Lactate Exchange Research Articles

Partial purification and reconstitution of the sarcolemmal L-lactate carrier from rat skeletal muscle.

Purified sarcolemmal membranes from mixed rat hindlimb muscle were solubilized with octylglucoside and the extract subjected to hydroxylapatite (HA) chromatography. Following protein elution with a sodium phosphate gradient and detergent removal by dialysis, the HA eluate was reconstituted into asolectin liposomes using a freeze-thaw procedure. Specific L-[14C]lactate transport activity eluting from the 0.2 M sodium phosphate fraction was 30-fold higher compared with native sarcolemmal vesicles (31.64 versus 1.06 nmol/min per mg). The reconstituted carrier exhibited Michaelis-Menten saturation kinetics with Km and Vmax. values of 46.2 +/- 6.6 mM and 498.7 +/- 17.2 nmol/15 s per mg respectively. L-Lactate transport activity was inhibited 57% by preincubation of proteoliposomes with 10 mM alpha-cyano-4-hydroxycinnamate, a known inhibitor of lactate transport. Analysis of the HA eluates by SDS/PAGE showed the presence of a 34 kDa band corresponding to lactate transport activity. Reconstitution of lactate transport activity eluting from the HA column, together with SDS/PAGE analysis suggests the presence of a 34 kDa polypeptide mediating sarcolemmal lactate exchange in rat skeletal muscle.

Lactate and acid-base exchange during brief intense contractions of skeletal muscle in situ.

Our goal was to design a stimulation-contraction paradigm using an isolated in situ dog gastrocnemius muscle preparation that would provide an experimental model for brief intense intermittent (IC) exercise in humans. Second, acid-base and ion exchanges across the muscle were investigated using four 30-s bouts of isotonic tetanic contractions (2 s-1, 100-ms train, 50 impulses/s) with 4 min of rest between bouts. During the bouts, peak power output (W) was 18.2 mW/g in the first bout; it declined by 4.4% by the fourth bout and by 12-16% in each bout. Compared with repetitive continuous contractions (CC) at maximal O2 uptake (VO2), W was greater and VO2 (approximately 3.5 mumol.g-1.min-1) and CO2 production (approximately 4.5 mumol.g-1.min-1) were less with IC. Venous-arterial (v-a) differences and lactate output peaked immediately after each bout and were not different from the values reported for CC at maximal VO2. Thus, with IC, VO2/W was lower and the CO2 production/VO2 and lactate output/VO2 ratios were greater than those seen with CC. These differences suggest that this stimulation-contraction paradigm may be an appropriate model for brief intense exercise. The v-a [H+] difference was a direct result of the v-a PCO2 difference. The venous strong ion difference was always greater than or equal to the arterial strong ion difference because the v-a [Cl-] difference was opposite and greater than the v-a lactate concentration difference, whereas the v-a [Na+] and [K+] differences were small.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic threshold in wheelchair athletes with cerebral palsy: validity and reliability.

This study examined the validity and reliability of the anaerobic threshold (AT) using blood lactate (ATLa) and respiratory gas exchange (ATg) criteria during cycle ergometry (CE) and wheelchair ergometry (WE) in athletes with spastic cerebral palsy (CP). Eleven subjects attempted a discontinuous incremental test protocol, two minutes work interspersed with one minute rest, twice each on the CE and WE. Only five out of the 11 subjects were able to complete the CE tests, whereas all the subjects were able to complete the WE test. Inadequate hip flexion due to muscle spasticity was the primary limiting factor during the CE tests. Although the maximal aerobic power using this protocol was reliable during WE (r = 0.89, p < .05), the validity and reliability of the AT identified by two independent evaluators using these two techniques was questionable. Evaluator 1 was able to identify ATLa and ATg in seven out of the 11 cases, whereas evaluator 2 was successful in five and seven cases, respectively. It is unclear from these results whether the poor validity and reliability of the AT was due to the discontinuous test protocol used, or whether it was due to inconsistencies in the rate of lactate diffusion from the muscle into the blood due to variations in muscle spasticity during the test.

Heat stress does not modify lactate exchange and removal abilities during recovery from short exercise

Arterial and femoral venous lactate concentrations were measured before, during, and after short intermittent exercise (55-118% of maximal O2 consumption) in thermoneutral (N, 25 degrees C, 10.5 Torr) and hot (H, 45 degrees C, 17.5 Torr) conditions. The thermal load induced significantly higher heart rate and rectal temperature in H relative to N. All the arterial lactate (La) recovery curves were fitted to an equation containing two exponential time functions of the form La(t) = La(0) + A1a(1 - e-gamma 1at) + A2a(1 - e-gamma 2at) where the velocity constants gamma 1a and gamma 2a are the body's overall ability to exchange and remove lactate after exercise, respectively, and t is time. There was no significant difference in these constants, regardless of thermal conditions. The arterial lactate concentration at the end of exercise, the peak lactate concentration during recovery, the amplitudes A1a and A2a of the biexponential function, and the arteriofemoral venous lactate concentration difference during recovery were not significantly different in H relative to N. However, measured and computed arterial lactate concentrations during recovery, especially at the end of the tests, were higher in H (P < 0.04). The more elevated lactate concentrations in H at rest at the end of recovery denote a higher basal lactate production, and they were not due to muscle hypoxia.

Ovine fetal placental lactate exchange and decarboxylation at midgestation

In a study of the metabolic implications of the large placental-to-fetal mass ratio that characterizes early fetal development, fetal plasma lactate disposal rate and CO2 production from fetal plasma lactate by fetus and placenta were measured in six midgestation (71-80 days) pregnant sheep. A constant fetal intravenous infusion of L-[U-14C]lactate and 3H2O was given to establish fetal steady-state lactate specific activity and to measure uterine and umbilical blood flows. Fetal and placental weights were 158.6 +/- 19.7 and 441.9 +/- 32.7 g, respectively. There was a significant net lactate flux into the uterine circulation (31 +/- 4.3 mumol/min, P < 0.01) but no measurable umbilical uptake. Fetal plasma lactate disposal rate was 21.2 +/- 2.7 mumol/min, approximately one-half of which represented fetal lactate flux into the placenta (9.9 +/- 1.9 mumol/min). The oxidation rate of tracer lactate carbon to 14CO2 by placenta plus fetus was 72.6 +/- 4.7% of the infused tracer and was fairly evenly distributed between the placenta and the fetus (42.4 +/- 3.9 vs. 30.3 +/- 2.2%). The midgestation placenta metabolizes and produces fetal plasma lactate at rapid and nearly equal rates. This contrasts with the late-gestation placenta, which makes a small contribution to fetal lactate disposal and is a major net source of fetal lactate.

Lactate exchange and removal abilities in sickle cell patients and in untrained and trained healthy humans.

Arterial blood lactate concentrations obtained on seven black males with hemoglobin sickle cell disease (SC) before, during, and after graded bicycle exercise up to exhaustion were compared with those of seven untrained (HU) and seven trained (HT) healthy males of the same ethnic origin. Lactate recovery curves were fitted by a biexponential time function consisting of a rapidly increasing and a slowly decreasing component. Higher work rates were reached by the HU and HT than by the SC group. Blood lactate rose distinctly over the corresponding preexercise resting values after the 25-, 50-, and 100-W exercise steps for the SC, HU, and HT groups, respectively. The arterial oxygen content was significantly lower for the SC than for the HU group at rest and at the end of exercise. The velocity constants of the slowly decreasing component of the lactate recovery curves were similar for the SC, HU, and HT groups despite the fact that they cycled up to different absolute work rates. The velocity constant of the rapidly increasing component was significantly higher for the HT. In terms of the functional meaning given to these constants and in view of their inverse relationship with absolute work rate (Freund et al. J. Appl. Physiol. 61: 932-939, 1986), these results indicate that, relative to the HU, the HT and the SC display improved and impaired abilities, respectively, to exchange and to remove lactate.

Glycerol and lactate uptake in human forearm

Arteriovenous differences for lactate and glycerol reported across the human forearm are inconsistent in direction and magnitude. Such inconsistency could represent the effects of differing forearm compositions. The hypothesis was tested by examination of 37 studies of forearm arteriovenous differences for lactate, glycerol, glucose, and oxygen (only measured in 25 studies) in 23 normal subjects after overnight fast. In 16 studies, glycerol was taken up rather than released by the forearm, and in 12 of these the arteriovenous difference was greater than could be accounted for by analytical variation. The arteriovenous differences for glycerol and lactate were positively correlated ( r = .44, P < .01). The hypothesis that glycerol and lactate uptake might reflect a more “oxidative” forearm was not borne out, since neither glycerol nor lactate arteriovenous differences correlated with that for oxygen, although oxygen and glucose arteriovenous differences and fluxes were correlated (fluxes: r = .60, P < .01). The arteriovenous difference for glycerol was positively related to body mass index, arguing against a variable contribution from fat. The hypothesis that the direction of glycerol and lactate exchange would reflect the forearm composition was not borne out by the analysis of repeated studies on the same individual, which showed that the variation within subjects was not significantly less than that between subjects. Therefore, we conclude that in approximately 40% of studies in normal subjects after an overnight fast, the forearm will show glycerol uptake, although we have been unable to identify any physiological reason for this phenomenon. Peripheral glycerol uptake has implications for studies in which glycerol release is taken as a measure of lipolysis.

Current Concepts in Lactate Exchange

There are several goals to this introductory paper in the symposium proceedings, “Current Concepts in Lactate Exchange.” First, an attempt is made to set the historical context for the symposium and foreshadow how the paper of each participant contributes to our contemporary understanding of the field. As implied in the symposium title, an emphasis will be placed on the exchange of lactate for other metabolites and ions so that utilization can be temporally and spatially disassociated from formation. Thus, rather than a dead-end metabolite, which only accumulates during exercise, there appears to be great usefulness in the formation, exchange between cells, blood and organs, and utilization of lactic acid (lactate). Specific papers will deal with aspects of lactate release and uptake by skeletal muscle, hepatic lactate balance, the flux of dietary carbohydrate through various lactate pools in the synthesis of liver glycogen, lactate metabolism in the heart, properties of the sarcolemmal lactate transporter, and evolution of a model to predict lactate production from blood measurements. Second, in this review an attempt will be made to present and support a unifying hypothesis (the “lactate shuttle”) in which the various aspects of lactate exchange may be integrated and understood. Emphasis will be placed on showing several corollaries between muscle and whole-body lactate metabolism. These are: temporal dependence on lactate uptake and release, the effects of beta-adrenergic stimulation on lactate formation and release, the effect of prior endurance training on lactate metabolism, the effect of lactate on glucose uptake and utilization, and the role of low oxygen tension (hypoxia) in loosening the control of glycolysis. The formation, exchange, and utilization of lactate represents a central means by which the coordination of intermediary metabolism in diverse tissues and different cells within tissues can be accomplished.

Myocardial blood flow and lactate metabolism at rest and during exercise with reduced arterial oxygen content

The effect of a reduction in arterial oxygen content, equivalent to acute exposure to an altitude of 2300 metres above sea level, on myocardial blood flow and oxygen and lactate exchange was studied by coronary sinus catheterization in 12 healthy men. Measurements were made at rest, during atrial pacing and during submaximal and maximal exercise both breathing air and breathing 15% oxygen (hypoxia). Coronary sinus blood flow was measured by thermodilution and the possibility of a simultaneous uptake and release of lactate by the heart was calculated using intravenous infusion of 14C lactate. At all levels of cardiac power output myocardial oxygen consumption was the same during hypoxia as during air breathing. At rest this was achieved entirely by a more complete extraction of oxygen from the coronary blood, during maximal exercise entirely by a greater coronary sinus blood flow, while at intermediate levels of cardiac power output a combination of these mechanisms prevailed. At rest and during submaximal work myocardial lactate extraction was lower with hypoxia than air breathing suggesting a change in myocardial redox state, while the 14C lactate data suggested no significant lactate release or possibly limited areas with some lactate production. During maximal exercise, however, there was no difference in myocardial lactate net extraction between hypoxia and air breathing, which together with the greater blood flow suggests that the heart has a 'coronary flow reserve' permitting maximal exercise at moderate altitude without anaerobic myocardial metabolism.

Regulation of hepatic lactate balance during exercise

The rate of exchange of lactate across the liver gives important insights into intracellular processes during muscular work. At the onset of exercise hepatic glycogenolysis increases rapidly, resulting in high rates of glycolytic flux and a transient rise in lactate output. With increasing exercise duration, gluconeogenesis is accelerated and the liver gradually shifts from a lactate-producing to a lactate-consuming state. Exercise-induced changes in hormone levels are critical in the regulation of hepatic glycogenolysis and gluconeogenesis and, therefore, net hepatic lactate balance. The fall in insulin stimulates hepatic glycogenolysis, glycolytic flux, and, as a result, hepatic lactate output. On the other hand, the stimulatory effects of glucagon on gluconeogenesis elicit an increase in hepatic lactate uptake. The rise in epinephrine may regulate gluconeogenesis during prolonged exercise by stimulating peripheral lactate mobilization, thereby providing gluconeogenic substrate to the liver. Chronic hepatic-denervation leads to an increase in gluconeogenesis and net hepatic lactate uptake at rest without altering total glucose production. However, the response to exercise is unaffected by the absence of hepatic nerves. Hence, the direction and magnitude of the hepatic lactate balance during exercise yields important information regarding flux through the gluconeogenic and glycolytic pathways, such that high rates of gluconeogenesis correspond to accelerated rates of hepatic lactate uptake and high rates of hepatic glycolytic flux lead to increased rates of hepatic lactate output.

Regulation of muscle lactate production

It is not possible to make accurate measurements of muscle lactic acid net exchange during exercise by application of the Fick relationship. To make accurate measurements of lactic acid net exchange, preparations with isolated circulations have been used. Since such preparations utilize relatively small muscles or groups of muscles, the data apply to muscle contractions, not exercise. In exercise, external influences may affect lactate exchange. The net lactic acid exchange (L) of the isolated dog gastrocnemius-plantaris muscle group has been quantified for repetitive twitch and tetanic contractions, progressive contractions, and four repetitions of 30-s intense contractions with 3.5 min of recovery between each. Epinephrine has been infused during repetitive and progressive contractions; modest ischemia and hypoxic hypoxia, and the oxidation-reduction state of mitochondrial cytochrome a-a3 have been investigated. After the initiation of repetitive contractions, L rises transiently to a peak at 3-5 min and then declines to net uptake after 30 min of contractions. The peak L is roughly proportional to VO2. L rises progressively during progressive contractions to levels lower than the peak in repetitive contractions. Epinephrine increases L transiently during repetitive contractions and increases L during progressive contractions. L rises to levels similar to the repetitive peak during the four repeated 30-s bouts. Cytochrome a-a3 was more oxidized during contractions than when at rest. Ischemia has little or no effect on L. Hypoxic hypoxia sufficient to produce hypoxidosis increased L sharply, but transiently. Muscle L reflects the balance between the production of the products of glycolysis and their removal into the mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial lactate metabolism during exercise

The heart consumes lactate under resting conditions in normal healthy people. A limited number of studies have measured lactate exchange across the heart during exercise by using simultaneous arterial and coronary sinus catheterization. In general, exercise results in an increase in the rate of lactate uptake, which is due both to the increases in myocardial blood flow and lactate extraction from rest to exercise. Lactate extraction by the myocardium during submaximal exercise (40-60% VO2max) is largely dependent upon the concentration of lactate in arterial blood. Studies using a continuous infusion of 14C-lactate tracer have demonstrated that essentially all of the lactate taken up during exercise is immediately oxidized to CO2 in the myocardium. In addition, lactate tracer studies indicate that healthy myocardium simultaneously consumes and produces lactate under conditions of net lactate consumption. Moderate intensity exercise (40% VO2max) does not result in an increase in the rate of myocardial lactate production above resting values. Thus, the heart takes up lactate in proportion to the rate of lactate delivery to the myocardium both at rest and during exercise. Exercise that elicits an increase in the arterial lactate concentration above resting values results in an increase in the relative contribution of lactate oxidation to myocardial oxidative metabolism.

Effect of Endurance Swimming on the Lactate Kinetics of Rainbow Trout

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

Effect on whole-body protein synthesis after institution of intravenous nutrition in cancer and non-cancer patients who lose weight

Cancer and non-cancer patients received total parenteral nutrition (TPN) corresponding to either 120% or 200% non-protein energy resting energy expenditure. Whole-body tyrosine flux and leg exchange of various metabolites were measured in the fasted and fed state. Feeding with the moderate TPN rate did not stimulate whole-body protein synthesis in either group, but the high rate did. Both TPN rates switched an efflux of branched-chain aminoacids from the leg to an uptake in both groups, but this did not apply to tyrosine or phenylalanine. Only the high TPN rate stimulated glucose uptake across the leg in both groups. The leg exchanges of lactate, glycerol and free fatty acids were not significantly influenced by moderate or high TPN rates in either group, although changes in arterial concentrations indicated significant exchanges in compartments other than leg tissues. Thus standard TPN is insufficient to stimulate overall protein synthesis in both malnourished cancer and non-cancer patients, which may explain why previous studies have demonstrated insignificant functional effects with nutritional support to cancer patients.

Splanchnic and muscle fructose metabolism during and after exercise

Regional substrate exchange was studied in 12 healthy males during 90 min of bicycle exercise at 30% of maximal O2 consumption with a 20-min recovery. Six subjects received an intravenous fructose infusion (8.5 mmol/min) from 40 min of exercise to the end of recovery. Splanchnic glucose output, muscle glucose uptake, arterial glucose, and insulin were uninfluenced by the infusion. The respiratory exchange ratio rose to 0.93 +/- 0.04, and arterial free fatty acids fell by 50% (P less than 0.05). Fructose was taken up by splanchnic tissues (45% of administered load), leg muscle (28%), and resting muscle (28%). During infusion, arterial lactate and pyruvate rose two- to threefold, and these substrates were released from splanchnic tissues and taken up by exercising and resting muscle. Splanchnic release of lactate, pyruvate, and glucose accounted for 78% of fructose uptake at 90 min of exercise. Uptake of fructose, lactate, and pyruvate accounted for 55% and together with glucose for 103% of the total oxidative metabolism by exercising muscle. The regional fructose uptakes and lactate exchanges persisted throughout recovery. The present results indicate that fructose infusion during leg exercise 1) results in increased carbohydrate oxidation from fructose, lactate, and pyruvate in exercising muscle, 2) exerts a glycogenic effect in resting muscle and liver during exercise and in liver and muscle recovering from exercise, and 3) does not interfere with glucose metabolism, and that fructose transport into muscle differs from that of glucose.

The role of transmembrane pH gradients in the lactic acid induced swelling of astrocytes

The swelling of astrocytes is an important component of the morbidity and mortality associated with ischemic brain trauma. In the ischemic brain, lactic acid levels rise dramatically with a concomitant acidification of the extracellular fluid. In this study we have measured the effects of elevated extracellular lactate and reduced extracellular pH (pH 0) on astrocyte volume using the human astrocyte-derived cell line UC-11MG. Neither elevated lactate nor reduced pH 0 alone increased cell volume, but swelling of about 25% was measured when the cells were exposed simultaneously to 20 mM lactic acid and a reduced pH 0 of 6. The swelling was correlated with an approximately 4-fold increase in intracellular lactate as pH 0 was decreased from 8.0 to 6.0. As pH 0 was decreased intracellular pH also decreased, but much more slowly so that at acidic extracellular pH there was an inwardly directed proton gradient. The measured intracellular lactate concentrations closely followed the theoretical levels predicted by a model in which lactate transport is coupled to the inwardly directed proton gradient. Kinetic studies indicated that lactate transport is saturable with a K m of 3.8 mM, consistent with the model for facilitated cotransport of lactate with a proton or exchange of lactate for a hydroxyl ion. These data suggest that an important mechanism of postischemic astrocytic swelling is a proton driven, active accumulation of lactate to levels that result in a significant osmotic gradient of lactate at acidic pH.

Gut Exchange of Glucose and Lactate in Basal State and After Oral Glucose Ingestion in Postoperative Patients

Glucose uptake by the intestine and its conversion into 3-carbon compounds in the human intestine in the basal state and after an oral glucose load are not understood. Consequently, we studied the arterial and portal venous concentration differences (A-PV) for glucose and glucogenic substrates in the basal state and 3 h after the ingestion of a 100-g glucose load with the catheter technique. Five patients were studied 3-11 days after surgery for gallbladder disease or cancer of the colon or liver. A-PV for glucose in the basal state was 0.12 +/- 0.02 mM (P less than 0.01), indicating net glucose uptake by extrahepatic splanchnic tissues. No net exchange of lactate or pyruvate was detected, but there was release of alanine and uptake of glutamine. After glucose ingestion, glucose was released by the gut, reflecting absorption of the load (mean A-PV for glucose -2.10 +/- 0.04 mM, P less than 0.01). The arterial glucose concentration rose gradually from 4.6 +/- 0.1 mM before glucose ingestion to a plateau at 9.5 +/- 0.7 mM from 90 to 180 min. Glucose ingestion was accompanied by net lactate and alanine release (A-PV -0.16 +/- 0.06 mM and -48 +/- 7 microM, respectively), whereas A-PV for pyruvate did not change. We conclude that, in postoperative patients, there is a significant net glucose uptake by the gastrointestinal tract in the basal state. Glucose ingestion is accompanied by a small release of lactate and alanine from the intestine. However, the estimated net gut formation of lactate and alanine can play only a minor role in the disposal of an oral glucose load.

Gut exchange of glucose and lactate in basal state and after oral glucose ingestion in postoperative patients

Gut exchange of glucose and lactate in basal state and after oral glucose ingestion in postoperative patients

2 CURRENT CONCEPTS IN LACTATE EXCHANGE

There are several goals to this introductory paper in the symposium proceedings, "Current Concepts in Lactate Exchange." First, an attempt is made to set the historical context for the symposium and foreshadow how the paper of each participant contributes to our contemporary understanding of the field. As implied in the symposium title, an emphasis will be placed on the exchange of lactate for other metabolites and ions so that utilization can be temporally and spatially disassociated from formation. Thus, rather than a dead-end metabolite, which only accumulates during exercise, there appears to be great usefulness in the formation, exchange between cells, blood and organs, and utilization of lactic acid (lactate). Specific papers will deal with aspects of lactate release and uptake by skeletal muscle, hepatic lactate balance, the flux of dietary carbohydrate through various lactate pools in the synthesis of liver glycogen, lactate metabolism in the heart, properties of the sarcolemmal lactate transporter, and evolution of a model to predict lactate production from blood measurements. Second, in this review an attempt will be made to present and support a unifying hypothesis (the "lactate shuttle") in which the various aspects of lactate exchange may be integrated and understood. Emphasis will be placed on showing several corollaries between muscle and whole-body lactate metabolism. These are: temporal dependence on lactate uptake and release, the effects of beta-adrenergic stimulation on lactate formation and release, the effect of prior endurance training on lactate metabolism, the effect of lactate on glucose uptake and utilization, and the role of low oxygen tension (hypoxia) in loosening the control of glycolysis. The formation, exchange, and utilization of lactate represents a central means by which the coordination of intermediary metabolism in diverse tissues and different cells within tissues can be accomplished.

Influence of local β‐adrenoceptor blockade on exchange of fat and glucose in the human leg after surgery

The metabolic effects of the local administration of propranolol were determined in seven patients undergoing cholecystectomy. Measurements were carried out in the early postoperative period before and after infusion of 2 mg of intraarterial propranolol into the femoral artery of one leg using the other leg as control. Blood flow and arterio-venous concentration differences for oxygen, glucose, lactate, alanine, glycerol and total FFAs were determined. Uptake and release of FFAs were determined by using a tracer technique. The statistical analyses were based on differences between the test and the control leg in changes following the blockade. Glycerol release was significantly more suppressed in the test leg than in the control leg. No difference between the legs was seen in the uptake of oxygen, FFA and glucose or the release of lactate and alanine. The arterial concentration of propranolol was 6.07 +/- 0.72 ng ml-1 (mean +/- SEM). This study indicates that a local beta-blockade by intra-arterial propranolol infusion after surgery slightly reduces the postoperative lipolysis in leg tissues but does not influence or only marginally influences leg blood flow and oxygen uptake or the exchange of glucose, lactate and alanine after moderate surgical trauma.