Peripheral Blood Lactate Research Articles

Glycolytic activity following anti-CD19 CAR-T cell infusion in non-Hodgkin lymphoma.

Energy metabolism of chimeric antigen receptor-T cells (CAR-T) activation in humans remains unexplored. As a glycolytic activity surrogate, we investigated the dynamics of peripheral blood (PB) lactate in the first weeks post-CAR-T infusion. In 17 patients treated with CD28 harbording anti-CD19 CAR-T for relapsed/refractory non-Hodgkin lymphomas, PB lactate levels increased following CAR-T infusion. Elevated lactate levels correlated with longer CAR-T persistence and higher CD8+/CD4+ ratio. Peripheral blood lactate kinetics may reflect immune cells activation and be useful for bedside monitoring.

MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus

Diabetic cardiomyopathy (DCM) is a major contributor to mortality in diabetic patients, characterized by a multifaceted pathogenesis and limited therapeutic options. While lactate, a byproduct of glycolysis, is known to be significantly elevated in type 2 diabetes, its specific role in DCM remains uncertain. This study reveals an abnormal upregulation of monocarboxylate transporter 4 (MCT4) on the plasma membrane of cardiomyocytes in type 2 diabetes, leading to excessive lactate efflux from these cells. The disruption in lactate transport homeostasis perturbs the intracellular lactate-pyruvate balance in cardiomyocytes, resulting in oxidative stress and inflammatory responses that exacerbate myocardial damage. Additionally, our findings suggest increased lactate efflux augments histone H4K12 lactylation in macrophages, facilitating inflammatory infiltration within the microenvironment. In vivo experiments have demonstrated that inhibiting MCT4 effectively alleviates myocardial oxidative stress and pathological damage, reduces inflammatory macrophage infiltration, and enhances cardiac function in type 2 diabetic mice. Furthermore, a clinical prediction model has been established, demonstrating a notable association between peripheral blood lactate levels and diastolic dysfunction in individuals with type 2 diabetes. This underscores the potential of lactate as a prognostic biomarker for DCM. Ultimately, our findings highlight the pivotal involvement of MCT4 in the dysregulation of cardiac energy metabolism and macrophage-mediated inflammation in type 2 diabetes. These insights offer novel perspectives on the pathogenesis of DCM and pave the way for the development of targeted therapeutic strategies against this debilitating condition.

Acute psycho-physiological responses to submaximal constant-load cycling under intermittent hypoxia-hyperoxia vs. hypoxia-normoxia in young males.

Hypoxia and hyperoxia can affect the acute psycho-physiological response to exercise. Recording various perceptual responses to exercise is of particular importance for investigating behavioral changes to physical activity, given that the perception of exercise-induced pain, discomfort or unpleasure, and a low level of exercise enjoyment are commonly associated with a low adherence to physical activity. Therefore, this study aimed to compare the acute perceptual and physiological responses to aerobic exercise under intermittent hypoxia-hyperoxia (IHHT), hypoxia-normoxia (IHT), and sustained normoxia (NOR) in young, recreational active, healthy males. Using a randomized, single-blinded, crossover design, 15 males (age: 24.5 ± 4.2 yrs) performed 40 min of submaximal constant-load cycling (at 60% peak oxygen uptake, 80 rpm) under IHHT (5 × 4 min hypoxia and hyperoxia), IHT (5 × 4 min hypoxia and normoxia), and NOR. Inspiratory fraction of oxygen during hypoxia and hyperoxia was set to 14% and 30%, respectively. Heart rate (HR), total hemoglobin (tHb) and muscle oxygen saturation (SmO2) of the right vastus lateralis muscle were continuously recorded during cycling. Participants' peripheral oxygen saturation (SpO2) and perceptual responses (i.e., perceived motor fatigue, effort perception, perceived physical strain, affective valence, arousal, motivation to exercise, and conflict to continue exercise) were surveyed prior, during (every 4 min), and after cycling. Prior to and after exercise, peripheral blood lactate concentration (BLC) was determined. Exercise enjoyment was ascertained after cycling. For statistical analysis, repeated measures analyses of variance were conducted. No differences in the acute perceptual responses were found between conditions (p ≥ 0.059, ηp 2 ≤ 0.18), while the physiological responses differed. Accordingly, SpO2 was higher during the hyperoxic periods during the IHHT compared to the normoxic periods during the IHT (p < 0.001, ηp 2 = 0.91). Moreover, HR (p = 0.005, ηp 2 = 0.33) and BLC (p = 0.033, ηp 2 = 0.28) were higher during IHT compared to NOR. No differences between conditions were found for changes in tHb (p = 0.684, ηp 2 = 0.03) and SmO2 (p = 0.093, ηp 2 = 0.16). IHT was associated with a higher physiological response and metabolic stress, while IHHT did not lead to an increase in HR and BLC compared to NOR. In addition, compared to IHT, IHHT seems to improve reoxygenation indicated by a higher SpO2 during the hyperoxic periods. However, there were no differences in perceptual responses and ratings of exercise enjoyment between conditions. These results suggest that replacing normoxic by hyperoxic reoxygenation-periods during submaximal constant-load cycling under intermittent hypoxia reduced the exercise-related physiological stress but had no effect on perceptual responses and perceived exercise enjoyment in young recreational active healthy males.

Effects of High-Intensity Interval Training Protocols on Blood Lactate Levels and Cognition in Healthy Adults: Systematic Review and Meta-Regression

Some health benefits from high-intensity interval training (HIIT) are facilitated by peripheral blood lactate levels. However, the lactate response from HIIT is variable and dependent on protocol parameters. We aimed to determine the HIIT protocol parameters that elicited peak lactate levels, and how these levels are associated with post-HIIT cognitive performance. We conducted a systematic review with meta-regression. MEDLINE, Embase, CENTRAL, SPORTDiscus, and CINAHL + were searched from database inception to 8 April, 2022. Peer-reviewed primary research in healthy adults that determined lactate (mmol/L) and cognitive performance after one HIIT session was included. Mixed-effects meta-regressions determined the protocol parameters that elicited peak lactate levels, and linear regressions modelled the relationship between lactate levels and cognitive performance. Study entries (n = 226) involving 2560 participants (mean age 24.1 ± 4.7years) were included in the meta-regression. A low total work-interval volume (~ 5min), recovery intervals that are about five times longer than work intervals, and a medium session volume (~ 15min), elicited peak lactate levels, even when controlling for intensity, fitness (peak oxygen consumption) and blood measurement methods. Lactate levels immediately post-HIIT explained 14-17% of variance in Stroop interference condition at 30min post-HIIT. A HIIT protocol that uses the above parameters (e.g., 8 × 30-s maximal intensity with 90-s recovery) can elicit peak lactate, a molecule that is known to benefit the central nervous system and be involved in exercise training adaptations. This review reports the state of the science in regard to the lactate response following HIIT, which is relevant to those in the sports medicine field designing HIIT training programs. Clinical Trial Registration: PROSPERO (CRD42020204400).

The Influence of Acute Sprint Interval Training on Cognitive Performance of Healthy Younger Adults.

There is considerable evidence showing that an acute bout of physical exercises can improve cognitive performance, but the optimal exercise characteristics (e.g., exercise type and exercise intensity) remain elusive. In this regard, there is a gap in the literature to which extent sprint interval training (SIT) can enhance cognitive performance. Thus, this study aimed to investigate the effect of a time-efficient SIT, termed as “shortened-sprint reduced-exertion high-intensity interval training” (SSREHIT), on cognitive performance. Nineteen healthy adults aged 20–28 years were enrolled and assessed for attentional performance (via the d2 test), working memory performance (via Digit Span Forward/Backward), and peripheral blood lactate concentration immediately before and 10 min after an SSREHIT and a cognitive engagement control condition (i.e., reading). We observed that SSREHIT can enhance specific aspects of attentional performance, as it improved the percent error rate (F%) in the d-2 test (t (18) = −2.249, p = 0.037, d = −0.516), which constitutes a qualitative measure of precision and thoroughness. However, SSREHIT did not change other measures of attentional or working memory performance. In addition, we observed that the exercise-induced increase in the peripheral blood lactate levels correlated with changes in attentional performance, i.e., the total number of responses (GZ) (rm = 0.70, p < 0.001), objective measures of concentration (SKL) (rm = 0.73, p < 0.001), and F% (rm = −0.54, p = 0.015). The present study provides initial evidence that a single bout of SSREHIT can improve specific aspects of attentional performance and conforming evidence for a positive link between cognitive improvements and changes in peripheral blood lactate levels.

Famotidine with Celecoxib Adjuvant Therapy on Hospitalized COVID-19 Patients: A Case Series

BACKGROUND: Up to 80% of SARS-CoV-2 positive patients are asymptomatic and do not appear to progress to COVID-19. SARS-CoV-2 infection is not sufficient for development of COVID-19 disease; this may reflect differences in host inflammatory responses to infection. COX-2 expression is transcriptionally upregulated by SARS nucleocapsid N protein, and COVID-19 is associated with markedly elevated levels of prostaglandin E2 (PGE2). PGE2 modulates a wide variety of innate and adaptive inflammatory responses including mast cell activation. SARS-CoV-2 infection-associated mast cell degranulation may play a role in development of COVID-19. A randomized trial of hospitalized COVID-19 cases has demonstrated that COX-2 protein antagonist celecoxib dampened systemic PGE2 levels, prevented clinical deterioration, and was associated with rapid pulmonary CT-chest improvement. High doses of famotidine, a histamine H2 receptor antagonist/inverse agonist reduces severity of COVID-19 symptoms. We hypothesize that adjuvant therapy with a combination of celecoxib and high dose (HD) famotidine may improve COVID-19 outcomes.METHODS: We report a single institution, consecutive case series of 25 COVID-19 hospitalized patients treated with celecoxib and HD famotidine as adjuvant therapy. Outcome measurements include time to discharge, changes in supplemental oxygen requirements, pulmonary CT-chest findings, and laboratory changes in peripheral blood lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, neutrophil counts, lymphocyte levels, neutrophil/lymphocyte ratio, creatinine, glomerular filtration rate, Interleukin 6 (IL6) and D-dimer concentrations. Nucleocapsid N protein sequence analysis was performed to compare COX-2 promoter activation domains of SARS, SARS-CoV-2, and related Sarbecovirus betacoronaviruses.RESULTS: All 25 patients in the series survived hospitalized COVID-19 without mechanical ventilation or renal replacement therapy (RRT) and were discharged on room air within a median of 3 days (range 1-16 days). Statistically significant improvements from admission to discharge were observed for all aggregated outcome measures. In general, progressive improvement was noted in supplemental oxygen requirements and ground-glass CT findings. Amino acid sequence analysis demonstrated high levels of conservation of N2 protein COX-2 promoter transactivation domains and nuclear localization sequences between SARS, SARS-CoV-2, and closely related Pangolin, Civet cat, and Horseshoe bat coronaviruses, but not MERS or other human or animal Betacoronaviruses.DISCUSSION: In this series, combined treatment with oral celecoxib and HD famotidine in an adjuvant setting was associated with 100% survival and improved radiographic outcomes, as well as statistically significant improvements in clinical, biomarker, and renal function measurements. The 9 patients with extremely high LDH (>365, Wuhan model prediction of 98% mortality) survived and were discharged on room air. Conservation of SARS and SARS-CoV-2 nucleocapsid N protein N2 sequences support that celecoxib treatment may mitigate the effects of direct viral transactivation of COX-2 expression in infected cells. HD famotidine acts to reduce cellular effects of local histamine via H2 receptor antagonism. Acute kidney injury was either prevented or mitigated by treatment; HD famotidine contributes to this effect. In contrast to these findings, previously published COVID-19 clinical intervention studies have not shown consistent laboratory or radiographic improvement. The data support performing randomized placebo-controlled trials to further examine the hypothesis that celecoxib with HD famotidine as adjuvant therapy to standard of care may reverse and prevent clinical deterioration in adult hospitalized COVID-19 patients.

Risk factors associated with gastrointestinal dysfunction in horses undergoing elective procedures under general anaesthesia

Gastrointestinal dysfunction occurs commonly following elective anaesthesia. Identification of risk factors may allow implementation of preventative measures to reduce the prevalence of colic following elective anaesthetic procedures. To examine risk factors associated with gastrointestinal dysfunction or post anaesthetic colic for horses undergoing elective surgical or diagnostic procedures under general anaesthesia. Retrospective case series. Medical records were collected from adult horses undergoing general anaesthesia from 1 January 2008 to 31 December 2010 using a retrospective cohort design. Potential risk factors were examined using univariable logistic regression with a limit of a P<0.25. Through backward elimination, the final multivariate model was created to identify variables significantly associated with gastrointestinal dysfunction. Colic or delayed faecal output was reported in 36 out of 416 (8.7%) horses undergoing general anaesthesia in the study period. In the final multivariable model, horse breed (P = 0.05), intraoperative peripheral blood lactate (P = 0.02), right lateral recumbency during general anaesthesia (P = 0.04), post anaesthetic rectal temperature (P = 0.03) and hours to first passage of faeces (P<0.01) were statistically significant between horses that exhibited colic compared with those that did not. Arabians were more likely to develop colic compared with other horse breeds (4/13, 30.8%). Horses that exhibited gastrointestinal dysfunction passed faeces later than those that did not (7.2 ± 0.8 h and 5.4 ± 0.2 h, respectively). As blood lactate increased at the end of anaesthesia, the odds of colic occurring also increased (odds ratio:1.4, 95% confidence interval: 1.04-1.83, P = 0.02). This study demonstrated the prevalence of colic in horses undergoing elective general anaesthetic procedures in our hospital population. Arabian horses, increasing blood lactate and delayed passage of faeces were significantly associated with an increased risk of gastrointestinal dysfunction.

Peripheral lactate rhythmicity in evening- and morning-fed dairy cows: a chronophysiological lactating model

The objective of the first experiment was to determine effects of feeding time and dietary forage to concentrate ratio on postprandial rhythms of peripheral blood lactate in lactating cows. Four multiparous and four primiparous Holsteins were used in a 4 × 4 Latin square design study with a 2 × 2 factorial arrangement of feeding time and diet type. A higher concentrate (higher concentrate diet (HC), forage to concentrate ratio = 38.5:61.5) or a lower concentrate (lower concentrate diet (LC), forage to concentrate ratio = 50.6:49.4) total mixed ration (TMR) was fed at either 2100 h or 0900 h. The study had four 21-day periods, each with 14-days of adaptation. Blood was sampled every 2 h for two 24-h periods during sampling weeks. Feeding at 2100 h vs. 0900 h increased feed intake within 3-h post-feeding, from 26% to 37% of total daily intake. Feed presentation at 2100 h vs. 0900 h tended to increase daily averages of plasma lactate. The HC diet produced a higher plasma lactate than the LC diet. The plasma lactate increased by about 50% shortly post-feeding in evening-fed cows, but no noticeable changes occurred in morning-fed cows. The objective of the second experiment was to establish postprandial rhythms of peripheral lactate in evening- and morning-fed lactating cows following the 28-day adaptation period. Four multiparous and four primiparous lactating Holstein cows were used in a cross-over design study with two six-week periods, each with four weeks of adaptation. A TMR with 49.8% concentrate was presented at 0900 or 2100 h. The proportion of daily TMR intake consumed within 3-h post-feeding was 55% in cows fed at 2100 h, but only 46% in cows fed at 0900 h. Peripheral lactate exhibited significant daily rhythms. Postprandial responses in peripheral lactate were altered by feeding time. The evening feeding, and not the morning feeding, increased plasma lactate at 4-h and 16-h post-feeding. Feeding time did not affect daily averages of plasma lactate. Results showed that time of feeding (TF) and, thus, time of major eating activity alters postprandial rhythms of feed intake and peripheral lactate. Time of eating, therefore, can affect splanchnic and peripheral lactate metabolism and energy supply in lactating cows.

Effects of added therapy with Chinese herbal medicine Kanli Granule on skeletal muscle dysfunction in patients with chronic heart failure

The pathological changes of skeletal muscle dysfunction in chronic heart failure (CHF) have caused widespread concern, and evaluating the functional properties of medication to improve these pathological changes has become a common area of study for clinicians. To investigate the characteristics of skeletal muscle dysfunction in patients with CHF and the effects of Kanli Granule, a compound traditional Chinese herbal medicine, on the skeletal muscle dysfunction based on Western medical treatment in patients with CHF. All patients with CHF enrolled in this study were outpatients or inpatients in Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from December 2005 to December 2007. The patients were divided into Western medicine group (treatment with Western medicine) and Chinese herbs group (treatment with Kanli Granule based on Western medicine) based on their preference. The treatment course lasted for 12 weeks. The grip strength, grasp times, rate of perceived exertion (RPE), estimated heart rate, peripheral blood lactate levels and lactate dehydrogenase (LDH) isoenzyme activity in patients were measured. A total of 92 patients were recruited and 12 patients withdrew from the Western medicine group, therefore a total of 80 patients were included in the follow-up study. There were 46 cases in the Chinese herbs group and 34 cases in the Western medicine group. After treatment, grip strength and grasp times increased significantly compared with before treatment. RPE score and estimated heart rate significantly decreased in the two groups, showing greater changes in the Chinese herbs group than the Western medicine group (P<0.01). Peripheral blood lactate levels of the CHF patients in a resting state decreased, and the Chinese herbs group displayed a greater decrease than the Western medicine group (P<0.05); lactate levels 3 min after exercise decreased after treatment in both treatment groups, but no significant difference was found compared with before treatment; LDH1 levels in the two treatment groups were decreased compared with before treatment but showed no statistically significant changes; LDH5 levels in the two treatment groups increased after treatment, and an obvious difference was found in the Chinese herbs group (P<0.01). Treatment with the addition of Kanli Granule can significantly improve the function of skeletal muscle in patients with CHF by improving skeletal muscle energy metabolism.

The effects of progressive exercise on cardiovascular function in elite athletes: Focus on oxidative stress

Some side-effects of excessive physical training are ascribed to reactive oxygen species production. In this work we investigated the effects of progressively imposed maximal physical effort (levels I to V), using progressive maximal exercise test, on peripheral blood lactate, NO (through NO2-), superoxide anion (O2-) and methemoglobin (MetHb) in a group of 19 elite soccer players. Blood lactate (mmol/L) was increased (4.55, level V vs. resting level, 1.95). The basal production of NO2- was in the direct relation with O2 consumption. Significant increase (p<0.05) in O2- values at effort level I (4.18) as compared to the resting value (4.01), and the significant increase (p<0.01 or p<0.05) in the MetHb (%) was found between II (18.79) and III (19.63) or between II and IV (19.24) effort levels, respectively. The regression lines of NO2- and O2- crossed at the level of the respiratory compensation point (RC), suggesting that RC could be of a crucial importance not only in the anaerobic and aerobic metabolism but in mechanisms of signal transductions as well. The results could be of the theoretical interest and also useful in designing an athlete training strategy.

Changes of blood lactate levels after repetitive transcranial magnetic stimulation

The objective was to study whether repetitive transcranial magnetic stimulation (rTMS) of the motor cortex could induce modification of peripheral blood lactate values. Nineteen young healthy volunteers were included; during the study, all subjects were at rest, sitting on a comfortable armchair. The muscular activation was evaluated by continuous electromyographic record. TMS was performed by using a circular coil at the vertex. Resting motor threshold (rMT) was defined as the lowest TMS intensity able to induce motor responses of an amplitude >50μV in the relaxed contralateral target muscle in approximately 50% of 20 consecutive stimuli. Venous blood lactate values were measured before, immediately after and 10min after a single session of low frequencies (1Hz for 15min) rTMS (LF rTMS) or high frequency (20Hz for 15min) rTMS (HF rTMS). As expected, LF rTMS induced a decrease of motor cortex excitability, whereas HF rTMS evoked an increase of motor cortex excitability. However, in the present investigation we observed that both conditions are associated to a significant increase of blood lactate. Since in our experimental conditions we can exclude a muscular production of lactate, the significant increment of peripheral blood lactate values, observed 10min after the end of the rTMS session, is probably due to the crossing by brain-produced lactate of the blood–brain barrier.

Acute Moderate Sleep Deprivation Attenuates Physiological and Psychological Function at Rest and During Exercise

Previous research indicates that total sleep deprivation can elicit a number of physiological and psychological deficits including mood disturbance and autonomic imbalance. Little is known regarding the effects of a single night of moderate sleep loss, a much more common occurrence. PURPOSE: To determine the effects of acute moderate sleep deprivation (AMSD) on resting heart rate variability (HRV) and mood, as well as heart rate (HR), oxygen consumption (VO2), peripheral blood lactate and ratings of perceived exertion (RPE) during steady state exercise. METHODS: Thirteen healthy male subjects (age: 20+0.25 years; peak VO2:=52.0+ 2.7 ml/kg/min) gave informed, written consent and underwent initial testing to determine peak VO2 on a calibrated cycle ergometer. Following the AMSD (2-4 hours of sleep) or rested (8-10 hours of sleep) state, submaximal exercise tests were completed. Prior to sub-maximal tests, subjects completed the profile of mood state (POMS) inventory and resting heart rate variability (HRV) was recorded from a lead II ECG for 30 minutes. Submaximal exercise tests were completed at 40% (low workload) and 70% (high workload) of peak VO2. Heart rate, VO2, RPE and blood lactate was recorded during steady state levels (4-6 minutes) at each stage. Data were statistically analyzed using paired t-test with significance set at p < 0.05. RESULTS: Following AMSD, baseline HRV was significantly reduced (118+10.2 vs. 103+8.7 ms). Significantly elevated POMS scores of tension, anger, and fatigue contributed to a significant increase in the total mood disturbance score (2.5+5.6 vs. 24.2+7.8). Exercise HR was significantly higher during both the low (122+2.8 vs. 132+2.5 bpm) and high (161+2.9 vs. 171+2.5 bpm) workloads following AMSD as compared to the rested state. Although blood lactate was significantly greater during the high workload following AMSD (7.5+0.7 vs. 9.4+0.7mmol/L) no significant differences were found between VO2, RPE, and blood lactate at any other workload following AMSD. CONCLUSION: These data indicate that AMSD elicits autonomic imbalance and impairments in both physiological and psychological function at rest and during exercise.

Blood lactate changes in men during graded workloads at normal atmospheric pressure (100 kPa) and under simulated caisson conditions (400 kPa).

A hyperbaric environment may influence lactate metabolism due to hyperoxia affecting biochemical pathways. The purpose of our study was to determine the blood lactate levels occurring at high workloads in a sample of professional divers under simulated caisson conditions. The ambient air pressure was equivalent to a diving depth of 30 m of seawater (400 kPa). A total of 23 healthy male subjects performed graded bicycle exercise in a dry hyperbaric chamber up to a maximum of 3.5 W kg(-1) body weight at normal (100 kPa) and elevated ambient air pressure (400 kPa). The blood lactate level and the heart rate were measured. In comparison with control conditions, the heart rate and the peripheral blood lactate level were significantly lower at depth for all workloads. The differences between the normobaric and hyperbaric lactate values may be explained by an overall improvement in lactate metabolism at elevated ambient pressure, especially in the working muscles and the organs responsible for the lactate reduction, i.e., the liver. The reduced heart rate may be an effect of the improved tissue oxygen supply at depth.

Resting peripheral blood lactate elevation in survivors of prehospital cardiac arrest: Correlation with hemodynamic, electrophysiologic and oxyhemoglobin dissociation indexes

Thirteen patients who were survivors of sudden unexpected cardiac arrest in the community were followed up for up to 3 years. All showed an anomalous relation between erythrocyte levels of oxygen dissociation (P 50) and 2,3-diphosphoglyceric acid (2,3-DPG). This could not be explained by hemoglobinopathy, carbon monoxide or methemoglobinemias. Because lactate accumulation in red blood cells may alter oxygen dissociation, whole blood and red blood cell lactate levels were measured. An average of 4.4 measurements per patient were obtained over a mean time of 5.6 months of the post-hospital phase of the follow-up period, which had a total mean duration of 22 months. The patients did not have overt congestive heart failure and were not acidotic (mean venous pH = 7.35). Lactate levels were elevated (mean = 15.1 mg/100 ml ± 0.8 mg/100 [standard error of the mean], compared with normal values of 7.6 mg/100 ml ± 1.4 mg/100 ml; P < 0.01). When lactate was plotted against red blood cell 2,3-diphosphoglycerate, a positive curvilinear relation was found ( r 2 = 0.12, P < 0.05). The production of lactate in chronic ischemia may increase red blood cell 2,3-diphosphoglycerate through glycolysis. The expected effect on oxygen dissociation of this increase in 2,3-diphosphoglycerate is offset by a counterbalancing leftward shift of the oxyhemoglobin dissociation curve by an increase in red blood cell lactic acid. When lactate was compared with left ventricular ejection fraction, there was a significant negative correlation ( r = 0.86, P < 0.01). Serial 24 hour ambulatory electrocardiograms (mean 4 per patient) were analyzed for changes in quantity and severity of ventricular arrhythmia at the time of lactate determinations. Six patients had lactate level variation of more than 30 percent, and five of these six patients had an increase in quantity and severity of ventricular ectopic activity when their lactate levels were in the higher range. We conclude that elevated resting lactate levels correlate with impaired ventricular function, and fluctuations in a given patient may identify changes in clinical and electrophysiologic status.