1. The importance of the level of tricarboxylic acid cycle intermediates (malate, citrate and fumarate) for energy transduction during exercise has been investigated in six healthy subjects and in two patients with muscle phosphorylase deficiency (McArdle's disease). 2. Healthy subjects cycled for 10 min at low (50 W), moderate [130 ± 6 W (mean ± SEM)] and high (226 ± 12 W) work rates, corresponding to 26, 50 and 80% of their maximal O 2 uptake, respectively. Patients with McArdle's disease cycled for 11–13 min at submaximal (40 W) rates, and to fatigue at maximal work rates of 60–90 W. 3. In healthy subjects, phosphocreatine was unchanged during low work rates, but decreased to 79 and 32% of the initial level during moderate and high work rates. In patients with McArdle's disease, phosphocreatine decreased to 82 and 34% of the initial level during submaximal and peak exercise. Muscle lactate increased in healthy subjects during exercise at moderate and high work rates, but remained low in patients with McArdle's disease. 4. In healthy subjects, tricarboxylic acid cycle intermediates were similar at rest and at low work rates (0.48 ± 0.04 mmol/kg dry weight), but increased to 1.6 ± 0.2 mmol/kg dry weight and 4.0 ± 0.3 mmol/kg dry weight at moderate and high work rates. The tricarboxylic acid cycle intermediate level in patients with McArdle's disease was similar to that in healthy subjects at rest, but was markedly reduced during exercise when compared at the same relative intensity. The peak level of tricarboxylic acid cycle intermediates in patients with McArdle's disease was 22% of that in healthy subjects. However, when compared at the same absolute workload, tricarboxylic acid cycle intermediates were similar in patients with McArdle's disease and in healthy subjects. 5. The decrease in glutamate and increase in alanine suggest that the alanine aminotransaminase reaction was the major anaplerotic process in healthy subjects. However, in patients with McArdle's disease ( n = 1), muscle alanine remained unchanged and the purine nucleotide cycle may instead be the route of a limited anaplerosis during maximal exercise. The muscle content of glutamate and glutamine ( n = 1) was markedly reduced in patients with McArdle's disease. 6. It is concluded that the tricarboxylic acid cycle intermediate level is related to the work rate in healthy subjects, and that the attenuated peak level in patients with McArdle's disease may be a limitation for aerobic energy transduction.

1. Local skeletal muscle blood flow was monitored using the microdialysis ethanol technique and 133 Xe clearance during intermittent isometric contractions (5 s on/10 s off) of the thigh at 0–60% of the maximal voluntary isometric contraction force. 2. A linear increase in blood flow over a 25-fold range was detected using both l33 Xe clearance and the microdialysis ethanol technique. 3. The median correlation coefficient between percentage maximal voluntary isometric contraction force and the ethanol outflow/inflow ratio, a marker of blood flow, was r = −0.98 (−0.94 to −0.99) (median and range, n = 6). The corresponding correlation coefficient for 133 Xe clearance was r = 0.97 (0.92–0.98), the correlation coefficient between the ethanol outflow/inflow ratio and 133 Xe clearance being r = −0.92 (−0.89 to −0.94). 4. Dialysate glucose concentration, although affected by blood flow, was not always significantly correlated with blood flow changes ( r = 0.70; 0.51-0.95). 5. It may be concluded that the ethanol technique provides a valid measure of changes in local skeletal muscle blood flow. The data furthermore show that a linear increase in thigh skeletal muscle blood flow exists during the studied protocol of intermittent isometric contractions.

1. The exchange of plasma amino acids and glucose, lactate, glycerol and 3-hydroxybutyrate in the leg was studied in otherwise healthy patients undergoing elective cholecystectomy. 2. Seven patients were given a constant intravenous infusion of glucose at a rate of 1.1 mmol/min throughout the study. Seven other patients who received normal saline only served as a control group. 3. Measurement of leg blood flow and arterio-femoral venous differences of amino acids and other energy metabolites were made on four occasions: (I) before surgery, (II) 10 min after skin incision, (III) at the end of surgery, and (IV) 30 min after the end of anaesthesia. 4. The release of amino acids from the leg was comparable in the two groups before and during the early part of surgery. At the end of surgery the release of several individual amino acids, as well as the total release of amino acids, from the leg was higher in the patients given glucose infusion compared with the control patients. 5. The infusion of glucose prevented the intraoperative rise in arterial levels and uptake of 3-hydroxybutyrate in the leg. A high release of amino acids at the end of surgery was thus associated with low arterial levels of 3-hydroxybutyrate while the reverse pattern was seen in the control patients. 6. These effects of glucose infusion were qualitatively different from those seen in uninjured post-absorptive man.

1. A thermodilution method was developed for the determination of human leg blood flow. The method is based on bolus injection of an indicator distally into the femoral vein, at room temperature, and recording of the dilution curve in the same vessel at the level of the inguinal ligament. The blood flow was computed automatically with two thermistors and an integrator. 2. The leg blood flow determined by this method at rest and during exercise at work loads of 50, 100 and 150 W in six healthy subjects was found to agree closely with measurements by an intraarterial indicator-dilution technique. A linear relationship was found between leg blood flow and work. The reproducibility of the blood flow determinations, expressed as the coefficient of variation for a single determination, was 12·9 at rest and 5·3 or less during exercise. 3. The method was used in two patients with occlusive arterial disease of the leg. Extremely low leg blood flows were found in these patients when they were forced to interrupt the exercise by severe calf pain.

1. In a group of nine middle-aged patients undergoing varicose vein surgery, cardiac output, right atrial, pulmonary arterial and capillary pressures, and leg blood flow were measured after induction of general anaesthesia but before operation, and also during operation before and after blood substitution. 2. Under anaesthesia, the mean preoperative blood flows in the superficial and common femoral arteries were 160 ml/min and 280 ml/min respectively. These flows are comparable with those obtained in other studies under similar conditions but lower than values obtained in conscious subjects. During the operation the leg blood flow decreased by 24%. As cardiac output remained unchanged, the fractional leg blood flow fell. After transfusion of 900 ml of blood the leg blood flow doubled. 3. It is concluded that anaesthesia, surgical trauma and variations in blood volume greatly influence the leg blood flow and that an adequate substitution of operative blood loss is of utmost importance to achieve an optimum peripheral circulation.

1. The influence of ethanol administration on the metabolism of non-esterified fatty acids (NEFA) and on the utilization of blood-borne substrates and stored glycogen by leg muscles was examined in nine young healthy subjects at rest and during 40 min bicycle ergometer exercise at 50% of maximal capacity. Ethanol was administered by a constant-rate intravenous infusion (6 mmol/min), giving an arterial concentration within the range of 9·3–15·6 mmol/l. Turnover of NEFA and regional exchange were evaluated with [ 14 C]oleic acid, and muscle metabolites were analysed from needle biopsy samples. 2. Leg blood flow was not altered by ethanol. Alanine in arterial blood was reduced by approximately 25% after ethanol administration during exercise. A slight decrease in the concentration of NEFA in arterial plasma was observed after ethanol, associated with an increase in the fractional turnover of oleic acid, indicating an increased removal of NEFA from the plasma. The rate of uptake of NEFA in the leg was only slightly decreased. 3. The total glycogen depletion in leg muscle during exercise was not influenced by ethanol. The pattern of glycogen utilization in different muscle fibres was changed by ethanol and found to be dependent on the fibre composition of the respective subject. In the control experiments, but not after ethanol administration, a negative correlation was observed between glycogen utilization during exercise and the fraction of type I fibres. 4. It is concluded that ethanol administration during exercise (a) decreases leg uptake of NEFA due to a lower concentration of NEFA in plasma, although this lower uptake is compensated by an increased fractional oxidation, (b) does not influence total glycogen depletion in leg muscle, (c) changes the pattern of glycogen utilization in different muscle fibres, (d) influences only to a small extent the energy supply to working muscles, the most predominant isolated effect being on inhibition of the lactate release.

1. Central and regional haemodynamics and leg metabolism at rest, during and after a prolonged exercise were studied in seven untreated hypertensive males before and after a long-term treatment (6 weeks) with an unselective β-receptor-blocking drug (alprenolol). 2. Alprenolol treatment (200–400 mg, twice daily) decreased arterial blood pressure at rest and during exercise; it reduced heart rate in relation to drug plasma concentrations during and after exercise; it left cardiac output unchanged; it reduced leg blood flow at rest, but had no effect on leg blood flow during exercise. 3. Alprenolol treatment also decreased lipolysis and lactate release in relation to drug plasma concentrations during exercise.

1. A dye-dilution method has been developed for the determination of leg blood flow in man. The method is based on the infusion of indicator into the distal part of the femoral vein with blood sampling from the same vein at the level of the inguinal ligament. Catheterization of the femoral artery is not required. Evidence of adequate mixing of dye and blood is presented, based on the finding of the same dye concentration in samples from two different levels in the femoral vein. 2. Leg blood flow measured by this technique at rest and during exercise in six healthy subjects was found to agree closely with simultaneous determinations with an intra-arterial indicator-dilution technique. The reproducibility of the blood-flow measurements, expressed as the coefficient of variation for a single determination, was 9·8%. 3. A routine procedure is suggested for leg blood-flow determination based on femoral venous dye infusion. Using this procedure, leg blood flow was measured in twelve healthy subjects at rest and during exercise at work loads of 100, 200, 400 and 600 kpm/min. A linear relationship was found between leg blood flow and pulmonary oxygen uptake. 4. The applicability of this method to the study of patients with occlusive arterial disease of the leg is illustrated by findings in two patients before and after vascular reconstruction.

1. An indicator-dilution technique was used to determine human leg blood flow at rest and during exercise. The method is based on the infusion of Indocyanine Green into the femoral artery with blood sampling from the femoral vein at the level of the inguinal ligament. Evidence for mixing of dye and blood is presented, based on the finding of equal dye concentrations at two different sampling levels in the femoral vein. The minimum time of infusion required for equilibration at rest is 3 min and during exercise 1 min 20 s. 2. Leg blood flow was measured in eight healthy athletic subjects at rest and during upright exercise on a bicycle ergometer at 400, 800 and 1200 kpm/min. Linear relationships were found between blood flow on the one hand and work intensity and pulmonary oxygen uptake on the other. 3. Leg oxygen uptake was measured as the product of blood flow and femoral arterio-venous oxygen difference. Linear regressions were found for leg oxygen uptake in relation to both work intensity and pulmonary oxygen uptake. Leg mechanical efficiency during exercise averaged 34%. 4. A formula for the approximate calculation of leg blood flow is suggested, based on the pulmonary oxygen uptake and the femoral arterio-venous oxygen difference.