Lactate metabolism in resting and contracting canine skeletal muscle with elevated lactate concentration.

This study was undertaken to quantitatively account for the metabolic disposal of lactate in skeletal muscle exposed to an elevated lactate concentration during rest and mild-intensity contractions. The gastrocnemius plantaris muscle group (GP) was isolated in situ in seven anesthetized dogs. In two experiments, the muscles were perfused with an artificial perfusate with a blood lactate concentration of ~9 mM while normal blood gas/pH status was maintained with [U-(14)C]lactate included to follow lactate metabolism. Lactate uptake and metabolic disposal were measured during two consecutive 40-min periods, during which the muscles rested or contracted at 1.25 Hz. Oxygen consumption averaged 10.1 +/- 2.0 micromol. 100 g(-1). min(-1) (2.26 +/- 0.45 ml. kg(-1). min(-1)) at rest and 143.3 +/- 16.2 micromol. 100 g(-1). min(-1) (32.1 +/- 3.63 ml. kg(-1). min(-1)) during contractions. Lactate uptake was positive during both conditions, increasing from 10.5 micromol. 100 g(-1). min(-1) at rest to 25.0 micromol. 100 g(-1). min(-1) during contractions. Oxidation and glycogen synthesis represented minor pathways for lactate disposal during rest at only 6 and 15%, respectively, of the [(14)C]lactate removed by the muscle. The majority of the [(14)C]lactate removed by the muscle at rest was recovered in the muscle extracts, suggesting that quiescent muscle serves as a site of passive storage for lactate carbon during high-lactate conditions. During contractions, oxidation was the dominant means for lactate disposal at >80% of the [(14)C]lactate removed by the muscle. These results suggest that oxidation is a limited means for lactate disposal in resting canine GP exposed to elevated lactate concentrations due to the muscle's low resting metabolic rate.     

Dynamics of hepatic lactate and glucose balances during prolonged exercise and recovery in the dog

The present experiments were undertaken to assess dynamics of hepatic lactate and glucose balance in the over-night-fasted dog during 150 min of moderate-intensity treadmill exercise and 90 min of exercise recovery. Catheters were implanted chronically in an artery and portal and hepatic veins 16 days before experimentation. 3-3H-glucose was infused to determine hepatic glucose uptake, as well as tracer-determined glucose production by isotope dilution (Ra). At rest, net hepatic lactate output was 0.33 +/- 0.15 mg.kg-1.min-1 and increased to 2.26 +/- 0.82 mg.kg-1.min-1 after 10 min of exercise, after which it fell such that the liver was a net lactate consumer by the end of exercise and through recovery. In contrast to the rapid release of lactate, net hepatic glucose output rose gradually from 2.58 +/- 0.20 mg.kg-1.min-1 at rest to 8.87 +/- 0.85 mg.kg-1.min-1 after 60 min of exercise, beyond which it did not change significantly until the cessation of exercise. Hepatic glucose uptake at rest was 1.38 +/- 0.42 mg.kg-1.min-1 and did not change appreciably during exercise or recovery. Absolute hepatic glucose output (net glucose output plus uptake) rose from 3.96 +/- 0.45 mg.kg-1.min-1 at rest to 10.20 +/- 1.09 mg.kg-1.min-1 after 60 min of exercise and was 9.65 +/- 1.15 mg.kg-1.min-1 at 150 min of exercise. Ra rose from 3.34 +/- 0.21 mg.kg-1.min-1 to 7.58 +/- 0.73 and 8.59 +/- 0.77 mg.kg-1.min-1 at 60 and 150 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of adrenergic agonists and antagonists on muscle O2 uptake and lactate metabolism

To investigate adrenergic receptor-mediated responses in dog gastrocnemius-plantaris muscle, several catecholamine agonists, isoproterenol, epinephrine, norepinephrine, and phenylephrine, and two antagonists, propranolol and phenoxybenzamine, were given during repetitive, isotonic, tetanic contractions. The response variables that were measured were muscle blood flow, shortening during constant load contractions, and arterial and venous O2 and lactate concentrations. The calculated variables were O2 uptake (VO2), net lactic acid output (L), and power output. In the control experiments, the contractions increased VO2 to approximately 50 times rest by 2 min. Thereafter, shortening, work, and VO2 declined together by 17% at 30 min, indicating muscle fatigue. L increased rapidly to nearly 0.8 mumol X g-1 X min-1 by 2 min, declined to 0.3-0.4 mumol X g-1 X min-1 by 7 min, and was like rest at 15, 22.5, and 30 min. The arterial lactate concentration rose steadily from rest to 30 min of contractions. Epinephrine infusion stopped the decline of VO2 during the contractions, but this effect was not observed with the other agonists. Propranolol decreased VO2 compared with controls at 22.5 and 30 min of contractions. Phenoxybenzamine decreased VO2 compared with controls at all times during contraction, and the decline with time was present. Coinfusion of epinephrine with propranolol reduced the decline in VO2 observed with propranolol alone. Both epinephrine and isoproterenol increased L compared with controls. This epinephrine response was antagonized by propranolol but enhanced by phenoxybenzamine. Both isoproterenol and epinephrine infusions increased arterial lactate concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dichloroacetate on hemodynamic responses to dynamic exercise in dogs.

To determine whether lactic acid production contributes significantly to the cardiac responses to muscular dynamic exercise, we administered intravenous sodium dichloroacetate (32 mumol.kg-1.min-1), a pyruvate dehydrogenase activator that facilitates lactate metabolism via the tricarboxylic cycle, in 12 dogs during two graded levels of treadmill exercise. Similar exercise was carried out in nine normal dogs receiving equimolar doses of NaCl. In the latter group, arterial lactate increased progressively from 0.80 +/- 0.11 (SE) mmol/l at rest to 2.13 +/- 0.28 mmol/l by the end of exercise. In contrast, arterial lactate did not change significantly (0.98 +/- 0.12 to 0.95 +/- 0.11 mmol/l) during exercise in dogs receiving dichloroacetate infusion. Dichloroacetate infusion also reduced the increases in plasma norepinephrine, heart rate, and left ventricular contractile indexes that occurred during exercise, suggesting that the sympathetic cardiac stimulation occurring during exercise may be related to the production of lactic acid. However, dichloroacetate affected neither the net increase in cardiac output nor the relationship between total body oxygen consumption and cardiac output that occurred during exercise. Thus we conclude that lactic acid production is not essential to the increase in cardiac output that occurs during mild-to-moderate exercise.     

Non-esterified long-chain fatty acid metabolism in fed sheep at rest and during exercise

The role of circulating, non-esterified, long-chain fatty acids (NEFA) as a source of energy for the whole animal and skeletal muscle was investigated in fed non-pregnant sheep at rest and during exercise. Infusion of tracer quantities of [1-14C]oleic or [1-14C]stearic acid was combined with the use of arteriovenous difference studies on fed sheep at rest or during a 2 h period of exercise on a belt treadmill moving at 4.5 km h-1. At rest all parameters of NEFA metabolism indicated a minimal role for oxidation. Thus the concentration in plasma (0.07 +/- 0.01 mmol l-1), entry rate (0.08 +/- 0.02 mmol h-1 kg-1 body wt), contribution to whole animal oxidation (1.2 +/- 0.3%) and utilization of NEFA by skeletal muscle (0.046 +/- 0.008 mmol h-1 kg-1 muscle) were all low. Exercise prompted a shift to lipolysis and accordingly the above parameters increased markedly some 13-24-fold. The circulating concentration of ketone bodies showed only a small increase during exercise and consequently the role of ketone bodies as an energy source during exercise was minimal. Glucose utilization by skeletal muscle was considerable in animals at rest and it represented the most significant potential fuel of skeletal muscle. Exercise resulted in a sustained increase of 3-4-fold in the utilization of glucose by skeletal muscle. Thus the traditional view that NEFA and not glucose is a predominant fuel of skeletal muscle of fed sheep should be appraised.     

Acute anemia results in an increased glucose dependence during sustained exercise

We evaluated whether acute anemia results in altered blood glucose utilization during sustained exercise at 26.8 m/min on 0% grade, which elicited approximately 60-70% maximal O2 consumption. Acute anemia was induced in female Sprague-Dawley rats by isovolumic plasma exchange transfusion. Hemoglobin and hematocrit were reduced 33% by exchange transfusion to 8.6 +/- 0.4 g/dl and 26.5 +/- 1%, respectively. Glucose kinetics were determined by primed continuous infusion of [6-3H]glucose. Rates of O2 consumption were similar during rest (pooled means 25.1 +/- 1.8 ml.kg-1.min-1) and exercise (pooled means 46.8 +/- 3.0 ml.kg-1.min-1). Resting blood glucose and lactate concentrations were not different in anemic animals (pooled means 5.1 +/- 0.2 and 0.9 +/- 0.02 mM, respectively). Exercise resulted in significantly decreased blood glucose (4.0 +/- 0.2 vs. 4.6 +/- 0.1 mM) and elevated lactate (6.1 +/- 0.4 vs. 2.3 +/- 0.5 mM) concentrations in anemic animals. Glucose turnover rates (Rt) were not different between anemic and control animals at rest and averaged 58.8 +/- 3.6 mumol.kg-1.min-1. Exercise resulted in a 30% greater increase in Rt in anemic (141.7 +/- 3.2 mumol.kg-1.min-1) than in control animals (111.2 +/- 5.2 mumol.kg-1.min-1). Metabolic clearance rates (MCR = Rt/[glucose]) were not different at rest (11.6 +/- 7.4) but were significantly greater in anemic (55.2 +/- 5.7 ml.kg-1.min-1) than in control animals (24.3 +/- 1.4 ml.kg-1.min-1) during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epinephrine infusion enhances muscle glycogenolysis during prolonged electrical stimulation

To determine the effects of epinephrine (EPI) infusion on muscle glycogenolysis and force production, the quadriceps muscles of both legs in six subjects were intermittently stimulated for 30 min. Contractions lasted 1.6 s (20 Hz) and were separated by 1.6 s of rest. EPI was infused (approximately 0.14 micrograms.kg body wt-1.min-1) in one leg during the last 15 min and the vastus lateralis was biopsied at rest (control leg only) and after 15, 18 (EPI leg only), and 30 min of stimulation. EPI infusion doubled the mole fraction of phosphorylase a (22.5 +/- 4.1 to 44.8 +/- 9.0%) and glycogenolysis (2.16 +/- 0.72 to 5.45 +/- 0.81 mmol glucosyl U.kg dry muscle wt-1.min-1) during stimulation. Muscle glucose 6-phosphate increased from 3.04 +/- 0.17 to 6.43 +/- 0.20 mmol/kg dry muscle wt, and lactate increased from 25.8 +/- 4.4 to 34.3 +/- 4.6 mmol/kg after 3 min of EPI infusion. Isometric force production was unaltered by EPI infusion. These results demonstrate a strong glycogenolytic effect of EPI infusion during prolonged electrical stimulation and suggest that the extra pyruvate formed was converted mainly to lactate. Exclusive anaerobic metabolism of the extra substrate would provide only a 10% increase in total ATP production, possibly accounting for the lack of improvement in force production. We suggest that the decrease in force production during prolonged electrical stimulation is related to decreased excitation of the contractile mechanism rather than inhibition of cross-bridge turnover caused by a shortage of energy or accumulation of hyproducts.     

Effects of catecholamines on lactic acid output during progressive working contractions

Epinephrine and norepinephrine together (E + NE) and epinephrine (E) alone were infused intravenously in stepwise increasing doses during progressive isotonic tetanic contractions. The goal was to mimic, for in situ dog skeletal muscle, the concentrations of these catecholamines in the blood and the contractions during progressive exercise. The concentrations of lactate and O2 in arterial and muscle venous blood, the arterial plasma concentration of E and NE, PO2 in arterial and muscle venous blood, and the venous outflow were measured. The infusions caused a rise in plasma E and NE like those seen in progressive exercise. Compared with no-infusion controls, the E + NE infusions and the E alone infusion resulted in significant increases in maximal lactic acid output by the muscles during the contractions from 0.24 mumol X g-1 X min-1 in the controls to 0.44 and 0.54 mumol X g-1 X min-1 during E + NE and E alone infusions, respectively. The venous O2 concentrations and partial pressures were not reduced by the infusions. Both infusions resulted in a rise of arterial lactate concentration that could not be accounted for by the lactic acid output of the contracting muscles. The E alone infusions were associated with a rise in maximal O2 uptake during the contractions. Since the effects of the E + NE and E alone infusions were similar, it was suggested that E is more active than NE. It was suggested that E also increased lactic acid production in tissues other than the working muscles.     

Acute anemia increases lactate production and decreases clearance during exercise

We evaluated whether elevated blood lactate concentration during exercise in anemia is the result of elevated production or reduced clearance. Female Sprague-Dawley rats were made acutely anemic by exchange transfusion of plasma for whole blood. Hemoglobin and hematocrit were reduced 33%, to 8.6 +/- 0.4 mg/dl and 26.5 +/- 1.1%, respectively. Blood lactate kinetics were studied by primed continuous infusion of [U-14C]lactate. Blood flow distribution during rest and exercise was determined from injection of 153Gd- and 113Sn-labeled microspheres. Resting blood glucose (5.1 +/- 0.2 mM) and lactate (1.9 +/- 0.02 mM) concentrations were not different in anemic animals. However, during exercise blood glucose was lower in anemic animals (4.0 +/- 0.2 vs. 4.6 +/- 0.1 mM) and lactate was higher (6.1 +/- 0.4 vs. 2.3 +/- 0.5 mM). Blood lactate disposal rates (turnover measured with recyclable tracer, Ri) were not different at rest and averaged 136 +/- 5.8 mumol.kg-1.min-1. Ri was significantly elevated in both control (260.9 +/- 7.1 mumol.kg-1.min-1) and anemic animals (372.6 +/- 8.6) during exercise. Metabolic clearance rate (MCR = Ri/[lactate]) did not differ during rest (151 +/- 8.2 ml.kg-1.min-1); MCR was reduced more by exercise in anemic animals (64.3 +/- 3.8) than in controls (129.2 +/- 4.1). Plasma catecholamine levels were not different in resting rats, with pooled mean values of 0.45 +/- 0.1 and 0.48 +/- 0.1 ng/ml for epinephrine (E) and norepinephrine (NE), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of contraction frequency on the contractile and noncontractile phases of muscle venous blood flow.

The purpose of this study was to test the hypothesis that increasing muscle contraction frequency, which alters the duty cycle and metabolic rate, would increase the contribution of the contractile phase to mean venous blood flow in isolated skeletal muscle during rhythmic contractions. Canine gastrocnemius muscle (n = 5) was isolated, and 3-min stimulation periods of isometric, tetanic contractions were elicited sequentially at rates of 0.25, 0.33, and 0.5 contractions/s. The O2 uptake, tension-time integral, and mean venous blood flow increased significantly (P < 0.05) with each contraction frequency. Venous blood flow during both the contractile (106 +/- 6, 139 +/- 8, and 145 +/- 8 ml x 100 g-1 x min-1) and noncontractile phases (64 +/- 3, 78 +/- 4, and 91 +/- 5 ml x 100 g-1 x min-1) increased with contraction frequency. Although developed force and duration of the contractile phase were never significantly different for a single contraction during the three contraction frequencies, the amount of blood expelled from the muscle during an individual contraction increased significantly with contraction frequency (0.24 +/- 0.03, 0.32 +/- 0.02, and 0.36 +/- 0.03 ml x N-1 x min-1, respectively). This increased blood expulsion per contraction, coupled with the decreased time in the noncontractile phase as contraction frequency increased, resulted in the contractile phase contribution to mean venous blood flow becoming significantly greater (21 +/- 4, 30 +/- 4, and 38 +/- 6%) as contraction frequency increased. These results demonstrate that the percent contribution of the muscle contractile phase to mean venous blood flow becomes significantly greater as contraction frequency (and thereby duty cycle and metabolic rate) increases and that this is in part due to increased blood expulsion per contraction.     

Short-term training attenuates muscle TCA cycle expansion during exercise in women.

Muscle glycogenolytic flux and lactate accumulation during exercise are lower after 3-7 days of "short-term" aerobic training (STT) in men (e.g., Green HJ, Helyar R, Ball-Burnett M, Kowalchuk N, Symon S, and Farrance B. J Appl Physiol 72: 484-491, 1992). We hypothesized that 5 days of STT would attenuate pyruvate production and the increase in muscle tricarboxylic acid cycle intermediates (TCAI) during exercise, because of reduced flux through the reaction catalyzed by alanine aminotransferase (AAT; pyruvate + glutamate <--> 2-oxoglutarate + alanine). Eight women [22 +/- 1 yr, peak oxygen uptake (Vo2 peak) = 40.3 +/- 4.6 ml. kg-1. min-1] performed seven 45-min bouts of cycle exercise at 70% Vo2 peak over 9 days (1 bout/day; rest only on days 2 and 8). During the first and last bouts, biopsies (vastus lateralis) were obtained at rest and after 5 and 45 min of exercise. Muscle glycogen concentration was approximately 50% higher at rest after STT (493 +/- 38 vs. 330 +/- 20 mmol/kg dry wt; P 相似文献   

Decreased reliance on lactate during exercise after acclimatization to 4,300 m

We hypothesized that the increased exercise arterial lactate concentration on arrival at high altitude and the subsequent decrease with acclimatization were caused by changes in blood lactate flux. Seven healthy men [age 23 +/- 2 (SE) yr, wt 72.2 +/- 1.6 kg] on a controlled diet were studied in the postabsorptive condition at sea level, on acute exposure to 4,300 m, and after 3 wk of acclimatization to 4,300 m. Subjects received a primed-continuous infusion of [6,6-2D]glucose (Brooks et al. J. Appl. Physiol. 70:919-927, 1991) and [3-13C]lactate and rested for a minimum of 90 min followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the sea level peak O2 consumption (VO2peak; 65 +/- 2% of both acute altitude and acclimatization). During rest at sea level, lactate appearance rate (Ra) was 0.52 +/- 0.03 mg.kg-1.min-1; this increased sixfold during exercise to 3.24 +/- 0.19 mg.kg-1.min-1. On acute exposure, resting lactate Ra rose from sea level values to 2.2 +/- 0.2 mg.kg-1.min-1. During exercise on acute exposure, lactate Ra rose to 18.6 +/- 2.9 mg.kg-1.min-1. Resting lactate Ra after acclimatization (1.77 +/- 0.25 mg.kg-1.min-1) was intermediate between sea level and acute exposure values. During exercise after acclimatization, lactate Ra (9.2 +/- 0.7 mg.kg-1.min-1) rose from resting values but was intermediate between sea level and acute exposure values. The increased exercise arterial lactate concentration response on arrival at high altitude and subsequent decrease with acclimatization are due to changes in blood lactate appearance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin does not mediate the attenuation of fatigue associated with glucose infusion in rat plantaris muscle.

Glucose infusion attenuates fatigue in rat plantaris muscle stimulated in situ, and this is associated with a better maintenance of electrical properties of the fiber membrane (Karelis AD, Péronnet F, and Gardiner PF. Exp Physiol 87: 585-592, 2002). The purpose of the present study was to test the hypothesis that elevated plasma insulin concentration due to glucose infusion ( approximately 900 pmol/l), rather than high plasma glucose concentration ( approximately 10-11 mmol/l), could be responsible for this phenomenon, because insulin has been shown to stimulate the Na+-K+ pump. The plantaris muscle was indirectly stimulated (50 Hz, for 200 ms, 5 V, every 2.7 s) via the sciatic nerve to perform concentric contractions for 60 min, while insulin (8 mU x kg-1x min-1: plasma insulin approximately 900 pmol/l) and glucose were infused to maintain plasma glucose concentration between 4 and 6 [6.2 +/- 0.4 mg x kg-1x min-1: hyperinsulinemic-euglycemic (HE)] or 10 and 12 mmol/l [21.7 +/- 1.1 mg. kg-1. min-1: hyperinsulinemic-hyperglycemic clamps (HH)] (6 rats/group). The reduction in submaximal dynamic force was significantly (P < 0.05) less with HH (-53%) than with HE and saline only (-66 and -70%, respectively). M-wave characteristics were also better maintained in the HH than in HE and control groups. These results demonstrate that the increase in insulin concentration is not responsible for the increase in muscle performance observed after the elevation of circulating glucose.     

Effects of training on lactate production and removal during progressive exercise in humans.

To determine whether the reduced blood lactate concentrations [La] during submaximal exercise in humans after endurance training result from a decreased rate of lactate appearance (Ra) or an increased rate of lactate metabolic clearance (MCR), interrelationships among blood [La], lactate Ra, and lactate MCR were investigated in eight untrained men during progressive exercise before and after a 9-wk endurance training program. Radioisotope dilution measurements of L-[U-14C]lactate revealed that the slower rise in blood [La] with increasing O2 uptake (VO2) after training was due to a reduced lactate Ra at the lower work rates [VO2 less than 2.27 l/min, less than 60% maximum VO2 (VO2max); P less than 0.01]. At power outputs closer to maximum, peak lactate Ra values before (215 +/- 28 mumol.min-1.kg-1) and after training (244 +/- 12 mumol.min-1.kg-1) became similar. In contrast, submaximal (less than 75% VO2max) and peak lactate MCR values were higher after than before training (40 +/- 3 vs. 31 +/- 4 ml.min-1.kg-1, P less than 0.05). Thus the lower blood [La] values during exercise after training in this study were caused by a diminished lactate Ra at low absolute and relative work rates and an elevated MCR at higher absolute and all relative work rates during exercise.     

Skeletal muscle glycogenolysis, glycolysis, and pH during electrical stimulation in men

Glycogenolytic and glycolytic rates were estimated and muscle pH (pHm) was measured in electrically stimulated quadriceps femoris muscles of seven men. Leg blood flow was occluded and muscles were stimulated 64 times at 20 Hz, with contractions lasting 1.6 s and separated by pauses of 1.6 s. Muscle biopsies were obtained at rest and following 16, 32, 48, and 64 contractions. Glycolytic intermediates and several modulators of the glycolytic enzyme phosphofructokinase (PFK) were measured. Glycogenolytic and glycolytic rates were 1.68 and 1.26 mmol glucosyl units X kg dry muscle-1 X S-1 contraction time during the initial 16 contractions and pHm decreased from 7.00 +/- 0.01 to 6.70 +/- 0.03. During the subsequent 32 contractions both glycogenolytic and glycolytic rates were maintained at approximately 0.70 mmol X kg-1 X S-1 and pHm decreased to 6.45 +/- 0.04. In the final 16 contractions, both rates were very low and pHm was unchanged. Therefore, PFK remained active despite increasing acidity until pHm decreased to approximately 6.45. We conclude that increases in the concentrations of several positive modulators partially reverses pH-dependent ATP inhibition of PFK in vivo, permitting glycolytic activity to continue in the pHm range of 6.70-6.45.     

Core stabilization exercises enhance lactate clearance following high-intensity exercise

Dynamic activities such as running, cycling, and swimming have been shown to effectively reduce lactate in the postexercise period. It is unknown whether core stabilization exercises performed following an intense bout would exhibit a similar effect. Therefore, this study was designed to assess the extent of the lactate response with core stabilization exercises following high-intensity anaerobic exercise. Subjects (N = 12) reported twice for testing, and on both occasions baseline lactate was obtained after 5 minutes of seated rest. Subjects then performed a 30-second Wingate anaerobic cycle test, immediately followed by a blood lactate sample. In the 5-minute postexercise period, subjects either rested quietly or performed core stabilization exercises. A final blood lactate sample was obtained following the 5-minute intervention period. Analysis revealed a significant interaction (p = 0.05). Lactate values were similar at rest (core = 1.4 +/- 0.1, rest = 1.7 +/- 0.2 mmol x L(-1)) and immediately after exercise (core = 4.9 +/- 0.6, rest = 5.4 +/- 0.4 mmol x L(-1)). However, core stabilization exercises performed during the 5-minute postexercise period reduced lactate values when compared to rest (5.9 +/- 0.6 vs. 7.6 +/- 0.8 mmol x L(-1)). The results of this study show that performing core stabilization exercises during a recovery period significantly reduces lactate values. The reduction in lactate may be due to removal via increased blood flow or enhanced uptake into the core musculature. Incorporation of core stability exercises into a cool-down period following muscular work may result in benefits to both lactate clearance as well as enhanced postural control.     

Respiratory alkalosis: no effect on blood lactate decline or exercise performance

It was the purpose of this study to determine the effects of respiratory alkalosis before and after high intensity exercise on recovery blood lactate concentration. Five subjects were studied under three different acid-base conditions before and after 45 s of maximal effort exercise: 1) hyperventilating room air before exercise (Respiratory Alkalosis Before = RALB, 2) hyperventilating room air during recovery (Respiratory Alkalosis After = RALA), and 3) breathing room air normally throughout rest and recovery (Control = C). RALB increased blood pH during rest to 7.65 +/- 0.03 while RALA increased blood pH to 7.57 +/- 0.03 by 40 min of recovery. Neither alkalosis treatment had a significant effect on blood lactate concentration during recovery. The peak lactate values of 12.3 +/- 1.2 mmol.L-1 for C, 11.8 +/- 1.2 mmol.L-1 for RALB, and 10.2 +/- 0.9 mmol.L-1 for RALA were not significantly different, nor were the half-times (t 1/2) for the decline in blood lactate concentration; C = 18.2 min, RALB = 19.3 min, and RALA = 18.2 min. In C, RALB and RALA, the change in base excess from rest to postexercise was greater than the concomitant increase in blood lactate concentration, suggesting the presence of a significant amount of acid in the blood in addition to lactic acid. There was no significant difference in either the total number of cycle revolutions (C = 77 +/- 2, RALB = 77 +/- 1) or power output at 5 s intervals between RALB and C during the 45 s.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood lactate responses in incremental exercise as predictors of constant load performance

Seven trained male cyclists (VO2max = 4.42 +/- 0.23 l.min-1; weight 71.7 +/- 2.7 kg, mean +/- SE) completed two incremental cycling tests on the cycle ergometer for the estimation of the "individual anaerobic threshold" (IAT). The cyclists completed three more exercises in which the work rate incremented by the same protocol, but upon reaching selected work rates of approximately 40, 60 and 80% VO2max, the subjects cycled for 60 min or until exhaustion. In these constant load studies, blood lactate concentration was determined on arterialized venous ([La-]av) and deep venous blood ([La-]v) of the resting forearm. The av-v lactate gradient across the inactive forearm muscle was -0.08 mmol.l-1 at rest. After 3 min at each of the constant load work rates, the gradients were +0.05, +0.65* and +1.60* mmol.l-1 (*P less than 0.05). The gradients after 10 min at these same work rates were -0.09, +0.24 and +1.03* mmol.l-1. For the two highest work rates taken together, the lactate gradient was less at 10 min than 3 min constant load exercise (P less than 0.05). The [La-]av was consistently higher during prolonged exercise at both 60 and 80% VO2max than that observed at the same work rate during progressive exercise. At the highest work rate (at or above the IAT), time to exhaustion ranged from 3 to 36 min in the different subjects. These data showed that [La-] uptake across resting muscle continued to increase to work rates above the IAT. Further, the greater av-v lactate gradient at 3 min than 10 min constant load exercise supports the concept that inactive muscle might act as a passive sink for lactate in addition to a metabolic site.     

Abnormal oxidative metabolism and O2 transport in muscle phosphofructokinase deficiency

Humans who lack availability of carbohydrate fuels may provide important models for the study of physiological control mechanisms. We compared seven patients who had unavailability of muscle glycogen and blood glucose as oxidative fuels due to muscle phosphofructokinase deficiency (PFKD) with five patients who had a selective defect in long-chain fatty acid oxidation due to carnitine palmitoyltransferase deficiency (CPTD) and with six healthy subjects. Peak cycle exercise work rate, peak O2 uptake (Vo2), and arteriovenous O2 difference were markedly lower (P less than 0.001) for PFKD patients (23 +/- 6 W, 14 +/- 2 ml.min-1.kg-1, and 7.1 +/- 0.5 ml/dl, respectively) than for CPTD patients (142 +/- 33 W, 31 +/- 4 ml.min-1.kg-1, and 15.0 +/- 0.8 ml/dl, respectively) or healthy subjects (171 +/- 17 W, 36 +/- 1 ml.min-1.kg-1, and 16.4 +/- 0.7 ml/dl, respectively). Peak cardiac output (Q) was similar (P less than 0.05) in all three groups, but the slope of increase in Q (l/min) on Vo2 (l/min) from rest to exercise (delta Q/ delta Vo2) was more than twofold greater (P less than 0.001) for PFKD patients (11.2 +/- 1.2) than for CPTD patients (4.6 +/- 0.6) and healthy subjects (4.6 +/- 0.2). Increasing availability of blood-borne oxidative substrates capable of metabolically bypassing the defect at phosphofructokinase (by fasting plus prolonged moderate exercise to increase plasma free fatty acids or by iv lactate infusion) increased peak work rate, Vo2, and arteriovenous O2 difference, lacked consistent effect on peak Q, and normalized delta Q/ delta Vo2 in PFKD patients. The results extend our previous observations in patients with a block in muscle glycogen but not blood glucose oxidation due to phosphorylase deficiency and imply that specific unavailability of muscle glycogen as an oxidizable fuel is primarily responsible for abnormal muscle oxidative metabolism and associated exercise intolerance and exaggerated delta Q/ delta Vo2 in muscle PFKD. The findings also endorse the concept that factors closely linked with muscle oxidative phosphorylation participate in regulating delta Q/ delta Vo2, likely via activation of metabolically sensitive muscle afferents.