Arteriovenous Lactate Difference Research Articles

A systematic meta-analysis of oxygen-to-glucose and oxygen-to-carbohydrate ratios in the resting human brain.

Glucose is the predominant fuel supporting brain function. If the brain’s entire glucose supply is consumed by oxidative phosphorylation, the molar ratio of oxygen to glucose consumption (OGI) is equal to 6. An OGI of less than 6 is evidence of non-oxidative glucose metabolism. Several studies have reported that the OGI in the resting human brain is less than 6.0, but the exact value remains uncertain. Additionally, it is not clear if lactate efflux accounts for the difference between OGI and its theoretical value of 6.0. To address these issues, we conducted a meta-analysis of OGI and oxygen-to-carbohydrate (glucose + 0.5*lactate; OCI) ratios in healthy young and middle-aged adults. We identified 47 studies that measured at least one of these ratios using arterio-venous differences of glucose, lactate, and oxygen. Using a Bayesian random effects model, the population median OGI was 5.46 95% credible interval (5.25–5.66), indicating that approximately 9% of the brain’s glucose metabolism is non-oxidative. The population median OCI was 5.60 (5.36–5.84), suggesting that lactate efflux does not account for all non-oxidative glucose consumption. Significant heterogeneity across studies was observed, which implies that further work is needed to characterize how demographic and methodological factors influence measured cerebral metabolic ratios.

Lactate supplementation in severe traumatic brain injured adults by primed constant infusion of sodium L-lactate.

Carbohydrate fuel augmentation following traumatic brain injury may be a viable treatment to improve recovery when cerebral oxidative metabolism of glucose is depressed. We performed a primed constant sodium L-lactate infusion in 11 moderate to severely brain injured adults. Blood was collected before and periodically during the infusion study. We quantified global cerebral uptake of glucose and lactate and other systemic metabolites associated with energy metabolism. Our hypothesis was that cerebral lactate uptake, as measured by the arteriovenous difference of lactate (AVDlac), would increase in severely injured TBI patients in the neurocritical care unit. Infusion of sodium L-lactate changed net cerebral lactate release, where the arteriovenous difference of lactate is negative, to net cerebral lactate uptake. Results from a mixed effects model of AVDlac with the fixed effects of infusion time, arterial lactate concentration, arterial glucose concentration and arteriovenous difference of glucose shows that doubling arterial lactate concentration (from .92 to 1.84 mM) results in an increase in AVDlac from -.078 mM to .090 mM. We did not detect changes in systemic glucose during the course of the infusion study and observed significant changes in alanine (30% [20 39]), glutamine (34% [24 43]), acetate (87% [60 113]), valine (40% [28 51]), and leucine (24% [16 32]) from baseline levels. Further studies are required to establish the impact of lactate supplementation on cerebral and systemic flux of lactate, on gluconeogenesis, and on the impact on cerebral energetics following injury. © 2017 Wiley Periodicals, Inc.

Arteriovenous differences of lactate and pyruvate across healthy and diseased human lung.

In 14 patients with pulmonary tuberculosis or carcinoma, the differences between arterial and mixed venous blood concentrations of lactate and pyruvate were small, random in direction, and indistinguishable from those obtained in 8 subjects with normal lungs. In contrast, 4 patients with particularly widespread, active tuberculosis had arteriovenous differences which suggested that the lungs added lactate to the blood. To examine this possibility, local differences across diseased lobes were measured directly in 16 patients undergoing thoracotomy for tuberculosis or carcinoma. In all 16, the local differences indicated a production of lactate by the diseased lobe or lobule. In 8 of the patients, arteriovenous differences of lactate were measured simultaneously, and in 6 of the 8, the differences were smaller than those measured locally. These data suggested that the diluting effect of blood perfusing normal regions might have accounted for earlier failures to find consistent arteriovenous lactate differen...

Lactate Uptake by the Injured Human Brain: Evidence from an Arteriovenous Gradient and Cerebral Microdialysis Study

Lactate has been regarded as a waste product of anaerobic metabolism of glucose. Evidence also suggests, however, that the brain may use lactate as an alternative fuel. Our aim was to determine the extent of lactate uptake from the circulation into the brain after traumatic brain injury (TBI) and to compare it with levels of lactate in the brain extracellular fluid. We recruited 19 patients with diffuse TBI, monitored with cerebral microdialysis and jugular bulb catheters. Serial arteriovenous (AV) concentration differences of glucose and lactate were calculated from arterial and jugular blood samples, providing a measure of net uptake or export by the brain. Microdialysis was used to measure brain extracellular glucose and lactate. In 17/19 patients studied for 5 days post-injury, there were periods of net lactate uptake into the brain, most frequently on day 3 after injury. Brain microdialysate lactate had a median (interquartile range [IQR]) concentration of 2.5 (1.5-3.2) mmol/L during lactate uptake and 2.2 (1.7-3.0) mmol/L during lactate export. Lactate uptake into the brain occurred at a median (IQR) arterial lactate concentration of 1.6 (1.0-2.2) mmol/L. Lactate uptake was associated with significantly higher AV difference in glucose values with a median (IQR) of 0.4 (0.03-0.7) mmol/L during uptake and 0.1 (-0.2-0.3) mmol/L during lactate export (Mann-Whitney U p=0.003). Despite relatively high brain lactate compared with arterial lactate concentrations, the brain appears to up-regulate lactate transport into the brain after TBI. This may serve to satisfy greater demands for energy substrate from the brain after TBI.

Atrial supply–demand balance in healthy adult pigs: coronary blood flow, oxygen extraction, and lactate production during acute atrial fibrillation

Little is known about how atrial oxygen supply responds to increased demand, and under which conditions it falls short (supply-demand mismatch). Here, we have investigated the vasodilator response, oxygen extraction, and lactate production of the left atrium (LA) and left ventricle (LV) in response to atrial pacing and atrial fibrillation (AF). Series A (n = 9 Dutch landrace pigs) was instrumented to measure LA and LV vascular conductance in branches of the circumflex artery. Coronary conductance reserve (CCR) was calculated as the ratio between conductance during adenosine infusion and baseline. Series B (n = 7) was instrumented with sampling catheters in LA and LV veins for determination of blood gases and lactate levels. LA CCR (1.76 ± 0.14) was significantly lower than LV CCR (3.16 ± 0.27, P = 0.002). However, basal oxygen extraction was lower in LA (27 ± 3%) than that in the LV (58 ± 6%, P = 0.0006), indicating a larger extraction reserve in the LA than that in the LV (4.68 ± 0.84 vs. 1.88 ± 0.26, P = 0.01). Atrial pacing caused an increase in LA conductance (Series A) and oxygen extraction (Series B). AF increased LA vascular conductance to 177 ± 14% at 1 min, 168 ± 14 at 5 min, and 164 ± 31% at 10 min of AF (P < 0.05 vs. baseline). Atrial oxygen extraction also increased from 26 ± 3% at baseline to 63 ± 5% (P < 0.01) at 5 min and 60 ± 11% (P < 0.01) at 10 min of AF. Arterio-venous lactate difference increased significantly (P = 0.02) during AF. In healthy pigs, the LA has a lower CCR, but a higher extraction reserve compared with the LV. Although both reserves were recruited during AF, atrial lactate production increased significantly.

Lactate metabolism during exercise in patients with mitochondrial myopathy

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.

Haemodynamic and metabolic effects of low daily dose sulphonylureas in diabetic dog hearts.

The effects of glibenclamide (GB, CAS 10238-21-8) and those of the latest low daily dose sulphonylurea compound, glimepiride (GM, CAS 93479-97-1) on myocardial haemodynamics and pyruvate-lactate metabolism of healthy and alloxan-diabetic dogs (n = 6 in six groups) were compared. Mean arterial blood pressure, heart rate, blood flow of the left anterior descending coronary artery, myocardial contractile force, the rate of change of myocardial contraction and relaxation were measured and arterial (a. carotis communis) and venous (sinus coronarius) pyruvate and lactate concentrations were determined during i.v. administration of the drugs (0, 0.4, 2, 5, and 8 mumol/kg). Coronary conductivity, pressure-rate product and pyruvate-lactate extraction rates were calculated. Glimepiride reduced the heart rate in diabetic animals. Both compounds decreased myocardial contractile force, coronary blood flow and conductivity and the rate of change of myocardial contraction. However, alterations in blood pressure, pressure-rate product, the rate of change of myocardial relaxation and arterio-venous lactate difference elicited by glibenclamide proved to be more expressed than those by glimepiride. According to the results, glibenclamide and especially glimepiride do not enhance the disturbances of the cardiovascular system in diabetes. By this reason, considering its very low daily dose and favourable haemodynamic effects, glimepiride could preferably be recommended for the treatment of type 2 diabetics with coronary heart disease.

Adenosine in cold blood cardioplegia - a placebo-controlled study

OBJECTIVE Adenosine as an additive in blood cardioplegia is cardioprotective in animal studies, but its clinical role in myocardial protection remains controversial. The aim of this study was to investigate whether the addition of adenosine in continuous cold blood cardioplegia would enhance myocardial protection. METHODS In a prospective double-blind study comparing adenosine 400 μmol l(-1) to placebo in continuous cold blood cardioplegia, 80 patients undergoing isolated aortic valve replacement were randomized into four groups: antegrade cardioplegia with adenosine (n = 19), antegrade cardioplegia with placebo (n = 21), retrograde cardioplegia with adenosine (n = 21) and retrograde cardioplegia with placebo (n = 19). Myocardial arteriovenous differences in oxygen and lactate were measured before, during and after aortic occlusion. Myocardial concentrations of adenine nucleotides and lactate were determined from left ventricular biopsies obtained before aortic occlusion, after bolus cardioplegia, at 60 min of aortic occlusion and at 20 min after aortic occlusion. Plasma creatine kinase (CK-MB) and troponin T were measured at 1, 3, 6, 9, 12 and 24 h after aortic occlusion. Haemodynamic profiles were obtained before surgery and 1, 8 and 24 h after cardiopulmonary bypass. Repeated-measures analysis of variance was used for significance testing. RESULTS Adenosine had no effects on myocardial metabolism of oxygen, lactate and adenine nucleotides, postoperative enzyme release or haemodynamic performance. When compared with the antegrade groups, the retrograde groups showed higher myocardial oxygen uptake (17.3 ± 11.4 versus 2.5 ± 3.6 ml l(-1) at 60 min of aortic occlusion, P < 0.001) and lactate accumulation (43.1 ± 20.7 versus 36.3 ± 23.0 µmol g(-1) at 60 min of aortic occlusion, P = 0.052) in the myocardium during aortic occlusion, and lower postoperative left ventricular stroke work index (27.2 ± 8.4 versus 30.1 ± 7.9 g m m(-2), P = 0.034). CONCLUSIONS Adenosine 400 μmol l(-1) in cold blood cardioplegia showed no cardioprotective effects on the parameters studied. Myocardial ischaemia was more pronounced in patients receiving retrograde cardioplegia.

Cerebral glucose and lactate consumption during cerebral activation by physical activity in humans

At rest, the brain takes up oxygen and carbohydrate at an ~6:1 ratio. Exercise increases systemic lactate availability reducing this to as little as 1.7:1 despite a ~20% increase in cerebral metabolic rate for oxygen (CMRo₂), thus indicating a disproportionate increase of carbohydrate metabolism. Underlining mechanisms and metabolic fate for the augmented lactate uptake are unknown. This meta-analysis examines whether adrenergic activation explains the increased lactate uptake, cerebral lactate release following cerebral activation compensates for the extra carbohydrate uptake during exercise, and cerebral lactate uptake spares glucose as fuel. Ten studies (n=96) measuring arteriovenous differences for lactate, glucose, and oxygen and cerebral blood flow were included. Cerebral lactate uptake increased during brain activation by whole-body exercise compared to the resting state. Unlike glucose, lactate uptake is proportional to its arterial concentration but is unaffected by sympathetic activity. Following exercise, significant cerebral lactate released as arterial lactate levels decreased, which may balance the surplus lactate uptake in the brain during physical activity in the long term. Finally, cerebral glucose uptake was reduced by ~25% in relation to CMRo₂ when cerebral lactate uptake increased, suggesting, in part, preferential lactate consumption during activation. This meta-analysis favors the notion that cerebral lactate uptake is mainly passively governed by its availability, but when lactate is available, lactate supplements glucose and supports an increase in cerebral energy metabolism in an activity-dependent manner.

Effect of Equiosmolar Solutions of Mannitol versus Hypertonic Saline on Intraoperative Brain Relaxation and Electrolyte Balance

The purpose of the study was to compare the effect of equiosmolar solutions of mannitol and hypertonic saline (HS) on brain relaxation and electrolyte balance. After institutional review board approval and informed consent, patients with American Society of Anesthesiologists physical status II-IV, scheduled to undergo craniotomy for various brain pathologies, were enrolled into this prospective, randomized, double-blind study. Patients received 5 ml/kg 20% mannitol (n = 20) or 3% HS (n = 20). Partial pressure of carbon dioxide in arterial blood was maintained at 35-40 mmHg, and central venous pressure was maintained at 5 mmHg or greater. Hemodynamic variables, fluid balance, blood gases, electrolytes, lactate, and osmolality (blood, cerebrospinal fluid, urine) were measured at 0, 15, 30, and 60 min and 6 h after infusion; arteriovenous difference of oxygen, glucose, and lactate were calculated. The surgeon assessed brain relaxation on a four-point scale (1 = relaxed, 2 = satisfactory, 3 = firm, 4 = bulging). Appropriate statistical tests were used for comparison; P < 0.05 was considered significant. There was no difference in brain relaxation (mannitol = 2, HS = 2 points; P = 0.8) or cerebral arteriovenous oxygen and lactate difference between HS and mannitol groups. Urine output with mannitol was higher than with HS (P < 0.03) and was associated with higher blood lactate over time (P < 0.001, compared with HS). Cerebrospinal fluid osmolality increased at 6 h in both groups (P < 0.05, compared with baseline). HS caused an increase in sodium in cerebrospinal fluid over time (P < 0.001, compared with mannitol). Mannitol and HS cause an increase in cerebrospinal fluid osmolality, and are associated with similar brain relaxation scores and arteriovenous oxygen and lactate difference during craniotomy.

Cerebral Arterio-venous pCO2 Difference, Estimated Respiratory Quotient, and Early Posttraumatic Outcome: Comparison With Arterio-venous Lactate and Oxygen Differences

Arterio-venous pCO2 difference (AVDpCO2) and estimated respiratory quotient, the ratio between AVDpCO2 and arterio-venous O2 difference, may be potentially useful estimators of irreversible posttraumatic global cerebral ischemia. Our aim was to evaluate their relevance, along with arterio-venous lactate difference (AVDL) and lactate oxygen index (LOI), in early outcome prediction. The retrospective study involved 55 patients with severe head injury, admitted consecutively in a multidisciplinary intensive care unit of a general hospital. A retrograde jugular catheter was placed as soon as possible, allowing for 324 simultaneous arterio-jugular samples to be taken throughout the first 48-hour postinjury. Early brain death (within 48 h) was assumed to be due to early global ischemia. A multivariate model including clinical and radiologic descriptors and jugular bulb variables showed that a widening of AVDL and LOI was associated with early brain death. Whereas in the patients who died, a progressive worsening of AVDpCO2 and estimated respiratory quotient, associated with corresponding changes in AVDL and LOI were observed, in patients who survived the widening of AVDpCO2 normalized along with that of arterio-venous O2 difference. These findings suggest that the isolated measurement of widening AVDpCO2 is not specific for global cerebral ischemia, but its observation over time could be potentially more useful.

Release of cardiac bio-markers during high mechanical index contrast-enhanced echocardiography in humans

Recent experimental data have shown that the combined exposure of rodent hearts to high acoustic pressure and ultrasound contrast agents can induce vascular injury and cell damage. The aim of the present work was to test whether similar effects can be observed in humans. Twenty patients underwent simultaneous arterial and coronary sinus blood sampling during contrast-enhanced echocardiography using Perfluorocarbon-enhanced Sonicated Dextrose Albumin. Control subjects were compared to groups of patients exposed to either high mechanical index (MI = 1.5) triggered second harmonic (1.3-2.6 MHz) imaging or low mechanical index (MI = 0.2) real-time power modulation imaging for 15 min. No significant changes arterio-venous differences in lactate, total creatine kinase (CK) and myoglobin occurred over time in the three groups. Similarly, the arterio-venous difference in CK-MB and troponin I remained stable over time in control and low-MI patients. By contrast, these two parameters progressively increased over time in the high-MI group (P < 0.05 vs. baseline and vs. controls). Our data suggest that high-MI contrast-enhanced echocardiography can cause subclinical release of cardiac bio-markers in humans, while low-MI real-time imaging appears to be safer.

The brain does not take up lactate during exercise in hypoxia

Cerebral function depends on continuous oxygen delivery, but whether the brain has a potential for anaerobic metabolism is not known. The brain has a small net lactate production at rest while during exercise it takes up lactate in proportion to the arterial concentration. This study evaluated whether cerebral oxygen availability affects the brains lactate metabolism as arterio-venous lactate differences (a-v diff) in 16 subjects during 3 cycling trials: 20 min of submaximal exercise at a normal inspired oxygen fraction (FIO2 0.21); at a FIO2 of 0.10; and 3) during exercise to exhaustion (FIO2 0.21). Blood was sampled from the brachial artery and a catheter placed at the jugular bulb, while cerebral blood flow was appreciated with transcranial ultrasound Doppler. At rest and during submaximal exercise at FIO2 0.21, the mean cerebral a-v diff was −0.1 ± 0.1 (SD) mM. Maximal exercise increased arterial lactate to 10.5 ± 2.1 mM with a lactate a-v diff of 0.7 ± 0.4 mM. However, exercise at a FIO2 of 0.10 reduced oxygen availability from 476 ± 80 to 350 ± 41 μmol 100 g−1 min−1 and the arterial lactate concentration increased to 10.1 ± 4.0 mM, but no a-v diff for lactate was observed. While net cerebral carbohydrate [glucose + ½lactate] turn-over was preserved, the cerebral oxygen metabolic rate for oxygen decreased by 15 ± 10 %. This indicates that exercise in hypoxia provokes the brain to provide energy by anaerobic metabolism.

Brain oxygen utilization is unchanged by hypoglycemia in normal humans: lactate, alanine, and leucine uptake are not sufficient to offset energy deficit

During hypoglycemia, substrates other than glucose have been suggested to serve as alternate neural fuels. We evaluated brain uptake of endogenously produced lactate, alanine, and leucine at euglycemia and during insulin-induced hypoglycemia in 17 normal subjects. Cross-brain arteriovenous differences for plasma glucose, lactate, alanine, leucine, and oxygen content were quantitated. Cerebral blood flow (CBF) was measured by Fick methodology using N(2)O as the dilution indicator gas. Substrate uptake was measured as the product of CBF and the arteriovenous concentration difference. As arterial glucose concentration fell, cerebral oxygen utilization and CBF remained unchanged. Brain glucose uptake (BGU) decreased from 36.3+/-2.6 to 26.6+/-2.1 micromol.100 g of brain(-1).min(-1) (P<0.001), equivalent to a drop in ATP of 291 micromol.100 g(-1).min(-1). Arterial lactate rose (P<0.001), whereas arterial alanine and leucine fell (P<0.009 and P<0.001, respectively). Brain lactate uptake (BLU) increased from a net release of -1.8+/- 0.6 to a net uptake of 2.5+/-1.2 micromol.100 g(-1).min(-1) (P<0.001), equivalent to an increase in ATP of 74 micromol.100 g(-1).min(-1). Brain leucine uptake decreased from 7.1+/-1.2 to 2.5 +/- 0.5 micromol.100 g(-1).min(-1) (P<0.001), and brain alanine uptake trended downward (P<0.08). We conclude that the ATP generated from the physiological increase in BLU during hypoglycemia accounts for no more than 25% of the brain glucose energy deficit.

Mixed Venous-Arterial CO2 Tension Gradient after Cardiopulmonary Bypass

Significant venous hypercarbia has been reported in septic shock and circulatory failure. Cardiopulmonary bypass also impairs systemic and pulmonary blood perfusion. The objective of this study was to determine the clinical significance of the increased venous-arterial CO2 tension gradient resulting from venous hypercarbia after cardiopulmonary bypass. On arrival in the intensive care unit, venous and arterial CO2 tensions were measured in the radial and pulmonary arteries in 140 consecutive patients who had undergone coronary (n = 79), valve (n = 34), aortic (n = 20), and other (n = 7) surgery under cardiopulmonary bypass. The mean venous-arterial CO2 tension gradient was 5.0 +/- 3.3 mm Hg (range, 7.7 to 15.7 mm Hg). By linear regression analysis, the factors that significantly correlated with venous-arterial CO2 tension gradient were bypass duration, aortic crossclamp time, initial arterial lactate level, transpulmonary arteriovenous lactate difference, arterial bicarbonate level, base excess, cardiac index, mixed venous O2 saturation, O2 delivery, O2 consumption, and the peak value of creatine kinase. The venous-arterial CO2 tension gradient may reflect impaired perfusion and anaerobic metabolism induced by cardiopulmonary bypass and could be a simple and useful indicator for patient management after surgery under cardiopulmonary bypass.

Significance of the initial arterial lactate level and transpulmonary arteriovenous lactate difference after open-heart surgery.

This study was conducted to determine the clinical significance of the initial lactate level and its transpulmonary difference after open-heart surgery in adult patients. The initial postoperative lactate levels were obtained from both radial and pulmonary arteries (La, Lv) in 65 consecutive patients undergoing coronary (n = 46), valve (n = 8), and aortic (n = 11) surgery. We analyzed the relationships between the perioperative factors and La and transpulmonary arteriovenous lactate difference (%La-v = 100(La - Lv)/Lv). La and % La-v were not correlated with the preoperative factors of age, pulmonary function, or emergency surgery. La significantly correlated with the cardiopulmonary bypass time, initial arterial pH, initial PaO2/FiO2, SvO2, O2 consumption, O2 extraction rate, and the peak value of creatine phosphokinase. The %La-v significantly correlated with the aortic cross-clamp time, the lowest rectal temperature, the duration of intubation, and PaO2/FiO2 after extubation. La may be an indicator of the invasiveness of the surgery, while %La-v may be a predictor of postoperative pulmonary function. Both La and %La-v, as an initial value in the intensive care unit, may play an important role in planning the postoperative management of patients undergoing open-heart surgery.

Detection of early ischemia in severe head injury by means of arteriovenous lactate differences and jugular bulb oxygen saturation. Relationship with CPP, severity indexes and outcome. Preliminary analysis.

Early ischemia may be highly relevant in patients with severe head injuries. The aims of the study were: 1) to define if abnormal arteriovenous lactate difference (AVDL) and jugular bulb oxygen saturation (SjO2) are found in the early 24 hrs post injury; 2) to compare if abnormalities of SjO2 and of AVDL were associated with a specific typology of severity indexes and outcome; 3) to detect any association between abnormal AVDL and SjO2 with levels of cerebral perfusion pressure (CPP). The study involved 29 patients, with CPP, AVDL and SjO2 measured within 24 hours post-injury. 1) Abnormal AVDL was found in 21% while abnormal SjO2 was detected in 38% of the patients; 2) abnormal AVDL was associated with cases of most severe injury; 3) CPP level below 60 mmHg was associated with abnormal AVDL and SjO2. Low CPP appeared to be the most likely measurable cause of early ischemia. Abnormalities of AVDL appeared to be more sensitive, than SjO2, with regard to detection of the most severe cases.

Enhanced pyruvate dehydrogenase activity does not affect muscle O2 uptake at onset of intense exercise in humans.

It has been proposed that the activation state of pyruvate dehydrogenase (PDH) may influence the rate of skeletal muscle O2 uptake during the initial phase of exercise; however, this has not been directly tested in humans. To remedy this, we used dichloroacetate (DCA) infusion to increase the active form of PDH (PDH(a)) and, subsequently, measured leg O2 uptake and markers of anaerobic ATP provision during conditions of intense dynamic exercise, when the rate of muscle O2 uptake would be very high. Six subjects performed brief bouts of one-legged knee-extensor exercise at approximately 110% of thigh peak O2 uptake (65.3 +/- 3.7 W) on several occasions: under noninfused control (Con) and DCA-supplemented conditions. Needle biopsy samples from the vastus lateralis muscle were obtained at rest and after 5 s, 15 s, and 3 min of exercise during both experimental conditions. In addition, thigh blood flow and femoral arteriovenous differences for O2 and lactate were measured repeatedly during the 3-min work bouts (Con and DCA) to calculate thigh O2 uptake and lactate release. After DCA administration, PDH(a) was four- to eightfold higher (P < 0.05) than Con at rest, and PDH(a) remained approximately 130% and 100% higher (P < 0.05) after 5 and 15 s of exercise, respectively. There was no difference between trials after 3 min. Despite the marked difference in PDH(a) between trials at rest and during the initial phase of exercise, thigh O2 uptake was the same. In addition, muscle phosphocreatine utilization and lactate production were similar after 5 s, 15 s, and 3 min of exercise in DCA and Con. The present findings demonstrate that increasing PDH(a) does not alter muscle O2 uptake and anaerobic ATP provision during the initial phase of intense dynamic knee-extensor exercise in humans.

Hypothermic cardiopulmonary bypass alters oxygen/glucose uptake in the pediatric brain

Objectives: Neurologic morbidity related to cardiac surgery has been recognized as a major morbidity. A variety of causes related to cardiopulmonary bypass, including microemboli, nonpulsatile flow, hemodilution, and inflammatory mediation, have been proposed. Because oxygen and glucose are the predominant metabolic substrates for the brain, we sought to examine the uptake of these substrates by the pediatric brain during hypothermic cardiopulmonary bypass. Methods: Eleven children (median age 5 months, range 1 day-17 years) undergoing a variety of cardiac surgical procedures with the use of hypothermic cardiopulmonary bypass were studied. Cerebral arteriovenous differences for oxygen, glucose, and lactate were obtained before, during, and after bypass. On the basis of the predictable stoichiometric relationship for the oxidation of glucose, the relationship of substrate uptake was expressed as the oxygen/glucose index. Oxygen/glucose index (%) = (arteriovenous oxygen difference [μmol/mL]/arteriovenous glucose difference [μmol/mL] × 6) × 100 Results: All children survived with no obvious neurologic sequelae. During cooling on cardiopulmonary bypass, the oxygen/glucose indexes fell significantly from prebypass values (53% ± 19% at 28°C and 54% ± 25% at 24°C vs 117% ± 70%; P <.05, analysis of variance). This decline resulted from decreased oxygen uptake with stable glucose uptake (P <.05). Although oxygen and glucose uptake both increased with rewarming, the net effect was only a slight increase in oxygen/glucose index (62% ± 16%). Postbypass oxygen/glucose index exceeded prebypass values (149% ± 83%). Conclusions: Hypothermic cardiopulmonary bypass alters the relationship between oxygen and glucose uptake in the pediatric brain. The relationship of these findings to bypass-related neurologic morbidity remains to be explored. (J Thorac Cardiovasc Surg 2001;121:366-73)

Captopril-induced glutamate release at the start of reperfusion after cold cardioplegic storage of pig hearts

Objective: We sought to evaluate the effects of captopril on glucose-related metabolism during hypothermic cardioplegic storage and subsequent reperfusion. Methods: We compared hearts from control pigs with hearts from pigs treated with increasing oral doses of captopril for 3 weeks (12.5-150 mg daily), an intravenous bolus (25 mg) before operation, and captopril-containing cardioplegic solution (1 mg/L). The hearts were excised after infusion of cold crystalloid cardioplegic solution and stored in saline solution (4°C-6°C). In one series we studied myocardial blood flow and arteriovenous differences in oxygen, glucose, lactate, glutamate, and alanine during 60 minutes of postcardioplegic blood reperfusion. In this series captopril-treated hearts were reperfused with captopril-containing blood (1 mg/L). In another series we obtained biopsy specimens from the left ventricle throughout 30 hours of hypothermic cardioplegic storage and monitored tissue content of energy-rich phosphates, glycogen, glutamate, and alanine. Results: Captopril increased glutamate and alanine release 11- to 17-fold at the start of reperfusion ( P < .001). Furthermore, captopril increased myocardial oxygen and glucose uptake during reperfusion ( P < .001 for both), whereas lactate release and myocardial blood flow were unaffected by captopril. At the start of reperfusion, there was a positive correlation between glutamate release and glucose uptake in captopril-treated hearts ( r = 0.66, P = .05). We found no statistically significant differences between captopril and control hearts in tissue content of adenosine triphosphate, glycogen, glutamate, alanine, or lactate during 30 hours of cardioplegic storage. Conclusions: The metabolic effects of captopril are strictly related to reperfusion, during which oxidative metabolism of glucose is improved. The captopril-induced increase in glutamate and alanine release at the start of reperfusion after cardioplegic storage may reflect a switch in metabolism of glucose-related amino acids. (J Thorac Cardiovasc Surg 2000;119:1030-8)