Arterio-venous differences of blood acid-base status and plasma sodium caused by intense bicycling

After intense exercise muscle may give off hydrogen ions independently of lactate, perhaps by a mechanism involving sodium ions. To examine this possibility further five healthy young men cycled for 2 min to exhaustion. Blood was drawn from catheters in the femoral artery and vein during exercise and at 1-h intervals after exercise. The blood samples were analysed for pH, blood gases, lactate, haemoglobin, and plasma proteins and electrolytes. Base deficit was calculated directly without using common approximations. The leg blood flow was also measured, thus allowing calculations of the leg's exchange of metabolites. The arterial blood lactate concentration rose to 14.2 +/- 1.0 mmol L-1, the plasma pH fell to 7. 18 +/- 0.02, and the base deficit rose 22% more than the blood lactate concentration did. The femoral-venous minus arterial differences peaked at 1.8 +/- 0.2 mmol L-1 (lactate), -0.24 +/- 0.01 (pH), and 4.5 +/- 0.4 mmol L-1 (base deficit), and -2.5 +/- 0.7 mmol L-1 (plasma sodium concentration corrected for volume changes). Thus, near the end of the exercise and for the first 10 min of the recovery period the leg gave off more hydrogen ions than lactate ions to the blood, and sodium left plasma in proportion to the extra hydrogen ions appearing. The leg's integrated excess release of hydrogen ions of 0.88 +/- 0.45 mmol kg-1 body mass was 67% of the integrated lactate release. Base deficit calculated by the traditional approximate equations underestimated the true value, but the error was less than 10%. We conclude that intense exercise and lactic acidosis may lead to a muscle release of hydrogen ions independent of lactate release, possibly by a Na+,H+ exchange. Hydrogen ions were largely buffered in the red blood cells.     

Power and peak blood lactate at 5050 m with 10 and 30 s ‘all out’ cycling

Anecdotal observations suggest that the reduction in peak lactate accumulation in blood ([La]_{b peak}) after exhausting exercise, in chronic hypoxia vs. normoxia, may be related to the duration of the exercise protocol, being less pronounced after short supramaximal exercise than after incremental exercise (IE) lasting several minutes. To test this hypothesis, six healthy male Caucasians (age 36.8 ± 7.3, x¯ ± SD) underwent three exercise protocols on a cycle ergometer, at sea level (SL) and after 21 ± 10 days at 5050 m altitude (ALT): (1) 10 s, (2) 30 s ‘all out’ exercise and (3) IE leading to exhaustion in ～20–25 min. ‘Average’ power output (p¯) was calculated for 10 or 30 s ‘all out’; maximal power output (P_max) was determined for IE. Lactate concentration in arterialized capillary blood ([La]_b) was measured at rest and at different times during recovery; the highest [La]_b during recovery was taken as [La]_{b peak}. No significant differences in p¯ were observed between SL and ALT, for either 10 or 30 s ‘all out’ exercise; P_max during IE was significantly lower at ALT than at SL. [La]_{b peak} after 10 s ‘all out’ was unaffected by chronic hypoxia (7.0 ± 0.9 at ALT vs. 6.3 ± 1.8 mmol L^–1 at SL). After 30 s ‘all out’ the [La]_{b peak} decrease, at ALT (10.6 ± 0.6 mmol L^–1) vs. SL (12.9 ± 1.4 mmol L^–1), was only ～50% of that observed for IE (6.7 ± 1.6 mmol L^–1 vs. 11.3 ± 2.8 mmol L^–1). Muscle power output and blood lactate accumulation during short supramaximal exercise are substantially unaffected by chronic hypoxia.     

Serial effects of high-resistance and prolonged endurance training on Na+–K+ pump concentration and enzymatic activities in human vastus lateralis

The purpose of this study was to compare two contrasting training models, namely high-resistance training and prolonged submaximal training on the expression of Na⁺–K+ ATPase and changes in the potential of pathways involved in energy production in human vastus lateralis. The high-resistance training group (VO _2peak = 45.3 ± 1.9 mL kg^?1 min^?1, mean ± SE, n = 9) performed three sets of six to eight repetitions maximal, each of squats, leg presses and leg extensions, three times per week for 12 weeks, while the prolonged submaximal training group (VO _2peak = 44.4 ± 6.6 mL kg^?1 min^?1, n = 7) cycled 5–6 times per week for 2 h day^?1 at 68% VO _2peak for 11 weeks. In the HRT group, Na⁺–K⁺ ATPase (pmol g^?1 wet wt), measured with the ³H-ouabain binding technique, showed no change from 0 (289 ± 22) to 4 weeks (283 ± 15), increased (P < 0.05) by 16% at 7 weeks and remained stable until 12 weeks (319 ± 19). For prolonged submaximal training, a 22% increase (P < 0.05) was observed from 0 (278 ± 31) until 3 weeks (339 ± 29) with no further changes observed at either 9 weeks (345 ± 25) or 11 weeks (359 ± 34). In contrast to high-resistance training, where a 15% increase (P < 0.05) was observed, only in the maximal activity of phosphorylase, prolonged submaximal training resulted in increases in malate dehydrogenase, β-hydroxyl-CoA dehydrogenase, hexokinase and phosphofructokinase. In contrast to high-resistance training which failed to result in an increase in VO _2peak, prolonged submaximal training increased VO _2peak by ≈15%. Only for prolonged exercise training was a relationship observed for VO _2peak and Na⁺–K⁺-ATPase (r = 0.59; P < 0.05). Correlations between VO _2peak and mitochondrial enzyme activities were not significant (P > 0.05) for either training programme. It is concluded that although both training programmes stimulate an up-regulation in Na⁺–K⁺ ATPase concentration, only the prolonged submaximal training programme enhances the potential for β-oxidation, oxidative phosphorylation and glucose phosphorylation.     

The ‘lactate paradox’, evidence for a transient change in the course of acclimatization to severe hypoxia in lowlanders

The metabolic response to exercise at high altitude is different from that at sea level, depending on the altitude, the rate of ascent and duration of acclimatization. One apparent metabolic difference that was described in the 1930s is the phenomenon referred to as the ‘lactate paradox’. Acute exposure to hypoxia results in higher blood lactate accumulation at submaximal workloads compared with sea level, but peak blood lactate remain the same. Following continued exposure to hypoxia or altitude, blood lactate accumulation at submaximal work and peak blood lactate levels are paradoxically reduced compared with those at sea level. It has recently been shown, however, that, if the exposure to altitude is sufficiently long, blood lactate responses return to those seen at sea level or during acute hypoxia. Thus, to evaluate the ‘lactate paradox’ phenomenon in relation to time spent at altitude, five Danish lowland climbers were studied at sea level, during acute exposure to hypoxia (10% O₂ in N₂) and 1, 4 and 6 weeks after arrival in the basecamp of Mt Everest (～5400 m, Nepal). Basecamp was reached after 10 days of gradual ascent from 2800 m. Peak blood lactate levels were similar at sea level (11.0 ± 0.7 mmol L^?1) and during acute hypoxia (9.9 ± 0.3 mmol L^?1), but fell significantly after 1 week of acclimatization to 5400 m (5.6 ± 0.5 mmol L^?1) as predicted by the ‘lactate paradox’. After 4 weeks of acclimatization, peak lactate accumulation (7.8 ± 1.0 mmol L^?1) was still lower compared with acute hypoxia but higher than that seen after 1 week of acclimatization. After 6 weeks of acclimatization, 2 days after return to basecamp after reaching the summit or south summit of Mt Everest, peak lactate levels (10.4 ± 1.1 mmol L^?1) were similar to those seen during acute hypoxia. Therefore, these results suggest that the ‘lactate paradox’ is a transient metabolic phenomenon that is reversed during a prolonged period of exposure to severe hypoxia of more than 6 weeks.     

Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V_mean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA V_mean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V_mean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V_mean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s^?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min^?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min^?1) and ΔMCA V_mean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s^?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA V_mean (10.2 ± 2.5 cm s^?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.     

Cardiovascular responses during one- and two-legged exercise in middle-aged men

Eight healthy and regularly physically active men, 44–69 years old, performed one- and two-legged dynamic knee extension exercise at increasing work intensities, including one leading to exhaustion. Leg blood flow increased linearly in relation to work rate, reaching a peak value of 5.1 ±0.4 1 min^-1. With a mean weight of quadriceps femoris of 2.2 ±0.1 kg, a peak perfusion of 2.3 ±0.11 kg^-1 min^-1 was attained. The maximal leg oxygen uptake was 0.72 ±0.071 min^-1 (0.33 ±0.03 1 kg^-1 min^-1). At submaximal work the elevation in limb oxygen uptake accounted for between 70 and 100% of the rise in pulmonary oxygen uptake. Comparing two- with one-legged knee extension the cardiac output was 1.5 1 min^-1 higher at each work level, reaching 13.7±0.7 and 12.3 ± 1.0, respectively at exhaustion, leaving 3.5 and 7.2 1 min^-1 of blood flow to the remaining body (cardiac output –leg blood flow). The mean arterial pressure was 119 ±5 mmHg at rest and increased to 155 mmHg for both test modes at the maximal work rate. The femoral arterial and venous plasma concentrations of lactate, ammonia and noradrenaline were significantly higher for two-legged as compared with one-legged exercise at the maximal load performed. However, the rate of release per leg, for both lactate and ammonia, did not differ between the two test conditions. It is concluded that physically active middle-aged men, with a well-retained muscle mass, can maintain a high skeletal muscle perfusion, similar to that of young males. However, the blood flow is achieved with a higher mean arterial pressure and an elevated sympathetic activity, as reflected by noradrenaline in plasma and spillover from the exercising limb.     

Effect of β-adrenoceptor stimulation on oxygen consumption and triglyceride/fatty acid cycling after exercise

The purpose of this study was to characterize the effects of prolonged β-adrenoceptor stimulation on O₂ uptake and triglyceride/fatty acid (TG/FA) cycling during rest with and without previous exercise. Eight men performed two exercise (90 min cycling at 56 ± 3 (SD)% of maximal O₂ uptake, followed by 4.5 h bed rest) and two rest-control experiments. In one rest and one exercise experiment a bolus dose (5 μg) of the β-adrenoceptor agonist isoprenaline was given immediately after exercise, followed by a continuous infusion (20 ng kg^–1 min^–1), and at the corresponding time in the rest experiment. In the other experiments saline was given instead. The O₂ uptake increased in the post-exercise period both with and without β-stimulation. The total excess post-exercise oxygen consumption (EPOC) was not different between saline (8.1 ± 1.8 (SE) L) and isoprenaline administration (10.8 ± 1.8 L, P = 0.40). Also, the total accumulated increase in O₂ uptake for the 4.5 h period after isoprenaline infusion was not different between the rest (12.5 ± 2.0 L) and the exercise experiments (15.2 ± 1.7 L, P = 0.40). The rate of TG/FA cycling increased after both exercise and isoprenaline treatment, but no interaction effect was found. In conclusion, the increases observed in O₂ uptake and the rate of TG/FA cycling during β-adrenoceptor stimulation were not increased by a previous exercise bout.     

Influence of lactate accumulation of EMG frequency spectrum during repeated concentric contractions

One hundred and twenty consecutive maximal leg extensions at a constant angular velocity of 1.5 radians. s^-1 were performed by nine physical education students. Integrated electromyographic (IEMG) activity and power spectrum density function (PSDF) of the EMG were recorded from m. vastus lateralis, m. vastus medialis and m. rectus femoris using bipolar surface electrodes. Muscle biopsies were obtained from m. vastus lateralis before and after exercise. Tissue samples were analyzed for muscle fiber type distribution and lactate and glycogen concentration. Muscle force and IEMG decreased in parallel over the exercise period. Thus, the IEMG/force ratio was unchanged. Mean power frequency (MPF) of PSDF of the three muscles decreased by 10% (p<0.001) during the initial 25 contractions with no further decline during the latter part of exercise. The relative contribution of the highest bandwidth (130–500 Hz) of the PSDF decreased (p<0.001) between the first and final contractions. Muscle glycogen concentration decreased from 85 ± 23 to 68 ± 22 mmol ± kg^-1 w. w.during the exercise. Muscle and blood lactate concentration averaged 12.1 ± 8.8 mmol ± kg^-1 w. w.and 3.8 ± 0.8 mmol ± l^-1, respectively. The relative changes in MPF and in the highest bandwidth were correlated with muscle lactate concentration and fiber type distribution: in individuals with a high proportion of fast twitch muscle fibers and/or the greatest lactate accumulation, MPF and high frequency components of EMG PSDF decreased most markedly. Reductions in muscle force and IEMG are suggested to be partly due to a decreased motor neuron firing rate. It is discussed whether lactate or associated metabolic changes are influencing the motor unit action potential through feedback processes     

Intraerythrocyte and plasma lactate concentrations during exercise in humans

Summary The purpose of this study was to examine plasma and intraerythrocyte lactate concentrations during graded exercise in humans. Seven adult volunteers performed a maximum O₂ uptake ( ) test on a cycle ergometer. Plasma and intraerythrocyte lactate concentrations (mmol · L⁻¹ of plasma or cell water) were determined at rest, during exercise, and at 15-min post-exercise. The results show that plasma and intraerythrocyte lactate concentrations were not significantly different from each other at rest or moderate (⩽50% ) exercise. However, the plasma concentrations were significantly increased over the intraerythrocyte levels at 75% and 100% . The plasma to red cell lactate gradient reached a mean (±SE) 1.7±0.4 mmol · L⁻¹ of H₂O at exhaustion, and was linearly (r=0.84) related to the plasma lactate concentration during exercise. Interestingly, at 15-min post-exercise the direction of the lactate gradient was reversed, with the mean intraerythrocyte concentration now being significantly increased over that found in the plasma. These results suggest that the erythrocyte membrane provides a barrier to the flux of lactate between plasma and red cells during rapidly changing blood lactate levels. Furthermore, these data add to the growing body of research that indicates that lactate is not evenly distributed in the various water compartments of the body during non-steady state exercise.     

Influence of ruminal water‐loading on renal sodium excretion and water intake following feeding in sheep

We investigated the effect of ruminal water loading before feeding on the natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of chaff drank 1360 ± 150 mL during the 5 h immediately following feeding and increased renal Na excretion. Plasma Na concentration increased by 4 mmol L^–1 and plasma osmolality by 9 mosmol kg^–1 within 1.5 h and remained elevated. A rumen load of water administered before feeding prevented the increases in plasma Na and osmolality without affecting feeding. The natriuresis, water drinking and vasopressin secretion in response to feeding were abolished. Total sodium excreted during the experiment was halved in water‐loaded animals compared with untreated animals (30.4 ± 2.1 mmol^–1 cf. 63.8 ± 2.9 mmol^–1; P < 0.01). Ruminal loading with isotonic saline caused a 33% reduction in postprandial drinking, however, reducing cerebrospinal fluid NaCl concentration abolished postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran appeared to delay the onset of water intake without changing the total volume of water drunk, suggesting a role of plasma volume in initiating drinking. We conclude from the data that central osmoregulatory mechanisms that include increased sodium excretion as well as thirst and vasopressin release are activated following food intake by sheep.     

The role of antidiuretic hormone in cold-induced diuresis in the anaesthetized rat

The aim of this study was to investigate whether the increased diuresis in consequence of hypothermia is due to a depression of the hypothalamic release of antidiuretic hormone (ADH). The plasma concentration of antidiuretic hormone and the effect of intravenous (i.v.) administration of 65 ng kg^?1 desmopressin (selective V₂-receptor agonist) were determined in the anaesthetized rat. In spite of a 50% (P < 0.001) decrease in glomerular filtration rate, urine flow increased sixfold (P < 0.01) and urine sodium excretion increased sevenfold (P < 0.05), whereas urine osmolality decreased (P < 0.001). At the same time plasma antidiuretic hormone decreased from 7.5 ± 1.1 to 3.8 ± 0.4 pg mL^?1 (P = 0.01). After injection of desmopressin urine flow was completely restored, whereas urine osmolality and sodium excretion were only partially normalized. Since tubular conservation of water and fractional water reabsorption decreased during hypothermia, the diuresis must have resulted from an augmented loss of water. This is further supported by the fact that osmolal excretion was not influenced either by hypothermia or by desmopressin. It is concluded that the diuresis in consequence to hypothermia is due both to a decrease in the release of ADH and to a reduction of renal medullary hypertonicity.     

Isotonic and hypertonic sodium loading in supine humans

The hypothesis that hypertonic saline infusion induces a greater natriuresis than infusion of the same amount of sodium as isotonic saline was tested in 8 supine subjects on fixed sodium intake of 150 mmol NaCl day^–1. Sodium loads equivalent to the amount of sodium contained in 10% of measured extracellular volume were administered intravenously over 90 min either as isotonic saline or as hypertonic saline (850 mmol L^–1). A third series without saline infusion served as time control. Experiments lasted 8 h. Water balance and sodium loads were maintained by replacing the excreted amounts every hour. Plasma sodium concentrations only increased following hypertonic saline infusion (by 2.7 ± 0.3 mmol L^–1). Oncotic pressure decreased significantly more with isotonic saline (4.1 ± 0.3 mmHg) than with hypertonic saline (3.2 ± 0.2 mmHg), indicating that isotonic saline induced a stronger volumetric stimulus. Renal sodium excretion increased more than a factor of four with isotonic and hypertonic saline but also increased during time control (factor of three). Cumulated sodium excretions following isotonic (131 ± 13 mmol) and hypertonic saline (123 ± 10 mmol) were statistically identical exceeding that of time control (81 ± 9 mmol). Plasma angiotensin II decreased in all series but plasma ANP concentrations and urinary excretion rates of endothelin-1 remained unchanged. In conclusion, hypertonic saline did not produce excess natriuresis. However, as the two loading procedures induced similar natriureses during different volumetric stimuli, part of the natriuresis elicited by hypertonic saline could be mediated by stimulation of osmoreceptors involved in renal sodium excretion. The supine position does not provide stable time control conditions with regard to renal excretory function.     

The novel non-peptide selective endothelin A receptor antagonist LU 135 252 protects against myocardial ischaemic and reperfusion injury in the pig

The aim of the study was to investigate the efficacy of the novel non-peptide selective endothelin A (ET_A) receptor antagonist LU 135 252 to limit the extent of myocardial ischaemic and reperfusion injury. Administration of LU 135 252 (1 and 5 mg kg^–1 i.v.) to anaesthetised pigs reduced mean arterial pressure (MAP) from 91 ± 4 to 79 ± 3 mmHg (P < 0.05) and 96 ± 3–82 ± 3 mmHg (P < 0.01), respectively. Heart rate, coronary blood flow and coronary vascular resistance were not affected by LU 135 252. The infarct size induced by 45-min ligation of the left anterior descending coronary artery (LAD) followed by 4-h reperfusion in pigs was 81 ± 5% of the area at risk in control animals given vehicle (n = 8). In pigs receiving 1 mg kg^–1 (n = 6) or 5 mg kg^–1 (n = 8) of LU 135 252 i.v. 20 min before ischaemia the infarct size was reduced to 64 ± 3% (P < 0.05) and 35 ± 4% (P < 0.001), respectively, of the area at risk. During the reperfusion period there was a non-significant trend towards a higher coronary blood flow and a lower coronary vascular resistance in the groups given LU 135 252 compared to controls. Myocardial overflow of ET-like immunoreactivity was increased during the reperfusion period but it was not affected by administration of LU 135 252. It is concluded that administration of the selective ET_A receptor antagonist LU 135 252 effectively protects the myocardium from ischaemia/reperfusion injury, indicating that the ET_A receptor subtype is involved in the development of ischaemia/reperfusion injury.     

K+ as a vasodilator in resting human muscle: implications for exercise hyperaemia

Aim: Potassium (K⁺) released from contracting skeletal muscle is considered a vasodilatory agent. This concept is mainly based on experiments infusing non‐physiological doses of K⁺. The aim of the present study was to investigate the role of K⁺ in blood flow regulation. Methods: We measured leg blood flow (LBF) and arterio‐venous (A‐V) O₂ difference in 13 subjects while infusing K⁺ into the femoral artery at a rate of 0.2, 0.4, 0.6 and 0.8 mmol min^?1. Results: The lowest dose increased the calculated femoral artery plasma K⁺ concentration by approx.1 mmol L^?1. Graded K⁺ infusions increased LBF from 0.39 ± 0.06 to 0.56 ± 0.13, 0.58 ± 0.17, 0.61 ± 0.11 and 0.71 ± 0.17 L min^?1, respectively, whereas the leg A‐V O₂ difference decreased from 74 ± 9 to 60 ± 12, 52 ± 11, 53 ± 9 and 45 ± 7 mL L^?1, respectively (P < 0.05). Mean arterial pressure was unchanged, indicating that the increase in LBF was associated with vasodilatation. The effect of K⁺ was totally inhibited by infusion (27 μmol min^?1) of Ba²⁺, an inhibitor of Kir2.1 channels. Simultaneous infusion of ATP and K⁺ evoked an increase in LBF equalled to the sum of their effects. Conclusions: Physiological infusions of K⁺ induce significant increases in resting LBF, which are completely blunted by inhibition of the Kir2.1 channels. The present findings in resting skeletal muscle suggest that K⁺ released from contracting muscle might be involved in exercise hyperaemia. However, the magnitude of increase in LBF observed with K⁺ infusion suggests that K⁺ only accounts for a limited fraction of the hyperaemic response to exercise.     

Change point in V˙CO2 during incremental exercise test: a new method for assessment of human exercise tolerance

The main purpose of this study was to present a new method to determine the level of power output (PO) at which V˙CO ₂ during incremental exercise test (IT) begins to rise non-linearly in relation to power output (PO) – the change point in V˙CO ₂ (CP-V˙CO ₂). Twenty-two healthy non-smoking men (mean ± SD: age 22.0 ± 0.9 years; body mass 74.5 ± 7.5 kg; height 181 ± 7 cm; V˙O _2max 3.753 ± 0.335 l min^–1) performed an IT on a cycloergometer. The IT started at a PO of 30 W, followed by gradual increases of 30 W every 3 min. Antecubital venous blood samples were taken at the end of each step and analysed for plasma lactate concentration [La]_pl, blood PO ₂, PCO ₂ [HCO₃^–]_b and [H⁺]_b. In the detection of the change-point V˙CO ₂ (CP-V˙CO ₂), a two-phase model was assumed for the ‘third-minute-data’ of each step of the test. In the first phase, a linear relationship between V˙CO ₂ and PO was assumed, whereas in the second, an additional increase in V˙CO ₂ was allowed, above the values expected from the linear model. The PO at which the first phase ends is called the change point in V˙CO ₂. The identification of the model consists of two steps: testing for the existence of the change point, and estimating its location. Both procedures are based on suitably normalized recursive residuals (see 32 . Eur J Appl Physiol 78 , 369–377). In the case of each of our subjects it was possible to detect the CP-V˙CO ₂ and the CP-V˙O ₂ as described in our model. The PO at the CP-V˙CO ₂ amounted to 134 ± 42 W. The CP- V˙O ₂ was detected at 136 ± 32 W, whereas the PO at the LT amounted to 128 ± 30 W and corresponded to 49 ± 11, 49 ± 8 and 47 ± 8.6% V˙O _2max, respectively, for the CP-V˙CO ₂, CP-V˙O ₂ and the LT. The [La]_pl at the CP-V˙CO ₂ (2.65 ± 0.76 mmol L^–1), at the CP-V˙O ₂ (2.53 ± 0.56 mmol L^–1) and at the LT (2.25 ± 0.49 mmol L^–1) were already significantly higher (P < 0.01, Students t-test) than the value reached at rest (1.86 ± 0.43 mmol L^–1). Our study illustrates that the CP-V˙CO ₂ and the CP-V˙O ₂ occur at a very similar power output as the LT. We therefore postulate that the CP-V˙CO ₂ and the CP-V˙O ₂ be applied as an additional criterion to assess human exercise tolerance.     

Density and functioning of human lymphocytic β-adrenergic receptors during prolonged physical exercise

In order to study the regulation of β-adrenergic receptor number and function in response to prolonged physical effort, lymphocytic β-adrenoceptor density (determined by (-)[¹²⁵I]iodocyanopindolol binding), lymphocytic basal and isoproterenol-stimulated cyclic AMP (cAMP) production and concentrations of plasma catecholamines were measured before and during 3 h running exercise in eight healthy volunteers. A significant (P < 0.01) increase of the lymphocytic β-adrenoceptor density from 45±4 to 81 ± 9 fmol mg^-1 protein (mean ± SEM) took place during the first hour of exercise. As the exercise was continued for up to 2.1–3 h, the receptor densities did not change significantly any more and remained elevated (72 ± 9 fmol mg^-1 protein) in comparison to the resting levels (P < 0.02). The isoproterenol-stimulated cAMP production of the lymphocytes increased during the first hour of running from 190 ± 36 to 269 ± 56 pmol mg^-1 protein (P < 0.01) and returned to the resting level at the end of the exercise (182 ± 38 pmol mg^-1 protein). The mean levels of plasma catecholamines increased ? sixfold during the first hour of exercise and remained elevated until the end of the running. This study demonstrates that the β-adrenergic receptor system is activated in lymphocytes during prolonged aerobic physical exercise. This activated state becomes, however, attenuated within 2–3 h of exercise as indicated by a diminishing ability of β-adrenoceptors to mediate catecholamine-induced cAMP production.     

Increased plasma concentrations of vasopressin,oxytocin, cortisol and the prostaglandin F2α metabolite during labour in the dog

Aim: This study investigated if the plasma vasopressin concentration increases during labour in the dog and whether the change in vasopressin correlates with that of oxytocin, 15‐ketodihydro‐PGF_2α and cortisol. Methods: Five beagle dogs each delivered three to seven puppies. Blood samples were taken from a catheter inserted into the cephalic vein during labour and by venepuncture during the other periods. Results: Vasopressin concentration increased from 2 ± 0 pmol L^?1 (anoestrus) to 26 ± 11 pmol L^?1 at the birth of the first puppy, remained high at the birth of the second puppy and then decreased. Oxytocin increased from 63 ± 5 pmol L^?1 (anoestrus) to 166 ± 19 pmol L^?1 at the birth of the first puppy and remained elevated throughout labour. The PGF_2α metabolite concentration increased from 0.2 ± 0.0 nmol L^?1 (anoestrus) to 66 ± 17 nmol L^?1 at the birth of the first puppy and remained elevated 1 h after the completion of parturition. The cortisol concentration increased from 49 ± 9 nmol L^?1 (anoestrus) to 242 ± 35 nmol L^?1 at the birth of the first puppy, remained high during the birth of the second puppy and then declined. Conclusions: The plasma level of vasopressin was strongly correlated with that of cortisol but less with that of the PGF_2α metabolite, and not significantly with the concentration of oxytocin. This indicates that the four hormones play different roles during labour in the dog.     

Myocardial interstitial noradrenaline monitoring during occlusion of inferior vena cava in cats

To investigate myocardial interstitial noradrenaline (NA) kinetics during activation of systemic sympathetic nerves, we applied a dialysis technique to the left ventricle of anaesthetised cats and monitored myocardial interstitial NA levels during 6-min occlusion of the inferior vena cava (IVC). Dialysis probes were implanted in the left ventricular wall, and dialysate NA levels as an index of myocardial interstitial NA levels, were measured with high-performance liquid chromatographic–electrochemical detection. During IVC occlusion, dialysate NA levels progressively increased from 110 ± 17 pmol L^?1 in the control and reached 620 ± 160 pmol L^?1 at 4–6 min of IVC occlusion. Local administration of ω-conotoxin GVIA at 10 μM decreased the control dialysate NA level to 35 ± 0.2 pmol L^?1. The IVC occlusion induced increase in dialysate NA was suppressed only at 0–2 min of IVC occlusion. Intravenous injection of ω-conotoxin GVIA (10 μg kg^?1) did not increase the dialysate NA levels during IVC occlusion. Local administration of desipramine at 100 μM increased the control dialysate NA level to 900 ± 73 pmol L^?1. The IVC occlusion induced progressive increase in dialysate NA was augmented at 2–6 min of IVC occlusion. These results suggest that the early increase in myocardial interstitial NA levels is mainly caused by neuronal release of NA from cardiac sympathetic nerve terminals, and that extraction from the circulation and neuronal NA uptake contribute to changes in myocardial interstitial NA levels after a delay of several minutes.     

Maximal voluntary hyperpnoea increases blood lactate concentration during exercise

Ventilatory work during heavy endurance exercise has not been thought to influence systemic lactate concentration. We evaluated the effect of maximal isocapnic volitional hyperpnoea upon arterialised venous blood lactate concentration ([lac⁻]_B) during leg cycling exercise at maximum lactate steady state (MLSS). Seven healthy males performed a lactate minimum test to estimate MLSS, which was then resolved using separate 30 min constant power tests (MLSS=207±8 W, mean ± SEM). Thereafter, a 30 min control trial at MLSS was performed. In a further experimental trial, the control trial was mimicked except that from 20 to 28 min maximal isocapnic volitional hyperpnoea was superimposed on exercise. Over 20–28 min minute ventilation, oxygen uptake, and heart rate during the control and experimental trials were 87.3±2.4 and 168.3±7.0 l min⁻¹ (P<0.01), the latter being comparable to that achieved in the maximal phase of the lactate minimum test (171.9±6.8 l min⁻¹), 3.46±0.20 and 3.83 ± 0.20 l min⁻¹ (P<0.01), and 158.5±2.7 and 166.8±2.7 beats min⁻¹ (P<0.05), respectively. From 20 to 30 min of the experimental trial [lac⁻]_B increased from 3.7±0.2 to 4.7±0.3 mmol l⁻¹ (P<0.05). The partial pressure of carbon dioxide in arterialised venous blood increased approximately 3 mmHg during volitional hyperpnoea, which may have attenuated the [lac⁻]_B increase. These results show that, during heavy exercise, respiratory muscle work may affect [lac⁻]_B. We speculate that the changes observed were related to the altered lactate turnover in respiratory muscles, locomotor muscles, or both.     

Role of adenosine in exercise‐induced human skeletal muscle vasodilatation

The role of adenosine in exercise‐induced human skeletal muscle vasodilatation remains unknown. We therefore evaluated the effect of theophylline‐induced adenosine receptor blockade in six subjects and the vasodilator potency of adenosine infused in the femoral artery of seven subjects. During one‐legged, knee‐extensor exercise at ～48% of peak power output, intravenous (i.v.) theophylline decreased (P < 0.003) femoral artery blood flow (F_aBF) by ～20%, i.e. from 3.6 ± 0.5 to 2.9 ± 0.5 L min^?1, and leg vascular conductance (VC) from 33.4 ± 9.1 to 27.7 ± 8.5 mL min^?1 mmHg^?1, whereas heart rate (HR), mean arterial pressure (MAP), leg oxygen uptake and lactate release remained unaltered (P = n.s.). Bolus injections of adenosine (2.5 mg) at rest rapidly increased (P < 0.05) F_aBF from 0.3 ± 0.03 L min^?1 to a 15‐fold peak elevation (P < 0.05) at 4.1 ± 0.5 L min^?1. Continuous infusion of adenosine at rest and during one‐legged exercise at ～62% of peak power output increased (P < 0.05) F_aBF dose‐dependently to level off (P = ns) at 8.3 ± 1.0 and 8.2 ± 1.4 L min^?1, respectively. One‐legged exercise alone increased (P < 0.05) F_aBF to 4.7 ± 1.7 L min^?1. Leg oxygen uptake was unaltered (P = n.s.) with adenosine infusion during both rest and exercise. The present findings demonstrate that endogenous adenosine controls at least ～20% of the hyperaemic response to submaximal exercise in skeletal muscle of humans. The results also clearly show that arterial infusion of exogenous adenosine has the potential to evoke a vasodilator response that mimics the increase in blood flow observed in response to exercise.