscle and adipose tissue. Probes were inserted in the quadriceps femoris muscle and para-umbilical subcutaneous adipose tissue of thirteen subjects and microdialysis was performed at different flow rates (1-4 microliters min-1) and during changes in tissue blood flow. 2. When ethanol (5 mM) is included in the perfusion solution, the ethanol clearance from the probe is a measure of tissue blood flow. Blood flow changes induced by adenosine or vasopressin perfusion, by exercise or by circulatory occlusion resulted in ethanol clearance values of 69-139% of the basal level. The ethanol clearance was higher in skeletal muscle than in adipose tissue (32-62%, P < 0.001), a difference compatible with a higher blood flow in muscle tissue. 3. The fraction of the interstitial glucose concentration that was recovered with the microdialysis was similar in skeletal muscle (the absolute values being 1.70 +/- 0.14 mM at 1 microliter min-1 and 0.59 +/- 0.05 mM at 4 microliters min-1) and adipose tissue (1.89 +/- 0.20 mM at 1 microliter min-1; 0.54 +/- 0.05 mM at 4 microliters min-1) and correlated inversely with the tissue ethanol clearance, both in the basal state and during changes in tissue blood flow (muscle: r = -0.56 to -0.67; adipose tissue r = -0.72 to -0.95). Coefficients of variation were 6-8% (glucose) and 11-16% (lactate) and were similar during isometric exercise. The reproducibility of the technique (comparison of two contralateral probes; perfusion flow rate 4 microliters min-1) was 5.3-8.3% (ethanol) and 23.9-20.8% (glucose) in muscle (n = 6) and adipose tissue (n = 4) respectively. 4. The skeletal muscle dialysate lactate concentration (1 microliter min-1: 1.16 +/- 0.2 mM) was higher than in adipose tissue (0.76 +/- 0.08 mM, P < 0.05), where the absolute amount of lactate that could be removed from the tissue (at 4 microliters min-1) was only half of that in skeletal muscle (0.8 +/- 0.11 vs. 1.76 +/- 0.23 nmol min-1, P < 0.05). The dialysate lactate level was not affected in either tissue by large changes in the interstitial glucose concentration indicating that in neither tissue is blood glucose a significant source of lactate formation. 5. The blood flow effects on the dialysate glucose concentration are the likely consequence of probe glucose drainage artificially shifting the balance between the supply and consumption of interstitial glucose.(ABSTRACT TRUNCATED AT 400 WORDS)

The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis.

We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.