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Context Ghrelin circulates in acylated (AG) and deacylated (DAG) forms, which are known to affect appetite. Although acute exercise has been shown to modulate ghrelin levels, data on the impact of exercise intensity on AG and DAG levels and their effects on appetite are sparse and primarily limited to males. Objective To investigate the effect of exercise intensity and sex on ghrelin levels and appetite in untrained humans. Methods Eight males (age: 43.1 ± 10.9 years; body mass index [BMI]: 22.2 ± 1.7 kg/m2; peak oxygen consumption [VO2peak]: 36.3 ± 6.4 mL/kg/min) and 6 females (age: 32.2 ± 11.1 years; BMI: 22.7 ± 1.0 kg/m2; VO2peak: 29.2 ± 4.0 mL/kg/min) completed a maximal graded cycle ergometer lactate threshold (LT)/VO2peak test. These data were used to determine the exercise intensity on 3 subsequent randomized control or calorically matched cycle exercise bouts: (1) CON, no exercise; (2) MOD, the power output at LT; (3) HIGH, the power output associated with 75% of the difference between LT and VO2peak. Perception of appetite was analyzed using visual analog scales. Results Females had higher levels of total ghrelin (TG) (P =.03) and DAG (P =.01) at baseline than males. Both groups exhibited reduced DAG levels in HIGH compared with MOD and CON (P <.0001-.004); however, only females had significantly reduced AG in HIGH (P <.0001). Hunger scores were higher in MOD than in CON (P <.01). Conclusion High-intensity may be superior to moderate-intensity exercise for reducing ghrelin levels and modifying hunger, and sex may impact this response. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the present study were to investigate blood lactate kinetics following high intensity exercise and identify the physiological determinants of 800 m running performance. Methods: Fourteen competitive 800 m runners performed two running tests. First, participants performed a multistage graded exercise test to determine physiological indicators related to endurance performance. Second, participants performed four to six 30-s high intensity running bouts to determine post-exercise blood lactate kinetics. Using a biexponential time function, lactate exchange ability (γ1), lactate removal ability (γ2), and the quantity of lactate accumulated (QLaA) were calculated from individual blood lactate recovery data. Results: 800 m running performance was significantly correlated with peak oxygen consumption (r = −0.794), γ1 and γ2 at 800 m race pace (r = −0.604 and −0.845, respectively), and QLaA at maximal running speed (r = −0.657). V ˙ O2peak and γ2 at 800 m race pace explained 83% of the variance in 800 m running performance. Conclusion: Our results indicate that (1) a high capacity to exchange and remove lactate, (2) a high capacity for short-term lactate accumulation and, (3) peak oxygen consumption, are critical elements of 800 m running performance. Accordingly, while lactate has primarily been utilized as a performance indicator for long-distance running, post-exercise lactate kinetics may also prove valuable as a performance determinant in middle-distance running. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to ascertain the optimal test duration to elicit the highest maximal lactate formation rate ( V ˙ Lamax), whilst exploring the underpinning energetics, and identifying the optimal blood lactate sampling period. Methods: Fifteen trained to well-trained males (age 27 ± 6 years; peak power: 1134 ± 174 W) participated in a randomised cross-over design completing three all-out sprint cycling tests of differing test durations (10, 15, and 30 s). Peak and mean power output (W and W.kg−1), oxygen uptake, and blood lactate concentrations were measured. V ˙ Lamax and energetic contributions (phosphagen, glycolytic, and oxidative) were determined using these parameters. Results: The shortest test duration of 10 s elicited a significantly (p = 0.003; p < 0.001) higher V ˙ Lamax (0.86 ± 0.17 mmol.L−1.s−1; 95% CI 0.802–0.974) compared with both 15 s (0.68 ± 0.18 mmol.L−1.s−1; 95% CI 0.596–0.794) and 30 s (0.45 ± 0.07 mmol.L−1.s−1; 95% CI 0.410–0.487). Differences in V ˙ Lamax were associated with large effect sizes (d = 1.07, d = 3.15). We observed 81% of the PCr and 53% of the glycolytic work completed over the 30 s sprint duration was attained after 10 s. BLamaxpost were achieved at 5 ± 2 min (ttest 10 s), 6 ± 2 min (ttest 15 s), and 7 ± 2 min (ttest 30 s), respectively. Conclusion: Our findings demonstrated a 10 s test duration elicited the highest V ˙ Lamax. Furthermore, the 10 s test duration mitigated the influence of the oxidative metabolism during all-out cycling. The optimal sample time to determine peak blood lactate concentration following 10 s was 5 ± 2 min. [ABSTRACT FROM AUTHOR]

We prove the existence of an optimal treatment combining chemotherapy and a lactate targeting drug for a mathematical model for high grade gliomas and lactate kinetics. A necessary condition for a treatment to be optimal is also devised, allowing to design numerically the proper therapy. The analytical results are validated by the numerical simulations; as clinical experience proves, the simulations show that the effect of chemotherapy is enhanced by the other drug whose sole administration is, in turn, almost irrelevant. [ABSTRACT FROM AUTHOR]

This article discusses the concept of the Laffer curve, which was popularized by economist Arthur Laffer in the 1970s. The Laffer curve illustrates the relationship between tax rates and tax revenue, suggesting that there is an optimal tax rate that maximizes government revenue. The article then applies this concept to the study of lactate kinetics in physiology. Lactate is produced by cells during anaerobic metabolism and is used as a measure of tissue perfusion. The article suggests that there may be two states of perfusion that result in the same blood lactate concentration, which could have implications for the interpretation of lactate levels in clinical practice. [Extracted from the article]

We wanted to determine the influence of total blood volume (BV) and blood lactate quantity on lactate concentrations during incremental exercise. Twenty-six healthy, nonsmoking, heterogeneously trained females (27.5 ± 5.9 ys) performed an incremental cardiopulmonary exercise test on a cycle ergometer during which maximum oxygen uptake ( V · O2max), lactate concentrations ([La−]) and hemoglobin concentrations ([Hb]) were determined. Hemoglobin mass and blood volume (BV) were determined using an optimised carbon monoxide-rebreathing method. V · O2max and maximum power (Pmax) ranged between 32 and 62 mL·min−1·kg−1 and 2.3 and 5.5 W·kg−1, respectively. BV ranged between 81 and 121 mL·kg−1 of lean body mass and decreased by 280 ± 115 mL (5.7%, p = 0.001) until Pmax. At Pmax, the [La−] was significantly correlated to the systemic lactate quantity (La−, r = 0.84, p < 0.0001) but also significantly negatively correlated to the BV (r = −0.44, p < 0.05). We calculated that the exercise-induced BV shifts significantly reduced the lactate transport capacity by 10.8% (p < 0.0001). Our results demonstrate that both the total BV and La− have a major influence on the resulting [La−] during dynamic exercise. Moreover, the blood La− transport capacity might be significantly reduced by the shift in plasma volume. We conclude, that the total BV might be another relevant factor in the interpretation of [La−] during a cardio-pulmonary exercise test. [ABSTRACT FROM AUTHOR]

The aim of this paper is to first study a Cahn-Hilliard model for brain lactate kinetics with a control function. This control allows for optimal treatment administered to ill patients suffering from glioma, in order to reduce their brain lactate concentrations, and thereby to slow down the tumor growth. We establish the well-posedness of the problem and the continuity of the control-to-state mapping, the existence of a minimizer of the objective functional, and its Fréchet differentiability in suitable Banach spaces with respect to the control and with respect to time. Moreover, we derive the first-order necessary conditions that an optimal control has to satisfy. In the second part of the paper, we illustrate our theoretical results with numerical simulations using MRI data from the University Hospital of Poitiers. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate the relationship between blood lactate levels and lactate kinetics (lactate clearance and Δ lactate) for predicting mortality in patients with COVID-19 admitted to the emergency department. This study was performed as a retrospective study that included patients admitted to the emergency department between March 1st, 2020, and January 1st, 2022. Lactate levels were recorded at the first admission (0 h lactate) and the highest blood lactate levels in the first 24 h of follow-up (2nd highest lactate). Lactate kinetics were calculated. Clinical severity was determined according to the quick COVID Severity Index (qCSI). 300 patients were included in the study. Lactate levels at admission were similar in groups with or without mortality, but 2nd highest lactate levels were found to be significantly higher in the group with mortality (p < 0.001). Lactate clearance and ∆ lactate levels were also found to be lower in the mortality group (p < 0.001). Lactate kinetics in patients in the clinically low severity group were lower in the mortality group (p = 0.02 and p = 0.039, respectively). In the low-intermediate and high-intermediate groups, 0-h lactate and 2nd highest lactate levels were found to be higher in the mortality group, and lactate kinetics were similar in the groups with and without mortality. In the group with high clinical severity, 2nd highest lactate levels were found to be higher in the group with mortality (p = 0.010). Lactate kinetics were also found to be significantly lower in the mortality group (p < 0.001). In the high qCSI group, based on ROC analysis, the AUC for 2nd highest lactate levels predicting mortality was 0.642 (95% CI: 0.548–0.728). The optimal cut-off value for mortality was greater than >2.4 mmol/L (60.6% sensitivity, 67.4% specificity). The AUC for lactate clearance was 0.748 (95% CI: 0.659–0.824). The lactate clearance cut-off value was ≤ −177.78% (49.3% sensitivity, 100% specificity). The AUC for ∆ lactate was 0.707 (95% CI: 0.616–0.787). The optimal ∆ lactate cut-off was ≤ −2 mmol/L (45.1% sensitivity, 93.5% specificity). In COVID-19, 2nd highest blood lactate and lactate kinetics were found to be prognostic indicators of the disease. High 2nd highest lactate levels and low lactate kinetics in patients with high clinical severity were guiding physicians regarding the outcome of the disease. • Lactate has an important role in the follow-up of critically ill patients. • qCSI is an effective scoring system in the triage of critical Covid-19 patients in the emergency department. • Lactate clearance is effective in predicting mortality in critical Covid −19 patients [ABSTRACT FROM AUTHOR]

Introduction: Sepsis and septic shock cause significant mortality worldwide, with no targeted molecular therapies available. Metformin has pleomorphic effects that may be beneficial in sepsis, but at present, the impact of metformin exposure on sepsis remains controversial. Metformin might alter lactate metabolism, but little is known about its influence on lactate kinetics. We therefore investigated the impact of preadmission metformin use on lactate kinetics, acute kidney injury (AKI) and mortality in sepsis. Materials and Methods: We retrospectively analysed all ICU admissions with sepsis and septic shock between January 2013 and September 2020, identifying 77 users and 390 nonusers (subdivided in diabetics, n = 48 and nondiabetics, n = 342). Results: (Sub)groups did not differ in illness severity or sepsis aetiology. Admission lactate levels were similar, but evolution in lactate over the first 24 h showed a larger decrease in users vs nonusers (median − 53% vs. −36%, p =.010). No difference in AKI or renal replacement therapy was found. Mortality was lower in users vs nonusers in case of septic shock (21.9% (n = 7) vs. 42.7% (n = 61) for 90d mortality, p =.029, OR 0.38 [95% CI: 0.15–0.93]), but showed no significant differences in the combined sepsis and septic shock population. Conclusions: In our data, preadmission metformin use is associated with a significantly larger decrease in lactate after admission with sepsis or septic shock and with reduced mortality in septic shock. This underscores the need for further studies investigating the interplay between metformin, lactate and sepsis, thereby exploring the potential use of metformin or its pathways in sepsis. [ABSTRACT FROM AUTHOR]

Purpose: Enhanced external counterpulsation (EECP) is a recovery strategy whose use has increased in recent years owing to the benefits observed in the clinical setting in some cardiovascular diseases (ie, improvement of cardiovascular function). However, its claimed effectiveness for the enhancement of exercise recovery has not been analyzed in athletes. The aim of this study was to determine the effectiveness of EECP on short-term recovery after a fatiguing exercise bout. Methods: Twelve elite junior triathletes (16 [2] y) participated in this crossover counterbalanced study. After a high-intensity interval training session (6 bouts of 3-min duration at maximal intensity interspersed with 3-min rest periods), participants were assigned to recover during 30 min with EECP (80 mm Hg) or sham (0 mm Hg). Measures of recovery included performance (jump height and mean power during an 8-min time trial), metabolic (blood lactate concentration at several time points), autonomic (heart-rate variability at several time points), and subjective (rating of perceived exertion [RPE] and readiness to compete) outcomes. Results: There were no differences between EECP and sham in mean RPE or power output during the high-intensity interval training session, which elicited a significant performance impairment, vagal withdrawal, and increased blood lactate and RPE in both EECP and sham conditions (all P <.05). No significant differences were found in performance, metabolic, or subjective outcomes between conditions at any time point. A significantly lower high-frequency power (P <.05, effect size = 1.06), a marker of parasympathetic activity, was observed with EECP at the end of the recovery phase. Conclusion: EECP did not enhance short-term recovery after a high-intensity interval training session in healthy, highly trained individuals. [ABSTRACT FROM AUTHOR]

Abstract Introduction Sepsis and septic shock cause significant mortality worldwide, with no targeted molecular therapies available. Metformin has pleomorphic effects that may be beneficial in sepsis, but at present, the impact of metformin exposure on sepsis remains controversial. Metformin might alter lactate metabolism, but little is known about its influence on lactate kinetics. We therefore investigated the impact of preadmission metformin use on lactate kinetics, acute kidney injury (AKI) and mortality in sepsis. Materials and Methods We retrospectively analysed all ICU admissions with sepsis and septic shock between January 2013 and September 2020, identifying 77 users and 390 nonusers (subdivided in diabetics, n = 48 and nondiabetics, n = 342). Results (Sub)groups did not differ in illness severity or sepsis aetiology. Admission lactate levels were similar, but evolution in lactate over the first 24 h showed a larger decrease in users vs nonusers (median − 53% vs. −36%, p = .010). No difference in AKI or renal replacement therapy was found. Mortality was lower in users vs nonusers in case of septic shock (21.9% (n = 7) vs. 42.7% (n = 61) for 90d mortality, p = .029, OR 0.38 [95% CI: 0.15–0.93]), but showed no significant differences in the combined sepsis and septic shock population. Conclusions In our data, preadmission metformin use is associated with a significantly larger decrease in lactate after admission with sepsis or septic shock and with reduced mortality in septic shock. This underscores the need for further studies investigating the interplay between metformin, lactate and sepsis, thereby exploring the potential use of metformin or its pathways in sepsis.

The accumulation of lactate in muscle and blood during high-intensity exercise is negatively correlated with the duration exercise can be sustained. Removal of lactate is a key component of acute recovery between consecutive bouts of such exercise. Low-intensity exercise enhances recovery by accelerating lactate turnover in metabolically active tissues, largely mediated by blood flow to these tissues. Therefore, the purpose of this research was to clarify if L-citrulline, a nutritional supplement purported to promote vasodilation via enhanced nitric oxide availability, would augment the removal of blood lactate during active recovery (AR). L-citrulline ingestion will augment the rate of blood lactate concentration decrease during AR, reduce the oxygen-cost of submaximal exercise, and increase time-to-exhaustion and peak oxygen uptake (V̇O2peak) during a test of maximal aerobic power. Healthy university students (five males & five females) participated in this double-blind, randomized, placebo-controlled study. Participants exercised on a cycle ergometer at submaximal steady-state intensities followed by progressively increasing intensity to exhaustion, 10 min of AR, and then supramaximal intensity exercise to exhaustion. Oxygen uptake was measured throughout the trial and blood lactate was sampled repeatedly during AR. The protocol elicited very high peak blood lactate concentrations after exercise (11.3 + 1.3 mmol/L). L-citrulline supplementation did not significantly alter blood lactate kinetics during AR, the oxygen cost of exercise, V̇O2peak, or time-to-exhaustion. Despite a strong theoretical basis by which L-citrulline could augment lactate removal from the blood, L-citrulline supplementation showed no effect as an exercise-recovery supplement. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the optimal target e of lactate kinetics at different time during the resuscitation, the factors that influence whether the kinetics achieve the goals, and the clinical implications of different clinical phenotypes. Methods Patients with hyperlactatemia between May 1, 2013 and December 31, 2018 were retrospectively analyzed. Demographic data, basic organ function, hemodynamic parameters at ICU admission (T0) and at 6 h, 12 h, 24 h, 48 h, and 72 h, arterial blood lactate and blood glucose levels, cumulative clinical treatment conditions at different time points and final patient outcomes were collected. Results A total of 3298 patients were enrolled, and the mortality rate was 12.2%. The cutoff values of lactate kinetics for prognosis at 6 h, 12 h, 24 h, 48 h, and 72 h were 21%, 40%, 57%, 66%, and 72%. The APACHE II score, SOFA score, heart rate (HR), and blood glucose were risk factors that correlated with whether the lactate kinetics attained the target goal. Based on the pattens of the lactate kinetics, eight clinical phenotypes were proposed. The odds ratios of death for clinical phenotypes VIII, IV, and II were 4.39, 4.2, and 5.27-fold of those of clinical phenotype I, respectively. Conclusion Stepwise recovery of lactate kinetics is an important resuscitation target for patients with hyperlactatemia. The APACHE II score, SOFA score, HR, and blood glucose were independent risk factors that influenced achievement of lactate kinetic targets. The cinical phenotypes of stepwise lactate kinetics are closely related to the prognosis.

Introduction: Sepsis is one of the leading causes of death worldwide. Serum lactate is being used in sepsis for diagnostic and prognostic purposes for years now. In this study, we shed light over a novel use of lactate in form of various clearance parameters to determine mortality in septic patients at the 28th day. Materials and method: In our study, 200 patients with sepsis were included using quick sequential organ failure assessment (qSOFA) score and their lactate levels were measured at the time of admission (0 hour) and 24 hours after admission. Lactate clearance parameters (absolute and relative lactate clearance, lactate clearance rate) were calculated. All patients were followed up for a period of 28 days to determine the outcome, and data analysis was done accordingly. Results and conclusion: Our study showed that higher SOFA score, qSOFA score, and serum lactate levels were associated with increased 28th-day mortality. Low absolute, relative lactate clearance and lactate clearance rate were also associated with poor outcomes. The best cutoffs to predict poor outcomes were serum lactate level at 24 hours ≥4 mmol/L and relative lactate clearance ≤40.3% with good sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Abstract Background Venous–arterial carbon dioxide (CO2) to arterial–venous oxygen (O2) content difference ratio (Cv-aCO2/Ca-vO2) > 1 is supposed to be both sensitive and specific for anaerobic metabolism. What regional hemodynamic and metabolic parameters determine the ratio has not been clarified. Objectives To address determinants of systemic and renal, spleen, gut and liver Cv-aCO2/Ca-vO2. Methods Post hoc analysis of original data from published experimental studies aimed to address effects of different fluid resuscitation strategies on oxygen transport, lactate metabolism and organ dysfunction in fecal peritonitis and endotoxin infusion, and from animals in cardiac tamponade or hypoxic hypoxia. Systemic and regional hemodynamics, blood flow, lactate uptake, carbon dioxide and oxygen-derived variables were determined. Generalized estimating equations (GEE) were fit to assess contributors to systemic and regional Cv-aCO2/Ca-vO2. Results Median (range) of pooled systemic Cv-aCO2/Ca-vO2 in 64 pigs was 1.02 (0.02 to 3.84). While parameters reflecting regional lactate exchange were variably associated with the respective regional Cv-aCO2/Ca-vO2 ratios, only regional ratios were independently correlated with systemic ratio: renal Cv-aCO2 /Ca-vO2 (β = 0.148, 95% CI 0.062 to 0.234; p = 0.001), spleen Cv-aCO2/Ca-vO2 (β = 0.065, 95% CI 0.002 to 0.127; p = 0.042), gut Cv-aCO2/Ca-vO2 (β = 0.117, 95% CI 0.025 to 0.209; p = 0.013), liver Cv-aCO2/Ca-vO2 (β = − 0.159, 95% CI − 0.297 to − 0.022; p = 0.023), hepatosplanchnic Cv-aCO2/Ca-vO2 (β = 0.495, 95% CI 0.205 to 0.786; p = 0.001). Conclusion In a mixed set of animals in different shock forms or during hypoxic injury, hepatosplanchnic Cv-aCO2/Ca-vO2 ratio had the strongest independent association with systemic Cv-aCO2/Ca-vO2, while no independent association was demonstrated for lactate or hemodynamic variables.

We wanted to determine the influence of total blood volume (BV) and blood lactate quantity on lactate concentrations during incremental exercise. Twenty-six healthy, nonsmoking, heterogeneously trained females (27.5 ± 5.9 ys) performed an incremental cardiopulmonary exercise test on a cycle ergometer during which maximum oxygen uptake (V·O2max), lactate concentrations ([La−]) and hemoglobin concentrations ([Hb]) were determined. Hemoglobin mass and blood volume (BV) were determined using an optimised carbon monoxide-rebreathing method. V·O2max and maximum power (Pmax) ranged between 32 and 62 mL·min−1·kg−1 and 2.3 and 5.5 W·kg−1, respectively. BV ranged between 81 and 121 mL·kg−1 of lean body mass and decreased by 280 ± 115 mL (5.7%, p = 0.001) until Pmax. At Pmax, the [La−] was significantly correlated to the systemic lactate quantity (La−, r = 0.84, p < 0.0001) but also significantly negatively correlated to the BV (r = −0.44, p < 0.05). We calculated that the exercise-induced BV shifts significantly reduced the lactate transport capacity by 10.8% (p < 0.0001). Our results demonstrate that both the total BV and La− have a major influence on the resulting [La−] during dynamic exercise. Moreover, the blood La− transport capacity might be significantly reduced by the shift in plasma volume. We conclude, that the total BV might be another relevant factor in the interpretation of [La−] during a cardio-pulmonary exercise test.

Objective: This study aimed to measure blood flow changes in the superior mesenteric artery (SMA), using Doppler ultrasound, in post-cardiac surgery patients, to evaluate the correlation between the SMA resistance index (SMA-RI) and lactate concentrations.Methods: The patients' basic hemodynamics, blood gas parameters and lactate concentration were collected at admission. Simultaneously, the SMA blood flow parameters were collected using Doppler ultrasound with the patients in the supine position. The lactate concentrations were measured again at 2, 6, and 12-h time points after the first test. The length of intensive care unit stays and prognoses continued to be monitored.Results: A total of 67 patients were included. The SMA-RI correlated with the admission (r = 0.3117, P = 0.0102), 2-h (r = 0.5091, P < 0.0001), 6-h (r = 0.5061, P < 0.0001), and 12-h (r = 0.2483, P = 0.0428) lactate concentrations. The SMA-RI could predict the 2-h 10% [area under the curve (AUC) = 0.8294, P < 0.0001] and 6-h 40% lactate kinetics (AUC = 0.7708, P = 0.0012). The cut-off value was 0.83. When the SMA-RI was 10% lactate kinetics, and 64.71 and 75.00%, respectively, for the prediction of the 6-h >40% lactate kinetics. The lactate concentrations at admission, 2 and 6-h points were higher in the high-RI group (RI ≥ 0.83) and the intensive care unit stays were significantly longer than in the low-RI group (P = 0.0005).Conclusions: The increase in SMA-RI was associated with higher lactate concentrations and worse lactate kinetics in post-cardiac surgery patients. This may be related to intestinal hypoperfusion. The SMA-RI may be one of the indicators that should be monitored to guide resuscitation in these patients.

Abstract Background Plasma lactate concentrations and their trends over time are used for clinical prognosis, and to guide treatment, in critically ill patients. Although heavily relied upon for clinical decision-making, lactate kinetics of these patients is sparsely studied. Aim To establish and validate a feasible method to study lactate kinetics in critically ill patients. Methods Healthy volunteers (n = 6) received a bolus dose of 13C-labeled lactate (20 μmol/kg body weight), and 43 blood samples were drawn over 2 h to determine the decay in labeled lactate. Data was analyzed using non-compartmental modeling calculating rates of appearance (R a) and clearance of lactate. The area under the curve (AUC) was calculated using a linear-up log-down trapezoidal approach with extrapolation beyond 120 min using the terminal slope to obtain the whole AUC. After evaluation, the same protocol was used in an unselected group of critically ill patients (n = 10). Results R a for healthy volunteers and ICU patients were 12.8 ± 3.9 vs 22.7 ± 11.1 μmol/kg/min and metabolic clearance 1.56 ± 0.39 vs 1.12 ± 0.43 L/min, respectively. ICU patients with normal lactate concentrations showed kinetics very similar to healthy volunteers. Simulations showed that reducing the number of samples from 43 to 14 gave the same results. Our protocol yielded results on lactate kinetics very similar to previously published data using other techniques. Conclusion This simple and user-friendly protocol using an isotopically labeled bolus dose of lactate was accurate and feasible for studying lactate kinetics in critically ill ICU patients. Trial registration ANZCTR, ACTRN12617000626369, registered 8 March 2017. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372507&isReview=true

Purpose: To investigate association of static and dynamic lactate indices with early mortality (within 48 hours of admission), as well as need for vasopressors and mechanical ventilation in pediatric severe sepsis/shock. To explore optimal cutoffs of lactate indices. We hypothesized that dynamic indices are superior to static indices in predicting early mortality. Methods: This prospective cohort study involved children (aged <14 years) admitted in emergency department, tertiary care teaching hospital in North India with severe sepsis/shock (2015-2016). Arterial lactate was measured at admission (X0) and after 6 hours (X6). Primary outcome of the measurement was early mortality. Association between lactate indices--lactate at 0 hours (Lac0), lactate after 6 hours (Lac6), time-weighted average (LacTW), delta (DLac), clearance (LacCl%) and early mortality, need for vasopressors, and mechanical ventilation--was assessed using Student t test/Mann-Whitney test. Area under the receiver operating characteristic curve (AUROC) for early mortality deduced for all lactate indices and compared with reference (Lac0). Optimal cutoffs (maximizing both sensitivity and specificity) and their positive predictive value (PPV) and negative predictive value (NPV) were determined. Results: During the study period, 116 children were assessed. Septic shock was present at admission in 56.9% children; 50% of children died during the next 48 hours. Lac0, Lac6, and LacTW were significantly higher, and LacCl% was lower in nonsurvivors versus survivors (all P < .001). Lac6 (0.837 [0.76-0.91]) had significantly higher AUROC (95% confidence interval) than Lac0 (0.77; P = .03). Abnormal lactate metrics (higher Lac0, Lac6, LacTW, and lower LacCl%) were associated with vasopressors need and mechanical ventilation. On logistic regression, Lac6 emerged as an independent predictor of early mortality as well as vasopressor and mechanical ventilation need. The optimal cutoff of Lac6 for identifying early mortality with good sensitivity, specificity, PPV, and NPV was ≥2.65 (76, 85, 83, 78). Conclusions: Lactate6 is the best marker associated with early mortality and higher level of care in severe sepsis/septic shock in resource-poor regions. [ABSTRACT FROM AUTHOR]

Background: To investigate the optimal target e of lactate kinetics at different time during the resuscitation, the factors that influence whether the kinetics achieve the goals, and the clinical implications of different clinical phenotypes. Methods: Patients with hyperlactatemia between May 1, 2013 and December 31, 2018 were retrospectively analyzed. Demographic data, basic organ function, hemodynamic parameters at ICU admission (T0) and at 6 h, 12 h, 24 h, 48 h, and 72 h, arterial blood lactate and blood glucose levels, cumulative clinical treatment conditions at different time points and final patient outcomes were collected. Results: A total of 3298 patients were enrolled, and the mortality rate was 12.2%. The cutoff values of lactate kinetics for prognosis at 6 h, 12 h, 24 h, 48 h, and 72 h were 21%, 40%, 57%, 66%, and 72%. The APACHE II score, SOFA score, heart rate (HR), and blood glucose were risk factors that correlated with whether the lactate kinetics attained the target goal. Based on the pattens of the lactate kinetics, eight clinical phenotypes were proposed. The odds ratios of death for clinical phenotypes VIII, IV, and II were 4.39, 4.2, and 5.27-fold of those of clinical phenotype I, respectively. Conclusion: Stepwise recovery of lactate kinetics is an important resuscitation target for patients with hyperlactatemia. The APACHE II score, SOFA score, HR, and blood glucose were independent risk factors that influenced achievement of lactate kinetic targets. The cinical phenotypes of stepwise lactate kinetics are closely related to the prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background A decrease in blood lactate levels (Lac) >10% during the first hours of resuscitation in sepsis is associated with better outcomes, but the mechanisms are unclear. Our objective was to investigate the relationship between the time course of Lac, inflammatory response, and mitochondrial respiration during experimental sepsis. Methods Original data from two previously published studies were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n = 8 each). Animals were categorized according to the decrease in Lac during the first 6 h of resuscitation (early if ≥10% [Lac ≥10%] or late if 10% during early resuscitation (6 h) after abdominal sepsis is associated with lower levels of plasma interleukin-6 and improved brain but not hepatic or muscle mitochondrial respiration. Blood flow redistribution to abdominal organs in animals with early decrease in Lac concentrations increases the potential to both deliver and extract Lac.

Background: Plasma lactate concentrations and their trends over time are used for clinical prognosis, and to guide treatment, in critically ill patients. Although heavily relied upon for clinical decision-making, lactate kinetics of these patients is sparsely studied.Aim: To establish and validate a feasible method to study lactate kinetics in critically ill patients.Methods: Healthy volunteers (n = 6) received a bolus dose of 13C-labeled lactate (20 μmol/kg body weight), and 43 blood samples were drawn over 2 h to determine the decay in labeled lactate. Data was analyzed using non-compartmental modeling calculating rates of appearance (Ra) and clearance of lactate. The area under the curve (AUC) was calculated using a linear-up log-down trapezoidal approach with extrapolation beyond 120 min using the terminal slope to obtain the whole AUC. After evaluation, the same protocol was used in an unselected group of critically ill patients (n = 10).Results: Ra for healthy volunteers and ICU patients were 12.8 ± 3.9 vs 22.7 ± 11.1 μmol/kg/min and metabolic clearance 1.56 ± 0.39 vs 1.12 ± 0.43 L/min, respectively. ICU patients with normal lactate concentrations showed kinetics very similar to healthy volunteers. Simulations showed that reducing the number of samples from 43 to 14 gave the same results. Our protocol yielded results on lactate kinetics very similar to previously published data using other techniques.Conclusion: This simple and user-friendly protocol using an isotopically labeled bolus dose of lactate was accurate and feasible for studying lactate kinetics in critically ill ICU patients.Trial Registration: ANZCTR, ACTRN12617000626369, registered 8 March 2017. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372507&isReview=true. [ABSTRACT FROM AUTHOR]

During a continuously increasing exercise workload (WL) a point will be reached at which arterial lactate accumulates rapidly. This so-called lactate threshold (LT) is associated with the maximal lactate steady state workload (MLSSW), the highest WL, at which arterial lactate concentration [LA] does not change. However, the physiological range in which the LT and the MLSSW occur has not been demonstrated directly. We used minor WL variations in the MLSSW range to assess arterial lactate kinetics in 278 treadmill and 148 bicycle ergometer exercise tests. At a certain workload, minimal further increment of running speed (0.1–0.15 m/s) or cycling power (7–10 W) caused a steep elevation of [LA] (0.9 ± 0.43 mM, maximum increase 2.4 mM), indicating LT achievement. This sharp [LA] increase was more pronounced when higher WL increments were used (0.1 vs. 0.30 m/s, P = 0.02; 0.15 vs. 0.30 m/s, P < 0.001; 7 vs. 15 W, P = 0.002; 10 vs. 15 W, P = 0.001). A subsequent workload reduction (0.1 m/s/7 W) stopped the [LA] increase indicating MLSSW realization. LT based determination of running speed (MLSSW) was highly reproducible on a day-to-day basis (r = 0.996, P < 0.001), valid in a 10 km constant velocity setting (r = 0.981, P < 0.001) and a half marathon race (r = 0.969, P < 0.001). These results demonstrate a fine-tuned regulation of exercise-related lactate metabolism, which can be reliably captured by assessing lactate kinetics at the MLSSW.

International Journal of Exercise Science 12(2): 57-68, 2019. The response of blood lactate concentration (BLC) to exercise is a commonly used approach to set training intensities and to determine the anaerobic threshold, which are important in evaluation of endurance exercise performance. The maximal lactate steady state (MLSS) is defined as the highest workload or BLC that can be maintained without continual lactate accumulation over time. The aim of this study was to investigate MLSS in the cross-country skiing sub-technique double poling and to assess the validity of a fixed blood lactate threshold (OBLA and the 45° tangent of the lactate curve). Eight well-trained cross-country skiers (age = 27.6±8.8 years [mean±SD], body mass = 73.9±6.2 kg, height = 179.3±7.0 cm) performed an incremental test to determine OBLA and Individual Anaerobic Threshold (IAnT) and several constant workload tests of 30 min to determine the MLSS. Lactate concentration at MLSS in double poling was 6.7±1.3 mmol·L-1 which was significantly higher compared to OBLA (p<0.001) and IAnT (p<0.01). Despite significant correlations in velocities between MLSS-IAnT and MLSS-OBLA (r=0.95/0.95, p<0.001), significant (p<0.01) differences between MLSS (21.4±2.8 km·h-1) versus IAnT (20.6±3.6 km·h-1) and OBLA (19.9±3.0 km·h-1) was observed. It was concluded that both OBLA and IAnT underestimate MLSS in double poling. A fixed value of 7 mmol·L-1 would be more appropriate in lactate testing of cross-country skiers using the double poling technique, yet dissuaded because of intra-individual variations. Direct determination of MLSS is the recommended approach for useful exercise thresholds, important for training interventions in elite cross-country skiers. [ABSTRACT FROM AUTHOR]

During a continuously increasing exercise workload (WL) a point will be reached at which arterial lactate accumulates rapidly. This so-called lactate threshold (LT) is associated with the maximal lactate steady state workload (MLSSW), the highest WL, at which arterial lactate concentration [LA] does not change. However, the physiological range in which the LT and the MLSSW occur has not been demonstrated directly. We used minor WL variations in the MLSSW range to assess arterial lactate kinetics in 278 treadmill and 148 bicycle ergometer exercise tests. At a certain workload, minimal further increment of running speed (0.1-0.15 m/s) or cycling power (7-10 W) caused a steep elevation of [LA] (0.9 ± 0.43mM, maximum increase 2.4mM), indicating LT achievement. This sharp [LA] increase was more pronounced when higher WL increments were used (0.1 vs. 0.30 m/s, P = 0.02; 0.15 vs. 0.30 m/s, P < 0.001; 7 vs. 15W, P = 0.002; 10 vs. 15W, P = 0.001). A subsequent workload reduction (0.1 m/s/7 W) stopped the [LA] increase indicating MLSSW realization. LT based determination of running speed (MLSSW) was highly reproducible on a day-to-day basis (r = 0.996, P < 0.001), valid in a 10 km constant velocity setting (r = 0.981, P < 0.001) and a half marathon race (r = 0.969, P < 0.001). These results demonstrate a fine-tuned regulation of exercise-related lactate metabolism, which can be reliably captured by assessing lactate kinetics at the MLSSW. [ABSTRACT FROM AUTHOR]

Background: A decrease in blood lactate levels (Lac) >10% during the first hours of resuscitation in sepsis is associated with better outcomes, but the mechanisms are unclear. Our objective was to investigate the relationship between the time course of Lac, inflammatory response, and mitochondrial respiration during experimental sepsis.Methods: Original data from two previously published studies were reanalyzed. In cohort 1, pigs were randomized to be resuscitated for 48 h starting at 6, 12, and 24 h, respectively, after fecal peritonitis induction (n = 8 each). Animals were categorized according to the decrease in Lac during the first 6 h of resuscitation (early if ≥10% [Lac ≥10%] or late if <10% or increased [Lac <10%]), and systemic hemodynamics, inflammatory parameters, and mitochondrial function were compared between groups. In a second group of animals with fecal peritonitis and 24 h of resuscitation (n = 16, cohort 2), abdominal regional Lac exchange was measured, and animals were categorized according to the decrease in Lac as in cohort 1.Results: Overall mortality was 20% (4 of 20) in the Lac ≥10% group and 60% (12 of 20) in the Lac <10% group (p = 0.022). In cohort 1, systemic hemodynamics were similar in the Lac ≥10% (n = 13) and Lac <10% (n = 11) groups. Plasma interleukin-6 levels increased during unresuscitated sepsis and decreased during resusciation in both groups, but they were lower at study end in the Lac ≥10% group (p = 0.047). Complexes I and II maximal (state 3) and resting (state 4) isolated brain mitochondrial respiration at study end was higher in the Lac ≥10% group than in the Lac <10% group, whereas hepatic, myocardial, and skeletal muscle mitochondrial respiration was similar in both groups. In cohort 2, mesenteric, total hepatic, and renal blood flow at study end was higher in the Lac ≥10% group (n = 7) than in the Lac <10% group (n = 9), despite similar cardiac output. Hepatic lactate influx and uptake in the Lac ≥10% group were approximately 1.5 and 3 times higher, respectively, than in the Lac <10% group (p = 0.066 for both).Conclusions: A decrease in Lac >10% during early resuscitation (6 h) after abdominal sepsis is associated with lower levels of plasma interleukin-6 and improved brain but not hepatic or muscle mitochondrial respiration. Blood flow redistribution to abdominal organs in animals with early decrease in Lac concentrations increases the potential to both deliver and extract Lac. [ABSTRACT FROM AUTHOR]

Background: Setting lactate kinetics at >30% might improve the clinical outcomes of patients with sepsis-associated hyperlactatemia. The aim of this study was to explore the outcome benefits of stepwise lactate kinetics vs central venous oxygen saturation (ScvO2)-oriented hemodynamic therapy at 6 h as the protocol goal during early resuscitation.Methods: The relevant parameters and adverse events after different targets in 360 randomly assigned patients with sepsis-associated hyperlactatemia were recorded and compared.Results: Heart rate (HR) at 48 h in the ScvO2 group was higher than in the lactate kinetics group (105 ± 19 bpm vs 99 ± 20 bpm, P = 0.040). The liquid balance at 4 h, 12 h, and 24 h in the lactate kinetics group was larger than in the ScvO2 group (1535 (1271-1778) ml vs 826 (631-1219) ml, P < 0.001; 1688 (1173-1923) ml vs 1277 (962 - 1588) ml, P <0.001; and 1510 (904-2087) ml vs 1236 (740-1808) ml, P = 0.005), respectively. Mortality was higher in the ScvO2 group (27.9% vs 18.3%, P = 0.033), but there was no significant difference between the two groups in the length of stay in the ICU or mechanical ventilation. In terms of new onset organ dysfunction, there was a significant difference between the two groups in total bilirubin at 48 h and 72 h. Based on the 60-day survival curves, there was significantly more mortality in the ScvO2 group than in the lactate kinetics group (X 2 = 4.133, P = 0.042). In addition, fewer adverse events occurred in the lactate kinetics group.Conclusions: Stepwise lactate kinetics-oriented hemodynamic therapy can reduce mortality in patients with sepsis-associated hyperlactatemia compared with ScvO2-oriented therapy.Trial Registration: National Institutes of Health Clinical Trials Registry, NCT02566460 . Registered on 26 September 2015. [ABSTRACT FROM AUTHOR]

The purpose of this study was to test if the lactate exchange (γ1) and removal (γ2) abilities during recovery following short all-out supramaximal exercise correlate with the muscle content of MCT1 and MCT4, the two isoforms of the monocarboxylate transporters family involved in lactate and H+ co-transport in skeletal muscle. Eighteen lightweight rowers completed a 3-min all-out exercise on rowing ergometer. Blood lactate samples were collected during the subsequent passive recovery to assess an individual blood lactate curve (IBLC). IBLC were fitted to the bi-exponential time function: La(t) = [La](0) + ...) where [La](0) is the blood lactate concentration at exercise completion and the velocity constants γ1 and γ2 denote the lactate exchange and removal abilities, respectively. An application of the bi-compartmental model of lactate distribution space allowed estimation of the lactate removal rate at exercise completion [LRR(0)]. Biopsy of the right vastus lateralis was taken at rest to measure muscle MCT1 and MCT4 content. Fiber type distribution, activity of key enzymes and capillary density (CD) were also assessed. γ1 was correlated with [La](0) (r = -0.54, P < 0.05) but not with MCT1, MCT4 or CD. γ2 and LRR(0) were correlated with MCT4 (r = 0.63, P < 0.01 and r = 0.73, P < 0.001, respectively) but not with MCT1 or cytochrome c oxidase activity. These findings suggest that the lactate exchange ability is highly dependent on the milieu so that the importance of the muscle MCT1 and MCT4 content in γ1 was hidden in the present study. Our results also suggest that during recovery following all-out supramaximal exercise in well-trained rowers, MCT4 might play a significant role in the distribution and delivery of lactate for its subsequent removal. [ABSTRACT FROM AUTHOR]

To examine the influence of aerobic and anaerobic indices on repeated sprint (RS) performance and ability (RSA), 8 sprinters (SPR), 8 endurance runners (END), and 8 active participants (ACT) performed the following tests: ( i) incremental test; ( ii) 1-min test to determine first decay time constant of pulmonary oxygen uptake off-kinetics and parameters related to anaerobic energy supply, lactate exchange, and removal abilities from blood lactate kinetics; and ( iii) RS test (ten 35-m sprints, departing every 20 s) to determine best (RSbest) and mean (RSmean) sprint times and percentage of sprint decrement (%Dec). While SPR had a 98%-100% likelihood of having the fastest RSbest (Cohen's d of 1.8 and 1.4 for ACT and END, respectively) and RSmean (2.1 and 0.9 for ACT and END, respectively), END presented a 97%-100% likelihood of having the lowest %Dec (0.9 and 2.2 for ACT and SPR, respectively). RSmean was very largely correlated with RSbest ( r = 0.85) and moderately correlated with estimates of anaerobic energy supply ( r = -0.40 to -0.49). RSmean adjusted for RSbest (which indirectly reflects RSA) was largely correlated with lactate exchange ability ( r = 0.55). Our results confirm the importance of locomotor- and anaerobic-related variables to RS performance, and highlight the importance of disposal of selected metabolic by-products to RSA. [ABSTRACT FROM AUTHOR]

To verify the effects of training status and blood lactate concentration (BLC) responses on the early excess postexercise oxygen consumption (EPOC), 8 sprinters, 7 endurance runners, and 7 untrained subjects performed an incremental test to determine maximal oxygen uptake and a 1-min all-out test to determine BLC and oxygen uptake recovery curves. BLC kinetics was evaluated to assess the quantity of lactate accumulated during exercise ( QlaA), lactate removal ability ( k2), and quantity of lactate removed from 0 to 10 min postexercise ( QlaR). Oxygen uptake off-kinetics was evaluated to assess the decay time constants (τ1 and τ2); moreover, EPOC was measured during the first 10 min after exercise. While sprinters had 98%-100% and 94%-100% likelihood of having the highest EPOC and decay time constants, endurance runners had 98%-100% and 95%-100% likelihood of having the lowest EPOC and decay time constants. EPOC was correlated with QlaA ( r = 0.74) and QlaR ( r = 0.61). τ1 and τ2 were correlated with maximal oxygen uptake ( r > -0.57), k2 ( r > -0.48), and QlaR relative to QlaA ( r > -0.60). Our findings indicate that oxygen uptake recovery is associated with fast lactate removal and aerobic training. Furthermore, the metabolites derived from anaerobic energy production seem to induce a greater EPOC after all-out exercise. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to predict aerobic and anaerobic capacities using relative changes of arterial blood lactate during the isocapnic buffering phase in male professional cyclists. Researchers evaluated lactate threshold and bicarbonate buffering in six sprint trained cyclists and eight endurance trained cyclists. They found that the lactate and buffering were lower for endurance cyclists than for sprint cyclists and that measuring buffering was useful in evaluating aerobic and anaerobic capacities during exercise.

Abstract: Patients with mitochondrial DNA mutations often have elevated plasma lactate at rest and during exercise, but it is unknown whether the high lactate levels are caused by a high production, an impaired oxidation or a combination. We studied lactate kinetics in 10 patients with mtDNA mutations and 10 matched healthy control subjects at rest and during cycle exercise with a combination of femoral arterio-venous differences of lactate, and lactate tracer dilution methodology. During exercise, lactate concentration and production rates were several-fold higher in patients, but despite mitochondrial dysfunction, lactate was oxidized in muscle to the same extent as in healthy control subjects. This surprisingly high ability to burn lactate in working muscle with defective mitochondria, probably relates to the variability of oxidative capacity among muscle fibers. The data suggests that lactate is not solely an indicator of impaired oxidative capacity, but an important fuel for oxidative metabolism, even in muscle with severely impaired mitochondrial function. [Copyright &y& Elsevier]

We examined the effects of inspiratory muscle training (IMT) upon volitional hyperpnoea-mediated increases in blood lactate ([lac]) during cycling at maximal lactate steady state (MLSS) power, and blood lactate and oxygen uptake kinetics at the onset of exercise. Twenty males formed either an IMT ( n = 10) or control group ( n = 10). Prior to and following a 6-week intervention, two 30 min trials were performed at MLSS (207 ± 28 W), determined using repeated 30 min constant power trials. The first was a reference trial, whereas during the second trial, from 20 to 28 min, participants mimicked the breathing pattern commensurate with 90% of the maximal incremental exercise test minute ventilation ( $$ \dot{V}_{\text{E}} $$). Prior to the intervention, the MLSS [lac] was 3.7 ± 1.8 and 3.9 ± 1.6 mmol L in the IMT and control groups, respectively. During volitional hyperpnoea, $$ \dot{V}_{\text{E}} $$ increased from 79.9 ± 9.5 and 76.3 ± 15.4 L min at 20 min to 137.8 ± 15.2 and 135.0 ± 19.7 L min in IMT and control groups, respectively; [lac] concurrently increased by 1.0 ± 0.6 (+27%) and 0.9 ± 0.7 mmol L (+25%), respectively ( P < 0.05). Following the intervention, maximal inspiratory mouth pressure increased 19% in the IMT group only ( P < 0.01). Following IMT only, the increase in [lac] during volitional hyperpnoea was abolished ( P < 0.05). In addition, the blood lactate (−28%) and phase II oxygen uptake (−31%) kinetics time constants at the onset of exercise and the MLSS [lac] (−15%) were reduced ( P < 0.05). We attribute these changes to an IMT-mediated increase in the oxidative and/or lactate transport capacity of the inspiratory muscles. [ABSTRACT FROM AUTHOR]

This study aimed to determine metabolic and respiratory adaptations during intense exercise and improvement of long-sprint performance following six sessions of long-sprint training. Nine subjects performed before and after training (1) a 300-m test, (2) an incremental exercise up to exhaustion to determine the velocity associated with maximal oxygen uptake ( v- VO), (3) a 70-s constant exercise at intensity halfway between the v- VO and the velocity performed during the 300-m test, followed by a 60-min passive recovery to determine an individual blood lactate recovery curve fitted to the bi-exponential time function: $$ {\text{La}}\left( t \right) = {\text{La}}\left( 0 \right) + A_{ 1} ( 1- {\text{e}}^{{ - \gamma_{{ 1 } }}^{{t}}} ) +\; A_{ 2} ( 1- {\text{e}}^{{ - \gamma_{{ 2 }} }^{{t}}} ) $$, and blood metabolic and gas exchange responses. The training program consisted of 3-6 repetitions of 150-250 m interspersed with rest periods with a duration ratio superior or equal to 1:10, 3 days a week, for 2 weeks. After sprint training, reduced metabolic disturbances, characterized by a lower peak expired ventilation and carbon dioxide output, in addition to a reduced peak lactate ( P < 0.05), was observed. Training also induced significant decrease in the net amount of lactate released at the beginning of recovery ( P < 0.05), and significant decrease in the net lactate release rate (NLRR) ( P < 0.05). Lastly, a significant improvement of the 300-m performance was observed after training. These results suggest that long-sprint training of short durations was effective to rapidly prevent metabolic disturbances, with alterations in lactate accumulation and gas exchange, and improvement of the NLRR. Furthermore, only six long-sprint training sessions allow long-sprint performance improvement in active subjects. [ABSTRACT FROM AUTHOR]

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 primedcontinuous 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 ([...]) [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 ([...] - [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 (... 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. [ABSTRACT FROM AUTHOR]

Background: We have previously demonstrated lactate release by the liver itself in hepatectomies performed under selective hepatic vascular exclusion. We hypothesized that ischemic preconditioning applied in this setting might lead to a reduction of hepatic lactate production.Methods: Twenty-one patients underwent hepatectomy under inflow and outflow occlusion combined with ischemic preconditioning (IP group, n = 21). These patients were matched 1:1 with patients subjected to the same technique of hepatectomy under vascular occlusion without ischemic preconditioning (control group, n = 21). The transhepatic lactate gradient (hepatic vein-portal vein) was calculated before liver dissection and 60 min post-reperfusion.Results: In the control group, the transhepatic lactate gradient before liver resection was negative indicating consumption by the liver. After 60 min post-reperfusion, this gradient became positive, indicating net lactate production by the liver (0.2 ± 0.3 vs. -0.3 ± 0.2 mmol/L, P < 0.001). In the IP group, the liver consumed lactate both before resection and 60 min post-reperfusion (gradients -0.2 ± 1.1 and -0.1 ± 0.6 mmol/L, respectively). The magnitude of lactate release by the liver correlated with systemic hyperlactatemia post-reperfusion and 24 h postoperatively (r(2) = 0.54, P < 0.001 and r(2) = 0.67, P < 0.001, respectively). Significant correlations between the transhepatic lactate gradient post-reperfusion and peak postoperative AST as well as the apoptotic response of the liver remnant were also demonstrated (r(2) = 0.72, P < 0.001 and r(2) = 0.66, P < 0.001, respectively).Conclusion: The microcirculatory derangement and cellular aerobic metabolism breakdown elicited by ischemia-reperfusion insults can be prevented with hepatoprotective measures such as ischemic preconditioning. The transhepatic lactate gradient could act as a monitoring and prognostic tool of the efficacy of ischemic preconditioning. [ABSTRACT FROM AUTHOR]

Current understanding of lactate metabolism in fish is based almost entirely on the interpretation of concentration measurements that cannot be used to infer changes in flux. The goals of this investigation were: (1) to quantify baseline lactate fluxes in rainbow trout (Oncorhynchus mykiss) under normoxic conditions; (2) to establish how changes in rates of lactate appearance (Ra) and disposal (Rd) account for the increase in blood lactate elicited by hypoxia; and (3) to identify the tissues responsible for lactate production. Ra and Rd lactate of rainbow trout were measured in vivo by continuous infusion of [U-14C]lactate in trout exposed to 25% O2 saturation or maintained in normoxia for 90mm. In normoxic fish, Ra lactate decreased from 18.2 to 13.1 μmol kg-1 min-1 and Rd lactate from 19.0 to 12.8. Ra and Rd were always matched, thereby maintaining a steady baseline blood lactate concentration of ∼0.8 mmol l-1. By contrast, the hypoxic fish increased blood lactate to 8.9mmol l-1 and Ra lactate from 18.4 to 36.5 μmol kg-1 min-1. This stimulation of anaerobic glycolysis was unexpectedly accompanied by a 52% increase in Rd lactate from 19.9 to 30.3μmol kg-1 min-1. White muscle was the main producer of lactate, which accumulated to 19.2 μmol g-1 in this tissue. This first study of non-steady-state lactate kinetics in fish shows that the increase in lactate disposal elicited by hypoxia plays a strategic role in reducing the lactate load on the circulation. Without this crucial response, blood lactate accumulation would double. [ABSTRACT FROM AUTHOR]

We evaluated: the agreement between lactate minimum and maximal lactate steady state (MLSS) cycling powers (study 1); whether rates of change of blood lactate concentration during the lactate minimum test reflect that of constant power exercise (study 2); whether the lactate minimum power is influenced by the muscle groups used to elevate blood lactate concentration (study 3). Study 1: 32 subjects performed a lactate minimum test comprising a lactate elevation phase, recovery phase, and incremental phase (five 4 mm stages); MLSS was subsequently determined. Study 2: 8 subjects performed a lactate minimum test and five 22 min constant power tests at the incremental phase exercise intensities. Study 3: 10 subjects performed two identical lactate minimum tests, except during the second test the lactate elevation phase comprised arm-cranking. Lactate minimum and MLSS powers demonstrated good agreement (mean bias±95% limits of agreement: 2±22 W). Rates of change of blood lactate concentration during each incremental phase stage and corresponding constant power test did not correlate. Lactate minimum power was lowered when arm-cranking was used during the lactate elevation phase (157±29 vs. 168±21 W; p<0.05). The lactate elevation phase modifies blood lactate concentration responses during the incremental phase, thus good agreement between lactate minimum and MLSS powers seems fortuitous. [ABSTRACT FROM AUTHOR]

The effects of a 7 d high-fructose diet (HFrD) or control diet on lipid metabolism were studied in a group of six healthy lean males. Plasma NEFA and β-hydroxybutyrate concentrations, net lipid oxidation (indirect calorimetry) and exogenous lipid oxidation (13CO2 production) were monitored in basal conditions, after lipid loading (olive oil labelled with [13C]triolein) and during a standardised mental stress. Lactate clearance and the metabolic effects of an exogenous lactate infusion were also monitored. The HFrD lowered plasma concentrations of NEFA and β-hydroxybutyrate as well as lipid oxidation in both basal and after lipid-loading conditions. In addition, the HFrD blunted the increase in plasma NEFA and exogenous lipid oxidation during mental stress. The HFrD also increased basal lactate concentrations by 31·8 %, and lactate production by 53·8 %, while lactate clearance remained unchanged. Lactate infusion lowered plasma NEFA with the control diet, and net lipid oxidation with both the HFrD and control diet. These results indicate that a 7 d HFrD markedly inhibits lipolysis and lipid oxidation. The HFrD also increases lactate production, and the ensuing increased lactate utilisation may contribute to suppress lipid oxidation. [ABSTRACT FROM PUBLISHER]

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 l-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 l-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]