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Mathematical modeling was used to explore the interaction between glucose, insulin, and lactate during the frequently sampled intravenous glucose tolerance test (FSIGTT). Insulin-modified FSIGTs were performed in 25 lean volunteers, and an additional 5 volunteers underwent FSIGTs with glucose injection alone to illustrate the effect of insulin on both glucose and lactate kinetics. The model chosen as the best representation of the system extended the minimal model of glucose kinetics (MM) by including a two-compartment model of lactate kinetics. The model accounted for both glucose and lactate kinetics, provided traditional MM parameters of insulin sensitivity and glucose effectiveness, and descriptive parameters of lactate kinetics. Modeling suggested that lactate production was limited by the rate of glucose disappearance, with no indication of direct effects of insulin on lactate. Inclusion of lactate kinetics had no adverse effect on MM parameters (SG: 0.023 ± 0.009 vs. 0.023 ± 0.010 min−1,SI: 1.01 ± 0.70 vs. 1.03 ± 0.71 × 104 · min−1 · pmol−1 · 1; P < 0.50, lactate model vs. MM), and indicated that ∼1.2% min−1 of total glucose disappearance during the FSIGT is converted to lactate. An additional benefit of including lactate kinetics was the significant improvement in precision in MM parameter estimates as reflected by the fractional standard deviations (FSDs). This effect was most prominent for SG, in which a threefold improvement in parameter precision was observed (FSD: 13.5 ± 3.1 vs. 42.5 ± 48.5; means ± SD). These analyses indicate that kinetic information for both glucose and lactate can be derived from FSIGT data and provide insights into the interaction between glucose, insulin, and lactate under non-steady-state conditions.

The shuttling of intermediary metabolites such as lactate through the vasculature contributes to the dynamic energy and biosynthetic needs of tissues. Tracer kinetic studies offer a powerful tool to measure the metabolism of substrates like lactate that are simultaneously taken up from and released into the circulation by organs, but in each circulatory passage, the entire cardiac output traverses the pulmonary parenchyma. To determine whether transpulmonary lactate shuttling affects whole-body lactate kinetics in vivo, we examined the effects of a lactate load (via lactate clamp, LC) and epinephrine (Epi) stimulation on transpulmonary lactate kinetics in an anesthetized rat model using a primed-continuous infusion of [U-13C]lactate. Under all conditions studied, control 1.2 (SD 0.7) (Con), LC 1.9 (SD 2.5), and Epi 1.9 (SD 3.5) mg/min net transpulmonary lactate uptake occurred. Compared with Con, a lactate load via LC significantly increased mixed central venous ([v̄]) [1.9 mM (SD 0.5) vs. 4.7 (SD 0.4)] and arterial ([a]) [1.6 mM (SD 0.4) vs. 4.1 (SD 0.6)] lactate concentrations ( P < 0.05). Transpulmonary lactate gradient ([v̄] − [a]) was highest during the lactate clamp condition [0.6 mM (SD 0.7)] and lowest during Epi [0.2 mM (SD 0.5)] stimulation ( P < 0.05). Tracer measured lactate fractional extractions were similar for control, 16.6% (SD 15.3), and lactate clamp, 8.2% (SD 15.3) conditions, but negative during Epi stimulation, −25.3% (SD 45.5) when there occurred a transpulmonary production, the conversion of mixed central venous pyruvate to arterial lactate. Further, isotopic equilibration between L and P occurred following tracer lactate infusion, but depending on compartment (v̄ or a) and physiological stimulus, [L]/[P] concentration and isotopic enrichment ratios ranged widely. We conclude that pulmonary arterial-vein concentration difference measurements across the lungs provide an incomplete, and perhaps misleading picture of parenchymal lactate metabolism, especially during epinephrine stimulation.

1. 1. In this short review, previous studies regarding the modeling of lactate (La) response to exercise and its application to endurance training have been summarized. 2. 2. Additionally the result of a recent study by the present authors are shown. 3. 3. Several models for La response to step and ramp exercise are already proposed and deductions derived from them are used for practical purposes such as the prediction of race performance in middle-and long-distance runners as well as for construction of their training regimens. 4. 4. Only a limited number of models however have tried to quantify whole body La kinetics to exercise in humans concomitantly with describing physiological mechanisms underlying the observed phenomenon. 5. 5. In a recent study described further in this paper a 2 compartment model was used for the purpose of clarifying the current “La production vs degradation” controversy during La adaptation to training. 6. 6. It was determined from this investigation that the La metabolic clearance rate during recovery is enhanced by the endurance training. 7. 7. This is in accordance with another recent observation of an increased La metabolic clearance rate at high absolute work rates and all relative work rates during exercise.

Summary The methodology developed for studying lactate movements during recovery depends on the following four basic assumptions: i) the endogenous natural lactate accumulated in the organism at the end of exercise can be used as its own tracer; ii) blood lactate curves supply information on the lactate distribution and displacements in the body; iii) the information on lactate movements and distribution becomes available through an appropriate mathematical analysis of blood lactate time courses; iv) lactate movements in the body can be studied from arterial blood which has a similar lactate concentration as that of mixed venous blood. A unique mathematical descriptive model including two exponential terms to describe the rapid and the slow components can be used to represent blood lactate recovery curves from muscular exercise. A two-compartmental model consisting of the previously worked muscles and the remainder of the lactate space furnishes the simplest but nevertheless the most realistic explanation of the lactate evolution pattern. The velocity constants of the first (γ1) and the second (γ2) exponential functions inform respectively on the abilities of the body to exchange and remove lactate during recovery. Different physiological factors, among them, work rate, exercise duration, and training status can modify the numerical values of the model parameters, thus demonstrating its capability to account for the expected events or modifications occurring at the tissular or cellular levels during these situations.

Summary Lactate kinetics in whole blood of horses was investigated after exercise of differing velocities and duration. The following categories of exercise were used: A: 180 seconds (n=35), B: >11 m/second and

The lactate turnover rate of rainbow trout (Oncorhynchus mykiss) was measured by bolus injection of [U-14C]lactate at rest and during prolonged swimming at 85% Ucrit to determine the importance of this metabolic fuel for endurance locomotion in fish, to assess whether lactate exchange between white and red muscle could be a possible mechanism for supplying oxidizable fuel to their lateral red muscle, and to compare the contribution of lactate to total energy provision between teleost and mammalian species. Turnover rate only increased from 4.41±0.33 to 9.71±1.69 μmolkg−1min−1 between rest and prolonged swimming, and the contribution of lactate oxidation to total metabolism declined during exercise. Lactate exchange between white and red muscle is, therefore, not a significant mechanism to fuel the active lateral red musculature during prolonged swimming. The lactate turnover rate of teleosts is one or two orders of magnitude lower than in mammals of equivalent size, but lactate has the same importance as a fuel in both vertebrate groups. However, lactate turnover rate and oxidation rate do not scale with body mass in the same fashion as does metabolic rate. The slope of the mammalian relationship for whole-body lactate turnover and oxidation is much lower (0.58) than the slope of the classic relationship for metabolic rate (0.75), indicating that lactate is a much more important oxidative substrate for small than for large animals.

Of the two types of lactic acidosis, Type B is the most difficult to explain in terms of mechanisms of lactic acid accumulation because the tissue hypoxia that accompanies Type A is not present except as a terminal event. The methods of pharmacokinetics show that for lactate to accumulate to an extent that would disturb acid-base balance, either lactate synthesis or lactate removal would have to be increased or decreased, respectively, by about 7-10-fold. To produce lactic acidosis within a few hours, synthesis would have to increase at the same time as clearance decreased. At normal contribution of the liver to the total lactate clearance (30%-40%), a total cessation of hepatic lactate clearance would not result in lactic acidosis without a concomitant rise in the rate of lactate synthesis. Again, to produce an acidosis this increase would have to be about 8-fold at a normal fractional hepatic clearance. The control of hepatic lactate uptake is discussed in the light of the relatively low hepatic extraction of lactate and in relation to to two main models of hepatic drug (lactate) clearance; the 'well-stirred' and 'parallel-tube' models.

A tracer washout method was employed to study the kinetics of lactate disappearance from the blood in exercised and unexercised channel catfish. Following 5 min of strenuous exercise, the plasma lactate rose from 0.34 to 6.57μ mol mL⁻¹, but glucose did not increase significantly. The peak lactate concentration in the plasma was reached 10 min after exercise and fell to control values by 4 h after exercise. As the plasma lactate declined following infusion, there was a pulse of radioactivity in glucose, indicating significant gluconeogenesis. The rate constant for lactate clearance was not significantly elevated after exercise, indicating little change in the dynamics of lactate metabolism. Catfish appear to handle the lactate load from anaerobic exercise much faster than other species of fish and do not appear to retain significant amounts of lactate in muscle.

The recent modeling technique to lactate (La) kinetics in exercise, and its availability, application, and limitation were summarized. Two examples were come up for discussion. One is the application of the compartment model (i.e., the description by the linear differential equations) to systemic La kinetics in exercise, and the other is the current controversy on anaerobic threshold, that is, the reexamination of the several proposed models of blood La kinetics during ramp exercise. In conclusion, considering the various limitations in current in vivo experimental approach on man, the theoretical approach with mathematical modeling, as one of the major strategies, gives full play to clarify the La metabolism in exercise.

We review the contribution of mathematical modeling of metabolic pathways to the study of the compartmentalization of brain energy metabolism between neurons and glia. We especially focus on the role of lactate in the relationship between glia and neurons and the possible presence of an astrocyte-neuron lactate shuttle (ANLS). We first discuss models of glucose, pyruvate, and lactate kinetics, which are relevant to neuron-glia interactions. We then review models of compartmentalized energy metabolism, which deal with the concepts of 'red' and 'white' stimulations, and the ANLS hypothesis. We next show the contribution of a study of model robustness to the debate about the potential role of lactate in metabolic interactions between glia and neurons. Finally, we discuss the possible implications of modeling for further experimental studies.

Competitive inline speedskating combines a movement pattern similar to speedskating on ice with pack-oriented competition modes known from cycling. The deep-seated body position leads to high static load and, thus, restricted blood flow within propulsive muscles. This condition may affect lactate kinetics and limit V.O (2peak). The present study compares physiologic reactions to graded cycling and skating exercise among top-level inline speedskaters and quantifies the effect of drafting. Eight male inline speedskaters of the top national level were examined. The study consisted of two graded exhaustive exercise tests (cycling and speedskating) and a pairwise drafting test. All tests were carried out with simultaneous gas exchange (MetaMax 2, Cortex, Germany) and heart rate measurements as well as determination of blood lactate concentrations. Maximal values of oxygen consumption (cycling: 4.91 +/- 0.60; skating: 4.85 +/- 0.50 l . min (-1); p = 0.78), lactate concentration, or heart rate were similar for cycling and skating. At workloads corresponding to blood lactate concentrations of 4 mmol . l (-1) oxygen uptake (cycling: 3.24 +/- 0.65; skating: 3.97 +/- 0.40 l . min (-1); p < 0.05) and heart rate (cycling: 162 +/- 9; skating: 173 +/- 6 min (-1); p < 0.05) were significantly higher during skating. The differences in heart rate ranged between - 2 and 23 min (-1). The drafting effect was 15 +/- 6 % at 30 km . h (-1) (3.34 +/- 0.19 vs. 2.83 +/- 0.29 l . min (-1)) and 14 +/- 5 % at 33 km . h (-1) (3.87 +/- 0.26 vs. 3.32 +/- 0.27 l . min (-1)). During inline speedskating the attainment of VO2peak is not impaired when compared to cycling exercise. However, the derivation of exercise prescriptions from a stepwise cycling test does not seem appropriate. The drafting effect of inline speedskating is within the range known from cycling.

The in vivo assessment of lactate distribution and metabolism is difficult since lactate is released and disposed in all the tissues of the body. This makes the traditional noncompartmental approach to estimate parameters of lactate kinetics very limited and dependent on the site of infusion/sampling mode. We propose here a new compartmental model of lactate kinetics which accounts for the two arterial-venous and venous-arterial infusion/sampling modes in a circulatory physiology context and allows the estimation of masses and fluxes in non-accessible pools, e. g. the intracellular release of lactate. Aspects related to optimal experiment design for model identification are discussed.

Understanding cerebral energy metabolism in neurons and astrocytes is necessary for the interpretation of functional brain imaging data. It has been suggested that astrocytes can provide lactate as an energy fuel to neurons, a process referred to as astrocyte—neuron lactate shuttle (ANLS). Some authors challenged this hypothesis, defending the classical view that glucose is the major energy substrate of neurons, at rest as well as in response to a stimulation. To test the ANLS hypothesis from a theoretical point of view, we developed a mathematical model of compartmentalized energy metabolism between neurons and astrocytes, adopting hypotheses highly unfavorable to ANLS. Simulation results can be divided between two groups, depending on the relative neuron versus astrocyte stimulation. If this ratio is low, ANLS is observed during all the stimulus and poststimulus periods (continuous ANLS), but a high ratio induces ANLS only at the beginning of the stimulus and during the poststimulus period (triphasic behavior). Finally, our results show that current experimental data on lactate kinetics are compatible with the ANLS hypothesis, and that it is essential to assess the neuronal and astrocytic NADH/NAD+ ratio changes to test the ANLS hypothesis.

The present study investigated whether muscular monocarboxylate transporter (MCT) 1 and 4 contents are related to the blood lactate removal after supramaximal exercise, fatigue indexes measured during different supramaximal exercises, and muscle oxidative parameters in 15 humans with different training status. Lactate recovery curves were obtained after a 1-min all-out exercise. A biexponential time function was then used to determine the velocity constant of the slow phase (γ2), which denoted the blood lactate removal ability. Fatigue indexes were calculated during 1-min all-out (FIAO) and repeated 10-s (FISprint) cycling sprints. Biopsies were taken from the vastus lateralis muscle. MCT1 and MCT4 contents were quantified by Western blots, and maximal muscle oxidative capacity ( Vmax) was evaluated with pyruvate + malate and glutamate + malate as substrates. The results showed that the blood lactate removal ability (i.e., γ2) after a 1-min all-out test was significantly related to MCT1 content ( r = 0.70, P < 0.01) but not to MCT4 ( r = 0.50, P > 0.05). However, greater MCT1 and MCT4 contents were negatively related with a reduction of blood lactate concentration at the end of 1-min all-out exercise ( r = −0.56, and r = −0.61, P < 0.05, respectively). Among skeletal muscle oxidative indexes, we only found a relationship between MCT1 and glutamate + malate Vmax ( r = 0.63, P < 0.05). Furthermore, MCT1 content, but not MCT4, was inversely related to FIAO ( r = −0.54, P < 0.05) and FISprint ( r = −0.58, P < 0.05). We concluded that skeletal muscle MCT1 expression was associated with the velocity constant of net blood lactate removal after a 1-min all-out test and with the fatigue indexes. It is proposed that MCT1 expression may be important for blood lactate removal after supramaximal exercise based on the existence of lactate shuttles and, in turn, in favor of a better tolerance to muscle fatigue.

Venous-arterial lactate differences across the brain during lactate infusion in rats were studied, and the fate of lactate was described with a mathematical model that includes both cerebral and extracerebral kinetics. Ultrafiltration was used to sample continuously and simultaneously arterial and venous blood. Subsequent application of flow injection analysis and biosensors allowed the measurement of glucose and lactate concentrations every minute. Because of the high temporal resolution, arteriovenous lactate kinetics could be modeled in individual experiments. The existence of both a cerebral lactate sink and a lactate exchangeable compartment, representing approximately 24% of brain volume, was thus modeled.

The present study investigated whether blood lactate removal after supramaximal exercise and fatigue indexes measured during continuous and intermittent supramaximal exercises are related to the maximal muscle oxidative capacity in humans with different training status. Lactate recovery curves were obtained after a 1-min all-out exercise. A biexponential time function was then used to determine the velocity constant of the slow phase (γ2), which denoted the blood lactate removal ability. Fatigue indexes were calculated during all-out (FIAO) and repeated 10-s cycling sprints (FISprint). Biopsies were taken from the vastus lateralis muscle, and maximal ADP-stimulated mitochondrial respiration ( Vmax) was evaluated in an oxygraph cell on saponin-permeabilized muscle fibers with pyruvate + malate and glutamate + malate as substrates. Significant relationships were found between γ2 and pyruvate + malate Vmax ( r = 0.60, P < 0.05), γ2 and glutamate + malate Vmax ( r = 0.66, P < 0.01), and γ2 and citrate synthase activity ( r = 0.76, P < 0.01). In addition, γ2, glutamate + malate Vmax, and pyruvate + malate Vmax were related to FIAO (γ2 − FIAO: r = 0.85; P < 0.01; glutamate + malate Vmax − FIAO: r = 0.70, P < 0.01; and pyruvate + malate Vmax − FIAO: r = 0.63, P < 0.01) and FISprint (γ2 − FISprint: r = 0.74, P < 0.01; glutamate + malate Vmax − FISprint: r = 0.64, P < 0.01; and pyruvate + malate Vmax − FISprint: r = 0.46, P < 0.01). In conclusion, these results suggested that the maximal muscle oxidative capacity was related to blood lactate removal ability after a 1-min all-out test. Moreover, maximal muscle oxidative capacity and blood lactate removal ability were associated with the delay in the fatigue observed during continuous and intermittent supramaximal exercises in well-trained subjects.

We determined the effect of 20 nights of live high, train low (LHTL) hypoxic exposure on lactate kinetics, monocarboxylate lactate transporter proteins (MCT1 and MCT4), and muscle in vitro buffering capacity (βm) in 29 well-trained cyclists and triathletes. Subjects were divided into one of three groups: 20 consecutive nights of hypoxic exposure (LHTLc), 20 nights of intermittent hypoxic exposure [four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia (LHTLi)], or control (Con). Rates of lactate appearance (Ra), disappearance (Rd), and oxidation (Rox) were determined from a primed, continuous infusion of l-[U-14C]lactic acid tracer during 90 min of steady-state exercise [60 min at 65% peak O2 uptake (V̇o2 peak) followed by 30 min at 85% V̇o2 peak]. A resting muscle biopsy was taken before and after 20 nights of LHTL for the determination of βm and MCT1 and MCT4 protein abundance. Ra during the first 60 min of exercise was not different between groups. During the last 25 min of exercise at 85% V̇o2 peak, Ra was higher compared with exercise at 65% of V̇o2 peak and was decreased in LHTLc ( P < 0.05) compared with the other groups. Rd followed a similar pattern to Ra. Although Rox was significantly increased during exercise at 85% compared with 65% of V̇o2 peak, there were no differences between the three groups or across trials. There was no effect of hypoxic exposure on βm or MCT1 and MCT4 protein abundance. We conclude that 20 consecutive nights of hypoxia exposure decreased whole body Ra during intense exercise in well-trained athletes. However, muscle markers of lactate metabolism and pH regulation were unchanged by the LHTL intervention.

The maximal lactate steady state (MLSS) is the highest blood lactate concentration (BLC) that can be identified as maintaining a steady-state during a prolonged submaximal constant workload. Comparative interpretation of published data about MLSS is complicated by the fact that different methods of testing have been utilized. Thus, three methods, corresponding to the time course of changes in BLC incurred during either 30 min (MLSS I) or 20 min (MLSS II and III) of constant submaximal workload exercise, were compared in 26 male subjects [mean (SD) age 24.6 (5.6) years, height 181.6 (4.9) cm, body mass 74.4 (5.2) kg]. MLSS I [5.1 (1.3) mmol x l(-1)], II [4.9 (1.3) mmol x l(-1)], and III [4.3 (1.3) mmol x l(-1)] were different (P0.01). The workload corresponding to MLSS III [244.8 (44.0) W] was lower (P0.01) than that at MLSS I [254.0 (40.8) W] and II [251.9 (40.4) W]. No difference could be confirmed between the workloads established for MLSS I and MLSS II. The differences between MLSS I, MLSS II, and MLSS III and corresponding workloads reflect insufficient contribution to lactate kinetics by testing procedures that depend strongly upon the time course of changes in BLC during the initial 20-25 min of constant-workload exercise. Based on the present findings, constant-load tests lasting at least 30 min and a BLC increase of no more than 1.0 mmol x l(-1) after the 10th testing minute appear to be the most reasonable with respect to valid testing results.

We sought to compare the association of whole blood lactate kinetics with survival in patients with septic shock undergoing early quantitative resuscitation.

We investigated NaHCO3 infusion effects on plasma lactate removal by forearm muscles and performance during intensive leg exercise. Seven subjects performed the force-velocity (FV) test with placebo and NaHCO3 (2 mEq.min-1) with a double-blind crossover protocol. Blood samples for arterial ([LA]A) and venous ([LA]V) lactate determinations were taken 1) at rest before infusion, and 2, 6, 10, 14, 18, and 22 min following its start; and 2) at the end of each exercise bout. The arteriovenous difference ([LA]A-V) was determined for each sampling. NaHCO3 significantly increased arterial bicarbonate concentration and pH during rest (P0.001; P0.001) and the FV test (P0.001; P0.05). During the test, [LA]A and [LA]V were significantly higher with NaHCO3 (P0.05, P0.001). At test onset, [LA]A-V became positive and increased until the braking force of 6 kg, with NaHCO3 and placebo, with values significantly lower for NaHCO3 (P0.001). Peak anaerobic power (Wanae, peak) and the corresponding braking force (Fmax) were also determined. Fmax was significantly increased with NaHCO3 (P0.001). In conclusion, the increasing rise in [LA]A and [LA]V induced by NaHCO3 may be partly explained by a decreased rate of lactate uptake by forearm skeletal muscles. NaHCO3 did not improve Wanae, peak, but improved Fmax, thus increasing FV duration.

To study how two types of testing protocols for the determination of the [LA] and blood pH kinetics during running match each other, a group of nine runners participated in two testing protocols. The first protocol consisted of a sequences of 8 x 2000 m runs at constant speed, which was increased on different testing days. The first protocol was used for the determination of running speed (v), [LA], pH and heart rate (HR) corresponding to the Lactate Threshold (LT) and the Threshold of Acidosis (TA), both occurring at similar running speeds (4.21 +/- 0.44 and 4.22 +/- 0.40 m/s) (mean +/- SD) and HR (159 +/- 7 and 160 +/- 9 1/min), [LA] = 2.0 +/- 0.6 mmol/l and pH = 7.411 +/- 0.018. Maximal steady values for [LA] (maxLAss) and minimal steady values for pH (minpHss) obtained by the second protocol were higher (p < 0.01) according to running speed (4.62 +/- 0.38 and 4.66 +/- 0.38 m/s), HR (172 +/- 7 and 174 +/- 8 1/min) and [LA] (5.7 +/- 1.3 mmol/l) and lower according to pH (7.364 +/- 0.021), respectively. Unlike similar running speeds determined by LT and TA, the minimal steady pH level occurred at a slightly higher speed than the speed at maxLAss. Additionally, we found a drift of pH towards a resting level, when [LA] fluctuated around a steady level. Furthermore, the parameters of pH kinetics correlated better with the running speed of the 4000 m run that was taken as the parameter of short endurance performance, than those of [LA] kinetics. We conclude that these differences in [LA] and pH kinetics could serve to predict the capabilities of runners with respect to the two endurance performance types: long and short.

We are pleased to respond to the comment by Loranne Agius (1) relating to our recent article in Diabetes Care (2). Overall, we are in agreement with Agius that further well-designed studies are needed to validate the underlying assumptions of the model. For that purpose, we are already performing studies that will help clarify these questions. Nevertheless, a point was raised in Agius’s letter that we wanted to comment on further. As stated by Agius, one possible explanation for the 50% difference in our estimates of glucokinase activity and that of Iozzo et al. (3) may be …

The relationship between blood lactate concentration (LA) and oxygen uptake (VO 2 ) during incremental exercise remains controversial: Does LA increase continuously as a function of VO 2 or does it begin to increase above a particular threshold? These competing models are investigated here. In this work, a time series model of LA-VO 2 kinetics, with work rate as input and VO 2 and LA as outputs, was fitted to published data. The time course of the estimated model parameters suggests an alternative to the continuous and threshold models. Two major transitions were found to occur at intensity levels equivalent to 53 ± 8 % VO 2 max and 77 ± 9 % VO 2 max. Thus, the metabolic rate domain is divided into three main regions, each with distinct dynamics.

To study the effects of age and training on lactate production in older trained subjects, the lactate kinetics of highly trained cyclists [HT, n = 7; 65 (SEM 1.2) years] and control subjects with low training (LT, n = 7) and of similar age were compared to those of young athletes [YA, n = 7; 26 (SEM 0.7) years], during an incremental exercise test to maximum power. The results showed that the lactacidaemia at maximal oxygen uptake (VO2max) was lower for HT than for LT (P < 0.05) and, in both cases, lower than that of YA (P < 0.001). The respective values were HT: 3.9 (SEM 0.51), LT: 5.36 (SEM 1.12), and YA: 10.3 (SEM 0.63) mmol.l-1. At submaximal powers, however, the difference in lactacidaemia was not significant between HT and YA, although the values for lactacidaemia at VO2max calculated per watt and per watt normalized by body mass were significantly lower for HT (P < 0.001) and LT (P < 0.02). These results would indicate that the decline in power with age induced a decline in lactacidaemia. Yet this loss in power was not the only causative factor; indeed, our results indicated a complementary metabolic influence. In the older subjects training decreased significantly the lactacidaemia for the same submaximal power (P < 0.01) and from 60% of VO2max onwards (P < 0.05); as for YA it postponed the increase and accumulation of lactates. The lactate increase threshold (Thla-,1) was found at 46% VO2max for LT and at 56% VO2max for HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients after myocardial infarction have different lactate kinetics compared to healthy subjects (4, 5). The aim of this study was to examine the relationship between left ventricular function and the lactate kinetics during and after exercise in a large number of patients.

It has been known for long that trained subjects (TR) can exercise at higher relative work loads (WLmax) compared to untrained subjects (UT) in endurance exercise. This higher endurance capacity in TR (1, 6) is assumed to be the consequence of an increase in anaerobic metbolism only at higher percentage of WLmax compared to UT. Therefore, the endurance capacity is often “measured” by the relationship between blood lactate concentration [Lac] and work load (WL) (7, 11, 17, 21, 27, 28). The prerequisites are that [Lac] should be lower at the same %WLmax and that the increase should begin at higher relative work loads (WLrel) in TR compared to UT. Such a relationship has been found by several authors (9, 13, 16).

Arterial blood lactate concentrations were determined in two groups of eleven males before, during and after near 2 W.kg body mass-1 bicycle exercise. One group of subjects cycled for 3 min, whereas the second group exercised for 60 min. All the lactate curves during recovery could be fitted to a bi-exponential time function consisting of a rapidly increasing and a slowly decreasing component. This typical evolution pattern indicates that the two-compartment model which has been proposed to represent the movements of lactate after short exercise applies also to recovery from prolonged exercise. Lengthening exercise duration decreased (respectively 10% and 28%) the value of both velocity constants of the fits to the lactate recovery curves, with the difference (28%) being statistically significant for the velocity constant describing the slowly decreasing part of the curves. This result indicates that extending exercise from 3 to 60 min impairs the ability to remove lactate after the exercise.

Seventeen healthy male volunteers participated in this study designed to compare arterial with both arterialized venous and venous lactate kinetics after short exercise. Blood samples drawn before, during, and after bicycle exercise were analyzed continuously for lactate. A mathematical function incorporating two exponential terms was fitted to the arterial, arterialized venous, and venous lactate recovery curves, and the parameters of the mathematical function were compared using a linear regression. All parameters measured on or fitted to the arterialized venous curves correlated well with the respective arterial data (correlation coefficient R = 0.82 to 0.99, P less than 0.001). Among the parameters obtained from the fit to the venous curves, only those describing lactate removal correlated closely with the arterial results. It is concluded that for lactate kinetic studies during recovery following short-term muscular exercise, the information obtained from arterialized venous blood is comparable to arterial blood, whereas the use of venous blood, from the sampling site in this study, appears suitable for determining only the parameters for lactate disappearance. These conclusions are illustrated by the comparison between arterial, arterialized venous, and venous parameters as a function of the work rate of the previously performed exercise.

The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U-14C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production.

Glucose and lactate kinetics were examined in fed and food-deprived American eels, Anguilla rostrata (LeSueur), under MS 222 anaesthesia (AE). These values are compared to free-swimming, non-anaesthetized animals (FSE) reported previously (Cornish & Moon, 1985). The AE group demonstrated a steady but minor hyperglycemia during the 5-h experiment and significant decreases in both glucose turnover and metabolic clearance rates compared to the FSE groups. Food-deprivation further depressed these kinetic parameters. Blood lactate continuously increased during the experiment, reaching values 300 times (fed) and 100 times (food-deprived) higher than the similar FSE groups. Consistent with these higher concentrations, rates of lactate appearance in and disappearance from the blood generally increased with anaesthesia. This study supports the view of Soivio et at. (1977) that MS 222 acts as an asphyxiant. The associated metabolic disruptions are consistent with a reduction in oxidative in favour of anaerobic tissue metabolism. The specific changes in glucose and lactate parameters reflect the nervous and hormonal disruptions occurring with anaesthesia. These studies urge caution in the interpretation of data using an anaesthetized fish preparation.

To investigate the relationships between oxygen consumption (VO2) and the rates of systemic lactate appearance (Ra) and disappearance (Rd), six healthy males were studied at rest and during continuous graded exercise using a primed continuous infusion of lactate tracer. Subjects exercised for 6 min at 300, 600, 900, and 1,200 kg . m . min-1. L-(+)-[1-14C]lactate was infused intravenously, and arterial samples were drawn at rest and every 2 min throughout the exercise period. Ra and Rd were calculated using nonsteady-state equations. At rest Ra and Rd were 14.4 +/- 1.8 and 15.1 +/- 2.2 mumol . kg-1 . min-1, respectively. Near steady-state values were observed toward the end of the first two work loads. Ra and Rd values were 32.8 +/- 2.3 and 37.4 +/- 1.3 mumol . kg-1 . min-1 during min 5 and 6 at 300 kg . m . min-1 and were 59.1 +/- 2.6 and 55.4 +/- 2.3 mumol . kg-1 . min-1 during min 5 and 6 at 600 kg . m . min-1. Ra was significantly greater than Rd at both 900 and 1,200 kg . m . min-1. Ra and Rd averaged 145.4 +/- 10.5 and 110.2 +/- 5.6 mumol . kg-1 . min-1, respectively, during the last 2 min at 900 kg . m . min-1, and 309.4 +/- 20.8 and 169.7 +/- 10.6 mumol . kg-1 . min-1, respectively, at 1,200 kg . m . min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise with stepwise increasing work loads until exhaustion leads to a curvilinear increase of lactate in blood and typical lactate kinetics in the post-exercise period. Lactate kinetics in blood during exercise and recovery results from diffusion along gradients between muscle and blood and simultaneous elimination. Therefore, a general diffusion-elimination model is presented from which maximal rate of elimination (Em), individual anaerobic threshold (IAT), gradient between muscle and blood (deltaC-deltaCEm), muscle volume working above the IAT (Vm), individual membrane constant (Mc), quantity of lactate accounting for lactate gradient (Agrad), and whole body lactate (Anet) can be obtained. For demonstration purpose, this model was applied to a highly trained athlete. In this example, all constants and variables mentioned above as well as an equation reflecting individual lactate kinetics were calculated. Furthermore, the IAT was determined in 61 athletes participating in different events. In general, it can be demonstrated that with increasing aerobic capacity the lactate concentration at the IAT decreases. The lactate concentration at the IAT varies interindividually within broad limits, thus emphasizing the need for individual assessment.

Glucose turnover was measured in rats subjected to experimental peritonitis. Fifteen hours following cecal ligation and puncture or sham surgery, rats were anesthetized with pentobarbital and glucose metabolism was estimated by constant infusion tracer techniques. Septic rats demonstrated significantly elevated rates of glucose appearance without any elevation of plasma glucose concentration. There was also significant hyperlactacidemia in the cecally ligated rats. The elevated plasma lactate was not accompanied by a lowering of blood pH. Arterial blood pressures were not different between groups, however the blood pressure of septic rats did fall during the infusion experiment. Septic rats demonstrated significantly elevated initial heart rates and blood hematocrit. The turnover of lactate was also elevated in the septic rats. By calculation of the relative percentage of glucose production from labeled lactate, it is obvious that septic rats had elevated rates of gluconeogenesis. Determination of plasma immunoreactive insulin indicated that septic rats were not insulin resistant.

Simultaneous infusion of [6-3H]glucose and [U-14C]lactate was used to calculate the turnover rate of glucose, the irreversible replacement rate of lactate, and the rates of the exchange of carbon atoms between glucose and lactate in free-swimming American eels (Anguilla rostrata) fed or food deprived for 6, 15, and 36 (maturing) mo. The mean turnover rate of glucose in fed animals averaged 1.0 mg X min-1 X 100 g-1, while the lactate irreversible replacement rate was approximately 4.0 micrograms X min-1 X 100 g-1. The conversion of 35% of lactate carbon to glucose implied a substantial Cori cycle activity, but this amounted to less than 1% of total glucose production. Food deprivation for 6 mo altered few kinetic patterns, except for an increased lactate irreversible replacement rate and a minor increase in gluconeogenesis from lactate. After a 15-mo fast, glucose turnover decreased to 0.09 +/- 0.02 mg X min-1 X 100 g-1. Plasma lactate concentrations and production rates continuously increased during the experiment. Maturing eels that had been food deprived for 36 mo maintained glucose and lactate concentrations and kinetics similar to values in animals food deprived for only 6 mo. This study stresses the importance of carbohydrate in the metabolism of this species under fed and food-deprived conditions and further supports the tolerance of Anguillid species to food deprivation.

Plasma lactate turnover rate of Thoroughbred racehorses was measured by bolus injection of [U-14C]lactate at rest and two levels of submaximal treadmill exercise (3-4 m/s trot, 6% incline, and 6.5 m/s horizontal canter). Our goals were 1) to determine the relative effects of changes in cardiac output and in plasma lactate concentration on turnover rate [using cardiac output data from Weber et al. (28)] and 2) to assess the importance of lactate as a metabolic fuel in a trained animal athlete. Lactate turnover rates were 9.3 mumol.min-1.kg-1 (rest), 75.9 mumol.min-1.kg-1 at the beginning of the trot protocol [45% maximum O2 uptake (VO2max)], 50.3 mumol.min-1.kg-1 later in the same protocol (50% VO2max), and 66.1 mumol.min-1.kg-1 during the canter protocol (55% VO2max). Both changes in cardiac output and in plasma lactate concentration had a significant effect on turnover rate. Variation in plasma lactate fluxes of Thoroughbreds during exercise follows the standard mammalian pattern, but this substrate only plays a minor role as an oxidizable fuel in horses. The oxidation of plasma lactate accounts for less than 5% of metabolic rate (VO2) during submaximal work. Adjustments in cardiac output and in metabolite concentration represent, respectively, the coarse and fine controls for the regulation of plasma metabolite turnover rate.

The development of any model requires testing of both the underlying assumptions and the final values calculated from the model. In this paper we present examples of the interaction between empirical testing and the development of models designed to help in the investigation of glucose, lactate, and pyruvate kinetics in vivo. Experimental evidence is presented which demonstrates that a model of glucose kinetics should account for the two physical pools in which glucose is distributed — plasma and interstitial fluid. When such a model is used to determine rapid changes in the rate of appearance of unlabeled glucose with measurements made from both compartments, accuracy is improved markedly in certain non-steady state situations over the traditional Steele equation. In the case of lactate kinetics, it is demonstrated that when the proper isotope infusion/sampling mode is used, impossible values for lactate production are obtained using the traditional approach for calculation. However, in demonstration of the failure of that model, new information was obtained which led to the development of a new model to quantify pyruvate kinetics.

Prolonged physical exercise tests (50 min) at the threshold of 4 mmol . l-1 lactate (ATc) and at the individual anaerobic threshold (IAT) were applied in 19 rowing athletes. In each of the rowers (n = 19) work loads corresponding to the IAT did not result in a gradual lactase accumulation or exhaustion within 50 min of exercise. Means of lactate concentration and heart rate at the end of exercise were 4.0 +/- 1.6 mmol . l-1 and 182 +/- 13.0 beats . min-1, respectively. In 15 of 19 rowers, the IAT corresponded to lower work loads than the ATc. In these cases, prolonged exercise tests at the ATc showed gradual increases in lactate concentrations to a mean of 9.6 +/- 1.2 mmol . l-1, associated with exhaustion at a mean working time of 14.4 +/- 6.3 min and a mean heart rate of 192 +/- 10.4 beats . min-1. In four rowers, the IAT was found at identical (n = 3) or higher (n = 1) work loads than the ATc. In these cases, after an initial increase no further rise in lactate concentrations in blood was observed, and exhaustion did not occur during the prolonged exercise tests. These findings support the conclusion derived from the lactate kinetics model that the IAT defines the work load at the maximal lactate steady state.

Arterial blood lactate was measured at 10 s time intervals after a 3 min strenuous exercise for six athletes pedaling a bicycle ergometer in the sitting position. Recovery curves were fitted to the equation: Y(t) = A1(1-e-gamma1t)+A2(1-e-gamma2t)(0). The evolution of arterial lactate concentrations during recovery can accurately be represented by this equation. The values of the coefficients A and gamma found were used for a numerical application to an open two-compartment model: the "working muscle space" (1) and the "lactate space" (2). Intramuscular concentrations, the transfer coefficients from compartment 1 to compartment 2 and from compartment 2 to compartment 1 and the fractional turnover and basal turnover rate were calculated. Computed intramuscular lactate concentrations at the end of exercise compare favorably with those found earlier by muscular biopsic samplings. The turnover data are higher than those previously reported. This discrepancy may possibly be attributed to the method of mathematical analysis.