Increased Blood Lactate Research Articles

Unlocking the full potential of resistance training: a comparative analysis of low- and high-intensity effects on neurotrophic growth factors and homocysteine

ObjectiveResistance training has been demonstrated an effective approach for preventing the cognitive function decline through physiological mechanisms; however, the effect of acute resistance training at different intensities on growth factor and homocysteine levels remains unclear. This study aimed to compare the impact of resistance training at varying intensities on peripheral neurobiological factors and homocysteine levels in young adults.MethodsTwelve young male adults, predominantly engaged in various sports activities but without prior strength training experience, were recruited to participate in a randomized controlled cross-over trial. They implemented two different resistance training protocols: high intensity (HIRT, 12 repetitions at 80% 1RM) and low intensity (LIRT, 24 repetitions at 40% 1RM). Blood samples were collected at three time points: pre-training, post training, and after 30 min of rest to measure changes in serum lactate, serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), irisin, and plasma homocysteine (Hcy) levels.ResultsBoth resistance training protocols significantly increased blood lactate and perceived exertion compared to pre-training (HIRT, p < 0.01; LIRT, p < 0.01), with higher levels observed in HIRT. Acute HIRT significantly elevated serum BDNF, IGF-1, and VEGF levels post training compared to LIRT (p < 0.05), while no difference was observed in irisin levels between the two protocols at any time point. Both training protocols significantly reduced plasma Hcy levels post training (p < 0.01) and maintained lower levels than pre-training and after 30 min of rest (p < 0.05), with no significant differences between the two protocols.ConclusionsThis study demonstrates that high intensity training appears to have a greater impact on specific neurobiological factors; however, regardless of intensity, resistance training can significantly decrease plasma homocysteine.Trial registration ClinicalTrials.gov ID: NCT06114550. Date of registration 01/30/2024. https://clinicaltrials.gov/study/NCT06114550.

Intracardiac abscess in the clinical course of infective endocarditis complicated by acute heart failure

Background. Infective endocarditis (IE) remains a serious condition with a high incidence rate, ranging from 2.6 to 7 cases per 100,000 people, and has been increasing over recent decades. Intracardiac abscess (ICA) is one of the most severe complications of infective endocarditis, occurring in 30–40 % of cases involving native heart valves. Heart failure, the most common complication, is observed in 19–73 % of patients and often requires urgent surgical intervention. Objective: to determine the optimal diagnostic and treatment algorithm for patients with infective endocarditis complicated by acute heart failure (AHF) and intracardiac abscess. Materials and methods. From 2010 to 2023, at the Amosov National Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine, 473 surgeries were performed for active infectious endocarditis complicated by intracardiac abscesses, accounting for 15 % of all cases of IE. A comprehensive approach was used, including autopericardial patches, abscess debridement, reconstruction of the heart chambers, fibrous ring repair, valve replacement, and methods for preventing recurrences. Results. The patients were divided into two groups: ICA with AHF (N = 135, 28.5 %) and ICA without AHF (N = 338, 71.5 %). The average age of participants was 49.2 ± 1.2 years. In the overall group, procalcitonin and C-reactive protein levels were evaluated to characterize the inflammatory process. The inflammatory markers included leukocyte count, elevated erythrocyte sedimentation rate, and levels of C-reactive protein and procalcitonin. High levels of these markers indicate signs of persistent infection syndrome, immunosuppression, and catabolism. Increased blood lactate levels suggest tissue hypoxia and organ dysfunction. Acute heart failure was characterized by elevated levels of NT-proBNP, troponin, and creatine phosphokinase-MB. One hundred and thirty-five (28.5 %) infective endocarditis patients with ICA and signs of AHF at the preoperative stage of IV FC formed the study group. Conclusions. Successful treatment of IE depends on early surgical intervention and effective antibiotic therapy. Early detection of complications such as AHF and intracardiac abscesses is critically important. Autopericardial patches and modern surgical techniques significantly improve patient outcomes. Elevated markers such as NT-proBNP, troponin, C-reactive protein, procalcitonin, and lactate indicate the severity of the condition.

Study of Blood Lactate Levels at Admission as a Predictor of Mortality and Morbidity in Critically Ill Children in a Tertiary Care Pediatric Intensive Care Unit

Background and Aim: Patients with severe illness are at an elevated risk of experiencing multiple organ failure, which in turn increases their likelihood of mortality. Hyperlactatemia is recognized as a distinct risk factor for the onset of organ dysfunction and mortality, as well as morbidity in children’s. Present study aims to to determine threshold values for the prediction of in-hospital mortality in the larger cohort of critically ill children and to evaluate the predictive value of blood lactate levels at admission. Methods: This prospective observational study was conducted with 202 critically ill children, ranging in age from one month to 18 years, admitted to the Pediatric Intensive Care Unit (PICU). Arterial blood samples were obtained upon admission, and subsequent measurements of lactate levels were conducted. The demographical data, clinical status and organ involvement were recorded. Statistical analysis was performed by using SPSS Version 21.0 and P &lt; 0.05 was considered to be significant. Results: Survivors geometric mean lactate levels at admission were lower (1.2 mmol/L) than non-survivors' (4.8 mmol/L), and higher lactate levels at admission were substantially linked to both mortality and morbidity (length of hospital stay, need for ventilator and inotropic support). The sensitivity and specificity of the blood lactate levels were 93.6% and 89.7%, achieved at the optimal cut-off value of 4.05 mmol/L. The incidence of multi organ dysfunction, need for ventilator and inotropic support, duration of hospital stay in critically ill children was significantly associated with increased blood lactate levels at admission (P&lt;0.01). Conclusion: A high level of blood lactate upon admission was independently predictive of in-hospital mortality in the pediatric population. The early identification of children who are at a high risk for mortality allows for prompt intervention, thereby enhancing the overall outcomes.

Acute Responses of Low-Load Resistance Exercise with Blood Flow Restriction.

Blood flow restriction (BFR) is a popular resistance exercise technique purported to increase metabolic stress and augment training adaptations over time. However, short-term use may lead to acute neuromuscular fatigue and higher exertion ratings. Objective: The purpose of the current study was to examine acute physiological responses to low-load resistance exercise utilizing BFR compared to higher-load, non-BFR resistance exercise. Methods: Recreationally trained males (n = 6) and females (n = 7) (mean ± standard deviation, age: 20 ± 1 yrs.; height: 172 ± 8 cm; weight: 73 ± 11 kg; BMI: 24.4 ± 2.2 kg·m-2; training experience: 4 ± 2 yrs.) had limb occlusion pressure determined (50%; right leg: 118 ± 11 mmHg; left leg: 121 ± 13 mmHg) using an automated, self-inflating cuff system during baseline testing. In subsequent sessions, using a randomized, cross-over design, participants completed one of two experimental conditions: (1) Low-load + BFR and (2) High load + non-BFR. In both conditions, participants completed one set of back squats at either 30% (BFR) or 60% (non-BFR) of an estimated 1RM for a max of 30 repetitions, followed by three additional sets with the same loads and a target of 15 repetitions per set. Blood lactate and countermovement jump (CMJ) height were measured pre- and post-back squat. Ratings of perceived exertion (RPE) were assessed following each set. Results: When collapsed across all sets, participants completed significantly more total repetitions in the BFR condition compared to non-BFR (75.0 ± 0.0 vs. 68.23 ± 9.27 reps; p = 0.015; ES: 1.03), but a lower training load volume (2380 ± 728 vs. 4756 ± 1538 kg; p < 0.001; ES: 1.97). There was a significant time-by-condition interaction (p < 0.001), with a greater increase in blood lactate occurring from baseline to post-back squat in the non-BFR condition (11.61 mmol/L, 95%CI: 9.93, 13.28 mmol/L) compared to BFR (5.98 mmol/L, 95%CI: 4.30, 7.65 mmol/L). There was another significant time-by-condition interaction (p = 0.043), with a greater reduction in CMJ occurring in the non-BFR condition (-6.01, 95%CI: -9.14, -2.88 cm; p < 0.001) compared to BFR (-1.50, 95%CI: -1.50, 4.51 cm; p = 0.312). Conclusions: Utilizing a low-load BFR protocol may allow for a higher training volume, yet lower metabolic stress and reduce neuromuscular fatigue compared to lifting at a higher load without the use of BFR.

Temporal evaluation of lung injury following chlorine Inhalation in a ventilated pig model

Objective Chlorine (Cl2) is a widely used industrial chemical and toxic human exposures have occurred from Cl2 releases. No approved medical countermeasures (MCMs) exist for Cl2-induced lung injuries. The objective of this study was to develop and characterize swine Cl2 inhalation injuries to understand lung injury and histopathological sequalae. Materials and methods Male swine (approximately 14 weeks old) were anesthetized, paralyzed, intubated, and exposed to clean air or Cl2 while connected to a ventilator. The exposed LD50/24 hr of 1.8 mg/kg was delivered within a 15–20-minute timeframe. Scheduled terminal timepoints were 6 h, 7- and 30-days post-exposure. Results Following Cl2 exposure, 46% of the animals succumbed with an average time to death of 1.42 h. Dynamic lung compliance at 6 h post-exposure was reduced 45%. Clinical observations demonstrated respiratory abnormalities similar to Cl2 exposed humans. Compared to air shams, Cl2-exposed animals had decreased SpO2, arterial blood pH, pO2, sO2, increased blood lactate levels and deoxyhemoglobin levels at early timepoints. Increased neutrophils 6 h post- exposure occurred concurrent with increased inflammatory cytokines, bronchiolar epithelial necrosis with alveolar edema, cellular infiltrates, and lobular atelectasis. Discussion/Conclusions Potentially relevant biomarkers involved in the progression and recovery from acute Cl2 lung injury in this model include lung compliance, select cytokines/chemokines, arterial blood gas parameters, and histopathological evaluation. Normal lung histopathological observations beyond 7- days indicates that histopathological evaluations should occur earlier. This animal model delivers accurate and consistent Cl2 exposures resulting in a human-relevant lung injury for evaluating MCM efficacy against Cl2-mediated acute lung injury.

Oral sodium lactate ingestion does not increase blood lactate concentrations and is accompanied by moderate-to-severe gastrointestinal side effects.

Lactate has diverse roles in biology and has been implicated in the control of energy intake. A variety of methods (i.e., exercise, ingestion, and infusion) have been used to study its effects on different metabolic outcomes and the original intent of this project was to explore the effect of oral sodium lactate (Na-Lactate) ingestion on appetite regulation. During piloting, we were unable to show that Na-Lactate could increase blood lactate concentrations; thus, the purpose of this brief report is to highlight that oral Na-Lactate ingestion is not an effective method to study lactate metabolism. Five male participants (26 ± 3 yr, 82.4 ± 3.8 kg, 25.4 ± 1.6 kg·m-2) completed 15 experimental sessions where Na-Lactate solutions were consumed with the assessment of blood lactate preingestion, 30-min, 45-min, and 60-min postingestion. Oral Na-Lactate ingestion did not increase blood lactate concentrations (Pre: 0.9 ± 0.2; 30 min: 1.2 ± 0.7; 45 min: 1.0 ± 0.5; 60 min: 0.9 ± 0.4 mmol·L-1). In addition, there were moderate-to-severe gastrointestinal (GI) side effects (e.g., vomiting and diarrhea) following ingestion. Altogether, our data suggest that oral ingestion of Na-Lactate is not an effective method for studying lactate's role in metabolism as it did not increase blood lactate concentrations and was accompanied by problematic GI side effects.NEW & NOTEWORTHY Lactate has diverse roles in physiology, and a variety of methods have been used to explore its effects on metabolism. Here, we explored whether oral sodium lactate (Na-Lactate) ingestion could increase blood lactate concentrations. Oral Na-Lactate ingestion using a variety of dosing protocols did not increase blood lactate concentrations and was coupled with gastrointestinal issues. These results demonstrate that oral ingestion of Na-Lactate is not an effective method for studying lactate's role in metabolism.

The Effect of Transcranial Direct Current Stimulation on Lower-Limb Endurance Performance: A Systematic Review.

This study systematically reviews the literature on transcranial direct current stimulation (tDCS) interventions for lower-limb endurance performance in healthy adults and provides a summary of the effects and underlying mechanisms of tDCS on lower-limb endurance performance. Systematic searches were performed in PubMed, Web of Science, EBSCO, and ScienceDirect. The risk of bias was assessed using the Cochrane risk of bias assessment tool. The electronic search totaled 341 studies. Twenty-one studies were included in the review after screening. The results show that tDCS effectively improved time to task failure (TTF), increased blood lactate accumulation, and reduced the rating of perceived exertion during cycling. However, the tDCS failed to significantly improve the TTF, relieve muscle pain, and reduce fatigue indices during single-joint fatigue tasks in the knee. Moreover, tDCS intervention caused the effective improvement of the overall lower-limb endurance performance but exerted no uniformly conclusive effect on knee endurance performance. This finding can be partly attributed to varying stimulation protocols across studies. Future studies may focus on the effects of the application of stimulation protocols, such as multitarget stimulation and personalized dosage, to develop targeted stimulation protocols.

Exclusion of sulfide:quinone oxidoreductase from mitochondria causes Leigh-like disease in mice by impairing sulfide metabolism.

Leigh syndrome is the most common inherited mitochondrial disease in children and is often fatal within the first few years of life. In 2020, mutations in the gene encoding sulfide:quinone oxidoreductase (SQOR), a mitochondrial protein, were identified as a cause of Leigh syndrome. Here, we report that mice with a mutation in the gene encoding SQOR (SqorΔN/ΔN mice), which prevented SQOR from entering mitochondria, had clinical and pathological manifestations of Leigh syndrome. SqorΔN/ΔN mice had increased blood lactate levels that were associated with markedly decreased complex IV activity and increased hydrogen sulfide (H2S) levels. Because H2S is produced by both gut microbiota and host tissue, we tested whether metronidazole (a broad-spectrum antibiotic) or a sulfur-restricted diet rescues SqorΔN/ΔN mice from developing Leigh syndrome. Daily treatment with metronidazole alleviated increased H2S levels, normalized complex IV activity and blood lactate levels, and prolonged the survival of SqorΔN/ΔN mice. Similarly, a sulfur-restricted diet normalized blood lactate levels and inhibited the development of Leigh syndrome. Taken together, these observations suggest that mitochondrial SQOR is essential to prevent systemic accumulation of H2S. Metronidazole administration and a sulfur-restricted diet may be therapeutic approaches to treatment of patients with Leigh syndrome caused by mutations in SQOR.

CECAL SLURRY AS AN ALTERNATIVE MODEL TO CECAL LIGATION AND PUNCTURE FOR THE STUDY OF SEPSIS-INDUCED CARDIOVASCULAR DYSFUNCTION.

Sepsis is a life-threatening condition widely studied by animal models. Cecal ligation and puncture (CLP) is still regarded as the gold standard model for sepsis. However, CLP has limitations due to its invasiveness and variability. Cecal slurry (CS) model is a nonsurgical and thus less invasive alternative. However, the lack of standardization of the CS model in the literature limits its practical application. Additionally, it is not well studied whether CS model reproduces septic cardiovascular dysfunction in rats, which is a crucial issue in septic patients. Thus, this study aimed to standardize the CS model in Wistar rats and evaluate sepsis-induced cardiovascular dysfunction compared to CLP. Our results showed that CS model induced important features of sepsis cardiovascular dysfunction 24 h after its onset, such as hypotension, tachycardia, and decreased contractile response to vasoconstrictors both in vivo and ex vivo as well changes in renal blood flow. Increases in blood lactate, AST, ALT, creatinine, and urea indicated organ dysfunction. CS model also induced increased production of nitric oxide metabolites and bacterial spread to tissues. CS model causes less animal suffering, it is a nonsurgical model, and, more importantly, it replicates the cardiovascular dysfunction induced by sepsis with better homogeneity than CLP. Therefore, CS model serves as an alternative and possibly as a better model for sepsis research.

Phase I clinical study of FC084CSA, a high selective AXL kinase inhibitor that ameliorates tumor microenvironment and augments the effectivity of immunotherapy.

e15116 Background: NSCLC patients with STK11 gene mutations could not benefit from immunotherapy, according to the data of multiple clinical trials. This is associated with immunosuppressive tumor microenvironment (TME) due to elevated AXL expression, and deficiency in pro-inflammatory cytokines and effector T cells. AXL inhibitor bemcentinib (formerly BGB324) has been found to improve the effectiveness of immunotherapy of immune checkpoint inhibitors. FC084CSA is a high selective AXL inhibitor. Methods: This is an ongoing first-in-human, phase I study of FC084CSA in patients with advanced solid tumors. The primary objective is to evaluate the safety and tolerability of FC084CSA. The secondary objectives include preliminary efficacy and pharmacokinetics. Results: As of January 10th, 2024, 9 patients with a median age of 60 years (44-73) were enrolled in 4 different dose levels: 100mg QD, 200mg QD, 400mg QD and 600mg QD. All patients had ≥ 2 prior lines of prior therapy. No dosing-limiting toxicities were observed. 8 (88.9%) patients experienced treatment-related adverse events (TRAEs). Most TRAEs were grade 1 or 2 and only one grade 3 TRAE was observed. The most common TRAEs (≥20%) included increased blood lactate dehydrogenase (44.4%), elevated gamma-glutamyl transferase (33.3%), proteinuria (33.3%), anemia (33.3%), increased aspartate aminotransferase (22.2%), weight loss (22.2%), increased blood creatinine (22.2%) and vomiting (22.2%). A total of 8 patients had at least 1 post-baseline tumor assessment. Objective response rate (ORR) was 0% and disease control rate (DCR) was 62.5% (5/8). Conclusions: FC084CSA was well tolerated in patients with previously heavily treated solid tumors. Clinical trial information: NCT06231550 .

Influence of Ingestion of Bicarbonate-Rich Water Combined with an Alkalizing or Acidizing Diet on Acid-Base Balance and Anaerobic Performance.

During high-intensity (HI) exercise, metabolic acidosis significantly impairs exercise performance. Increasing the body's buffering capacity through training and exogenous intake of alkalizing supplements may improve high-intensity performance. Manipulating water and diet intake may influence the acid-base balance. The aim of this study was to determine the effects of mineral water rich in bicarbonate ions (STY) or placebo water (PLA) on circulating biomarkers and anaerobic performance and to verify whether alkalizing (ALK) or acidizing (ACI) diet would modulate these effects. Twenty-four athletes, assigned either to ALK (n = 12) or ACI (n = 12) diet for four weeks, completed a 1-min rowing Wingate Test in a double-blind and randomized trial after one week of daily hydration (1.5 to 2L/d) with either STY or PLA. Blood samples were taken before and after each test, and urine samples were collected each week. Chronic consumption of bicarbonate-rich water significantly impacted resting urinary pH irrespective of alkalizing or acidizing dietary intake. STY induced a significant increase in blood pH, lactate, and HCO3 - ion concentration post-exercise compared to PLA. Similar changes were observed when STY was associated with the ALK diet. In contrast, STY combined with the ACI diet only significantly affected urine pH and peak blood lactate compared to PLA (p < 0.05). No effect of bicarbonate-rich water was reported on anaerobic performance (p > 0.05). Our results suggest that consumption of bicarbonate-rich water alters acid-base balance during a warm-up and after HI exercise, could potentiate beneficial effects of an alkalizing diet on the acid-base balance after HI exercise, and reduces the acid load induced by an acidifying diet.

Lactate and hydrogen ions play a predominant role in evoking the exercise pressor reflex during ischaemic contractions but not during freely perfused contractions.

We investigated the role played by lactate and hydrogen in evoking the exercise pressor reflex (EPR) in decerebrated rats whose hindlimb muscles were either freely perfused or ischaemic. Production of lactate and hydrogen by the contracting hindlimb muscles was manipulated by knocking out the myophosphorylase gene (pygm). In knockout rats (pygm-/-; n=13) or wild-type rats (pygm+/+; n=13), the EPR was evoked by isometrically contracting the triceps surae muscles. Blood pressure, tension, blood flow, renal sympathetic nerve activity and blood lactate concentrations were measured. Intramuscular metabolites and pH changes induced by the contractions were quantified by 31P-magnetic resonance spectroscopy (n=5). In a subset of pygm-/- rats (n=5), contractions were evoked with prior infusion of lactate (pH 6.0) in an attempt to restore the effect of lactate and hydrogen ions. Contraction of freely perfused muscles increased blood lactate and decreased muscle pH in pygm+/+ rats only. Despite these differences, the reflex pressor and sympathetic responses to freely perfused contraction did not differ between groups (P=0.992). During ischaemia, contraction increased muscle lactate and hydrogen ion production in pygm+/+ rats (P<0.0134), whereas it had no effect in pygm-/- rats (P>0.783). Likewise, ischaemia exaggerated the reflex pressor, and sympathetic responses to contraction in pygm+/+ but not in pygm-/- rats. This exaggeration was restored when a solution of lactate (pH 6.0) was infused prior to the contraction in pygm-/- rats. We conclude that lactate and hydrogen accumulation in contracting myocytes play a key role in evoking the metabolic component of the EPR during ischaemic but not during freely perfused contractions. KEY POINTS: Conflicting results exist about the role played by lactate and hydrogen ions in evoking the exercise pressor reflex. Using CRISP-Cas9, we rendered the myophosphorylase gene non-functional to block the production of lactate and hydrogen ions. The exercise pressor reflex was evoked in decerebrated rats by statically contracting the triceps surae muscles with or without muscle ischaemia. Static contraction elevated the concentration of lactate and hydrogen ions in pygm+/+ but not in pygm-/- rats. Despite these differences, the exercise pressor reflex was not different between groups. Acute muscle ischaemia exaggerated the concentration of lactate and hydrogen ions in pygm+/+ but not in pygm-/- rats. Likewise, acute muscle ischaemia exaggerated the exercise pressor reflex in pygm+/+ but not in pygm-/- rats. We conclude that lactate and hydrogen play a key role in evoking the exercise pressor reflex during ischaemic but not during freely perfused contractions.

Higher Blood Lactate with Prolongation of Underwater Section in Submaximal Front-Crawl Swimming.

The underwater phase (UP) is highly important for overall swimming performance in most swimming events. However, the metabolic effects of the prolonged UP remain unclear. The purpose of this cross-sectional study was to compare the blood lactate response to submaximal front-crawl swimming with short and extended UP. Twelve (four females) junior competitive swimmers (aged 15.4 (1.4) years) undertook 200 m front-crawl swim trials in a 25 m pool at a pre-determined "anaerobic threshold" velocity on two occasions using short (<5 m) and extended (12.5 m) UP after each turn. Pacing and total time were ensured to be identical between the trials. Capillary blood lactate response was measured. Testing for 25 m swim time with <5 m and 12.5 m UP was conducted on a separate occasion. When athletes undertook and extended UP after each propulsion from the wall, their post-exercise blood lactate concentration reached 7.9 (2.1) mmol/L, more than two times higher than the response to trial with short UP (p < 0.001). All-out 25 m swimming with <5 m or 12.5 m UP disclosed no difference in locomotion velocity (p > 0.05). In conclusion, extending UP of submaximal front-crawl swimming close to maximally allowed during the races substantially increases blood lactate accumulation, i.e., increases the reliance on anaerobic metabolism. Therefore, extended UP is most likely counterproductive for the performance in long-distance swimming, at least for the athletes with a FINA score of <800. On the other hand, the extension of UP could be an effective strategy to train 'lactate tolerance', lactate shuttling, removal, and recycling.

Acute alcohol ingestion decreases the work done above the end-test power during a 3-min all-out cycling exercise.

Alcohol ingestion influences metabolism during a subsequent exercise session, as evidenced by increased blood lactate concentration during fixed-intensity exercise. Therefore, augmented blood concentrations of alcohol may interfere with the anaerobic metabolism during high-intensity, short-duration exercise bout, thereby leading to impaired athletic performance. This study investigated whether the acute ingestion of alcohol as ethanol modulates performance parameters derived from the power-duration relationship in a 3-min all-out cycling test that allows for identifying the power output related to heavy and severe exercise intensities. Twenty-four recreationally active cyclists (16 men and 8 women) ingested a beverage containing either 0.4g ethanol.kg-1 body mass (EtOH) or a placebo (PLA) solution. Thirty minutes following ingestion, they completed a 3-min all-out test to measure power output and determine the end-test power (EP) and the work done above EP (WEP). Alcohol ingestion decreased WEP by 16% (EtOH: 5.6 ± 2.5kJ vs. PLA: 6.7 ± 2.4kJ; P = .003) but did not change EP (EtOH: 211 ± 44W vs. PLA: 212 ± 44W; P = .671). The alcohol-mediated effect in WEP was not influenced when controlling for participants' sex or accuracy in identifying the beverage ingested. Our data indicate that alcohol ingestion impaired the anaerobic work capacity, as evidenced by the reduction in WEP during the 3-min all-out test. Moreover, the ability to exercise at an intensity above the heavy domain may be decreased after ingestion of a moderate alcohol dose.

Anesthetic managements, morbidities and mortalities in retroperitoneal sarcoma patients experiencing perioperative massive blood transfusion.

Given high risks of major bleeding during retroperitoneal sarcoma(RPS) surgeries, severe complications and deaths are common to see perioperatively. Thus, effective anesthetic management is the key point to ensuring the safety of patients. This study aimed to introduce anesthesia management and mortalities in RPS patients receiving massive blood transfusions during surgeries. Records of RPS surgeries under general anesthesia from January 2016 through December 2021 were retrospectively retrieved from our database. Patients who received massive blood transfusions (MBT) exceeding 20 units in 24h duration of operations were finally included in this study. Demographics, modalities of anesthesia management, blood loss, transfusion, peri-anesthesia biochemical tests as well as morbidities and mortalities were collected. Risk factors of postoperative 60d mortality were determined through logistic regression in uni-and multi-variety analysis using the statistics software STATA 17.0. A total of 70 patients (male 31) were included. The mean age was 50.1 ± 15.8 years. All patients received combined resections of sarcoma with involved organs under general anesthesia. Mean operation time and anesthesia time were 491.7 ± 131.1mins and 553.9 ± 132.6mins, respectively. The median intraoperative blood loss was 7000ml (IQR 5500,10000ml). Median red blood cells (RBC) and fresh frozen plasma (FFP) transfusion were 25.3u (IQR 20,28u), and 2400ml (IQR 2000,3000ml), respectively. Other blood products infusions included prothrombin complex concentrate (PCCs), fibrinogen concentrate (FC), platelet(plt) and albumin(alb) in 82.9% (58/70), 88.6% (62/70), 81.4% (57/70) and 12.9% (9/70) of patients. The postoperative severe complication rate(Clavien-Dindo grade≥3a) was 35.7%(25/70). A total of 7 patients (10%) died during the postoperative 60-day period. BMI, volumes of crystalloid infusion in anesthesia, and hemoglobin and lactate levels at the termination of operation were found significantly associated with postoperative occurrence of death in univariate analysis. In logistic multivariate analysis, extended anesthesia duration was found associated with postoperative venous thrombosis embolism (VTE) and severe complication. The lactate level at the immediate termination of the operation was the only risk factor related to perioperative death (p<0.05). RPS patients who endure MBT in surgeries face higher risks of death postoperatively, which needs precise and effective anesthesia management in high-volume RPS centers. Increased blood lactate levels might be predictors of postoperative deaths which should be noted.

Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice.

The Olfr78 gene encodes a G-protein-coupled olfactory receptor that is expressed in several ectopic sites. Olfr78 is one of the most abundant mRNA species in carotid body (CB) glomus cells. These cells are the prototypical oxygen (O2) sensitive arterial chemoreceptors, which, in response to lowered O2 tension (hypoxia), activate the respiratory centers to induce hyperventilation. It has been proposed that Olfr78 is a lactate receptor and that glomus cell activation by the increase in blood lactate mediates the hypoxic ventilatory response (HVR). However, this proposal has been challenged by several groups showing that Olfr78 is not a physiologically relevant lactate receptor and that the O2-based regulation of breathing is not affected in constitutive Olfr78 knockout mice. In another study, constitutive Olfr78 knockout mice were reported to have altered systemic and CB responses to mild hypoxia. To further characterize the functional role of Olfr78 in CB glomus cells, we here generated a conditional Olfr78 knockout mouse strain and then restricted the knockout to glomus cells and other catecholaminergic cells by crossing with a tyrosine hydroxylase-specific Cre driver strain (TH-Olfr78 KO mice). We find that TH-Olfr78 KO mice have a normal HVR. Interestingly, glomus cells of TH-Olfr78 KO mice exhibit molecular and electrophysiological alterations as well as a reduced dopamine content in secretory vesicles and neurosecretory activity. These functional characteristics resemble those of CB neuroblasts in wild-type mice. We suggest that, although Olfr78 is not essential for CB O2 sensing, activation of Olfr78-dependent pathways is required for maturation of glomus cells.

Partial Pressure of End-Tidal Oxygen and Blood Lactate During Cardiopulmonary Exercise Testing in Healthy Older Participants and Patients at Risk of Cardiac Disease.

The partial pressure of end-tidal oxygen (PETO2) and end-tidal oxygen concentration (ETO2) are among the indices that can be measured by exhaled gas analysis. Several observational studies have shown that skeletal muscle function is impaired in patients with cardiac disease; thus, the assessment of skeletal muscle function is important. Additionally, although it has recently been suggested that the difference in PETO2 from rest to the ventilatory anaerobic threshold (VAT) reflects oxygen availability in peripheral factors, primarily skeletal muscle, the evidence for this is not well established. Therefore, we hypothesized and investigated whether increased blood lactate (BLa) levels, resulting from decreased skeletal muscle and mitochondrial oxygen availability, and PETO2 dynamics during cardiopulmonary exercise testing (CPET) would be related. All participants performed the symptomatic limited CPET, and their BLa levels were measured. The difference in PETO2 and ETO2 from rest to VAT determined by the V-slope method (ΔPETO2 and ΔETO2) was calculated and compared with the increase in BLa due to exercise testing. We recruited 22 healthy older participants (nine males; 69.4 ± 6.8 years) and 11 patients with cardiovascular risk (eight males; 73.0 ± 8.8 years). ΔPETO2 and ΔETO2 did not differ between the two groups (P = 0.355 and P = 0.369, respectively), showing no correlation between increase in BLa from rest to VAT, but were significantly correlated with an increase in BLa from rest to the end of exercise (ΔPETO2, P = 0.030; ΔETO2, P = 0.029). The correlation was particularly pronounced among those at cardiovascular risk (ΔPETO2, P = 0.012; ΔETO2, P = 0.011). ΔPETO2 and ΔETO2 from rest to VAT during CPET may be useful as indices reflecting skeletal muscle oxygen utilization capacity.

Effects of Caffeine Ingestion on Pulmonary V˙O2 Kinetics and Muscle Fatigue During Severe-Intensity Cycling Exercise.

This study aimed to analyze the effect of caffeine (CAF) intake on pulmonary oxygen uptake (V˙O2) kinetics, muscle fatigue, and physiological and perceptual parameters during severe-intensity cycling exercise. Twelve physically active men (age: 26 ± 5years; V˙O2peak: 46.7 ± 7.8ml·kg-1·min-1) participated of this placebo (PLA)-controlled, randomized, double-blinded, and crossover design study. Participants performed on separate days (a)a ramp incremental test to determine V˙O2peak and gas exchange threshold and (b)four 8-min constant work rate tests at 60% of the difference between gas exchange threshold and maximal V˙O2peak (i.e.,Δ60%) 1hr after taking either 6mg/kg of body mass of CAF or PLA. Before and immediately after constant work rate tests, a 5-s all-out isokinetic sprint was performed to assess the muscle torque. V˙O2 kinetics, blood lactate concentration ([La]), and rating of perceived exertion were analyzed during constant work rate tests. CAF did not alter the primary time constant of V˙O2 kinetics (PLA: 38.3 ± 14; CAF: 36.7 ± 7.5s), V˙O2 slow component (PLA: 0.5 ± 0.2; CAF: 0.5 ± 0.2L/min), or peak torque (PLA: 144.6 ± 18.6; CAF: 143.9 ± 18.7N·m). CAF decreased rating of perceived exertion (15.9 ± 1.8 vs. 17.0 ± 1.5a.u.) and increased blood lactate concentration (9.0 ± 2.5 vs. 8.3 ± 2.2mmol/L; p < .05) after constant work rate tests compared with PLA. CAF ingestion does not alter V˙O2 kinetics or muscle torque production during 8min of severe-intensity cycling exercise.

Psychophysiological Responses in Soldiers during Close Combat: Implications for Occupational Health and Fitness in Tactical Populations.

This study explores the psychophysiological responses and subjective exertion experiences of soldiers in simulated hand-to-hand combat, aligning these findings with established physiological benchmarks. Active military personnel were monitored for heart rate, blood lactate levels, subjective exertion, cortical arousal, and muscle strength during combat scenarios. The results showed significant increases in heart rate and blood lactate, indicating intense cardiovascular demands and a reliance on anaerobic energy systems. Contrary to these physiological changes, soldiers reported lower levels of exertion, suggesting a possible underestimation of physical effort or individual differences in perception and mental resilience to stress. Notably, a decrease in cortical arousal post-combat was observed, potentially signaling cognitive function deficits in decision-making and information processing in high-stress environments. This decline was more pronounced than typically seen in other high-stress situations, highlighting the unique cognitive demands of hand-to-hand combat. Additionally, an increase in muscle strength was noted, underscoring the physiological adaptations arising from intensive combat training. These findings provide valuable insights into the psychophysiological effects of hand-to-hand combat, emphasizing the complex interplay between physical exertion, cognitive function, and stress response in military contexts. The study underscores the need for comprehensive training strategies that address both physical and psychological aspects to enhance combat readiness and decision-making under stress.

Resistance training in humans and mechanical overload in rodents do not elevate muscle protein lactylation.

Although several reports have hypothesized that exercise may increase skeletal muscle protein lactylation, empirical evidence in humans is lacking. Thus, we adopted a multi-faceted approach to examine if acute and subchronic resistance training (RT) altered skeletal muscle protein lactylation levels. In mice, we also sought to examine if surgical ablation-induced plantaris hypertrophy coincided with increases in muscle protein lactylation. To examine acute responses, participants' blood lactate concentrations were assessed before, during, and after eight sets of an exhaustive lower body RT bout (n = 10 trained college-aged men). Vastus lateralis biopsies were also taken before, 3-h post, and 6-h post-exercise to assess muscle protein lactylation. To identify training responses, another cohort of trained college-aged men (n = 14) partook in 6weeks of lower-body RT (3x/week) and biopsies were obtained before and following the intervention. Five-month-old C57BL/6 mice were subjected to 10 days of plantaris overload (OV, n = 8) or served as age-matched sham surgery controls (Sham, n = 8). Although acute resistance training significantly increased blood lactate responses ∼7.2-fold (p < 0.001), cytoplasmic and nuclear protein lactylation levels were not significantly altered at the post-exercise time points, and no putative lactylation-dependent mRNA was altered following exercise. Six weeks of RT did not alter cytoplasmic protein lactylation (p = 0.800) despite significantly increasing VL muscle size (+3.5%, p = 0.037), and again, no putative lactylation-dependent mRNA was significantly affected by training. Plantaris muscles were larger in OV versus Sham mice (+43.7%, p < 0.001). However, cytoplasmic protein lactylation was similar between groups (p = 0.369), and nuclear protein lactylation was significantly lower in OV versus Sham mice (p < 0.001). The current null findings, along with other recent null findings in the literature, challenge the thesis that lactate has an appreciable role in promoting skeletal muscle hypertrophy.