Substrate utilization in sea level residents during exercise in acute hypoxia and after 4 weeks of acclimatization to 4100 m

To investigate the effect of acclimatization to hypoxia on substrate utilization, eight sea level residents were studied during exercise at the same relative (rel) and absolute (abs) work rate as at sea level (SL), under acute (AH), and after 4 weeks exposure to 4100 m altitude (CH). Carbohydrate (CHO) and fat oxidation during exercise at SL were 2.0 ± 0.2 and 0.3 ± 0.0 g min^?1, respectively. At AH_abs and CH_abs CHO oxidation increased (P < 0.05) to 2.5 ± 0.2 and 2.3 ± 0.1 for CHO, and fat oxidation decreased (P < 0.05) to 0.2 ± 0.01 and 0.2 ± 0.01 g min^?1, respectively. Exercise in AH_rel and CH_rel did not cause a change in the relative CHO and fat oxidation compared with SL, the absolute rate of CHO oxidized being 1.7 ± 0.1 and 1.7 ± 0.02 g min^?1, respectively, and fat oxidation was 0.2 ± 0.02 g min^?1 in AC_rel and 0.3 ± 0.02 g min^?1 in CH_rel. In conclusion, substrate utilization is unaffected by AH and CH, when the work rate is matched to the same relative intensity as at SL.     

The influence of PaO2, pH and SaO2 on maximal oxygen uptake

Influence of arterial oxygen pressure (P_aO₂) and pH on haemoglobin saturation (S_aO₂) and in turn on O₂ uptake (VO ₂) was evaluated during ergometer rowing (156, 276 and 376 W; VO _2max, 5.0 L min^?1; n = 11). During low intensity exercise, neither pH nor S_aO₂ were affected significantly. In response to the higher work intensities, ventilations (V_E) of 129 ± 10 and 155 ± 8 L min^?1 enhanced the end tidal PO₂ (P_ETO₂) to the same extent (117 ± 2 mmHg), but P_aO₂ became reduced (from 102 ± 2 to 78 ± 2 and 81 ± 3 mmHg, respectively). As pH decreased during maximal exercise (7.14 ± 0.02 vs. 7.30 ± 0.02), S_aO₂ also became lower (92.9 ± 0.7 vs. 95.1 ± 0.1%) and arterial O₂ content (C_aO₂) was 202 ± 3 mL L^?1. An inspired O₂ fraction (F_IO₂) of 0.30 (n = 8) did not affect V_E, but increased P_ETO₂ and P_aO₂ to 175 ± 4 and 164 ± 5 mmHg and the P_ETO₂–P_aO₂ difference was reduced (21 ± 4 vs. 36 ± 4 mmHg). pH did not change when compared with normoxia and S_aO₂ remained within 1% of the level at rest in hyperoxia (99 ± 0.1%). Thus, C_aO₂ and VO _2max increased to 212 ± 3 mL L^?1 and 5.7 ± 0.2 L min^?1, respectively. The reduced P_aO₂ became of importance for S_aO₂ when a low pH inhibited the affinity of O₂ to haemoglobin. An increased F_IO₂ reduced the gradient over the alveolar-arterial membrane, maintained haemoglobin saturation despite the reduction in pH and resulted in increases of the arterial oxygen content and uptake.     

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.     

Cerebral oxygenation decreases during exercise in humans with beta‐adrenergic blockade

Aim: Beta‐blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. Methods: Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion with or without administration of the non‐selective beta‐blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near‐infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension derived from arterial to internal jugular venous concentration differences. Results: Arterial lactate and cardiac output increased to 15.3 ± 4.2 mm and 20.8 ± 1.5 L min^?1 respectively (mean ± SD). Frontal lobe oxygenation remained unaffected but the calculated cerebral mitochondrial oxygen tension decreased by 29 ± 7 mmHg (P < 0.05). Propranolol reduced resting heart rate (58 ± 6 vs. 69 ± 8 beats min^?1) and at exercise exhaustion, cardiac output (16.6 ± 3.6 L min^?1) and arterial lactate (9.4 ± 3.7 mm ) were attenuated with a reduction in exercise capacity from 239 ± 42 to 209 ± 31 W (all P < 0.05). Propranolol also attenuated the increase in cerebral blood flow velocity and frontal lobe oxygenation (P < 0.05) whereas the cerebral mitochondrial oxygen tension decreased to a similar degree as during control exercise (delta 28 ± 10 mmHg; P < 0.05). Conclusion: Propranolol attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity.     

Hyperoxia does not increase peak muscle oxygen uptake in small muscle group exercise

We examined the influence of hyperoxia on peak oxygen uptake (V˙O _2peak) and peripheral gas exchange during exercise with the quadriceps femoris muscle. Young, trained men (n=5) and women (n=3) performed single-leg knee-extension exercise at 70% and 100% of maximum while inspiring normal air (NOX) or 60% O₂ (HiOX). Blood was sampled from the femoral vein of the exercising limb and from the contralateral artery. In comparison with NOX, hyperoxic arterial O₂ tension (P_aO ₂) increased from 13.5 ± 0.3 (x ± SE) to 41.6 ± 0.3 kPa, O₂ saturation (S_aO ₂) from 98 ± 0.1 to 100 ± 0.1%, and O₂ concentration (C_aO ₂) from 177 ± 4 to 186 ± 4 mL L^–1 (all P < 0.01). Peak exercise femoral venous PO ₂ (P_vO ₂) was also higher in HiOX (3.68 ± 0.06 vs. 3.39 ± 0.7 kPa; P < 0.05), indicating a higher O₂ diffusion driving pressure. HiOX femoral venous O₂ saturation averaged 36.8 ± 2.0% as opposed to 33.4 ± 1.5% in NOX (P < 0.05) and O₂ concentration 63 ± 6 vs. 55 ± 4 mL L^–1 (P < 0.05). Peak exercise quadriceps blood flow (Q˙_leg), measured by the thermo-dilution technique, was lower in HiOX than in NOX, 6.4 ± 0.5 vs. 7.3 ± 0.9 L min^–1 (P < 0.05); mean arterial blood pressure at inguinal height was similar in NOX and HiOX at 144 and 142 mmHg, respectively. O₂ delivery to the limb (Q˙_leq times C_aO ₂) was not significantly different in HiOX and NOX. V˙O _2peak of the exercising limb averaged 890 mL min^–1 in NOX and 801 mL min^–1 in HiOX (n.s.) corresponding to 365 and 330 mL min^–1 per kg active muscle, respectively. The V˙O _2peak-to-P_vO ₂ ratio was lower (P < 0.05) in HiOX than in NOX suggesting a lower O₂ conductance. We conclude that the similar V˙O _2peak values despite higher O₂ driving pressure in HiOX indicates a peripheral limitation for V˙O _2peak. This may relate to saturation of the rate of O₂ turnover in the mitochondria during exercise with a small muscle group but can also be caused by tissue diffusion limitation related to lower O₂ conductance.     

Exercise-induced decreases in sarcoplasmic reticulum Ca2+–ATPase activity attenuated by high-resistance training

Muscle biopsies were performed on the vastus lateralis muscle prior to and during a high-resistance training (HRT) programme in order to examine the effects of hypertrophy on sarcoplasmic reticulum Ca²⁺ ATPase activity at rest and during exercise. In six male untrained volunteers (peak aerobic power, V˙O ₂ peak = 3.39 ± 0.13 L min^?1, mean ± SE), the resting Ca²⁺ ATPase activity (μmol min^?1 g wet wt^?1) at 0 (4.89 ± 0.20), 4 (5.62 ± 0.56), 7 (5.15 ± 0.41) and 12 (4.82 ± 0.11) weeks was unchanged by HRT. During cycle ergometer exercise, prior to training, Ca²⁺-ATPase was reduced (P < 0.05) by 14% during the initial 30 min at 58% VO ₂ peak and (P < 0.05) a further 19% during 30 min at 72% VO ₂ peak. Following 7 and 12 weeks of training, the decreases in SR Ca²⁺-ATPase were less pronounced (P < 0.05). These results indicate that muscle hypertrophy, although incapable of altering Ca²⁺-ATPase pump activity at rest, can attenuate the decrease observed in exercise by mechanism(s) as yet unknown.     

Cardiovascular and ventilatory responses to electrically induced cycling with complete epidural anaesthesia in humans

Cardiovascular and ventilatory responses to electrically induced dynamic exercise were investigated in eight healthy young males with afferent neural influence from the legs blocked by epidural anaesthesia (25 ml 2% lidocaine) at L3-L4. This caused cutaneous sensory anaesthesia below T8-T9 and complete paralysis of the legs. Cycling was performed for 22.7 ± 2.7 min (mean, SE) (fatigue) and oxygen uptake (Vo₂) increased to 1.90 ± 0.13 1 min^-1. Compared with voluntary exercise at the same Vo₂, increases in heart rate (HR) (135 ± 7 vs. 130 ± 9 beats min^-1) and cardiac output (16.9 ± 1.1 vs. 17.3 ± 0.9 1 min^-1) were similar, and ventilation (54 ± 5 vs. 45 ± 4 1 min^-1) was higher (P < 0.05). In contrast, the rise in mean arterial blood pressure during voluntary exercise (93 ± 4 (rest) to 119 ± 4 mmHg (exercise)) was not manifest during electrically induced exercise with epidural anaesthesia [93 ± 3 (rest) to 95 ± 5 mmHg (exercise)]. As there is ample evidence for similar cardiovascular and ventilatory responses to electrically induced and voluntary exercise (Strange et al. 1993), the present results support the fact that the neural input from working muscle is crucial for the normal blood pressure response to exercise. Other haemodynamic and/or humoral mechanisms must operate in a decisive manner in the control of HR, CO and VE during dynamic exercise with large muscle groups.     

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.     

Enhanced rates of muscle protein synthesis and elevated mTOR signalling following endurance exercise in human subjects

Aim: The major aim of this study was to determine the fractional rate of protein synthesis (FSR) during the early period of recovery after intensive aerobic exercise in the absence of nutritional supplementation. Methods: Sixteen male subjects performed one‐legged cycling exercise for 1 h at approx. 65–70% of their one‐legged maximal oxygen uptake. Using the stable isotope technique, the FSR in the vastus lateralis of both legs were determined during two periods, 0–90 min (n = 8) and 90–180 min (n = 8) after exercise. Biopsies were taken from both exercising and resting muscle before exercise, immediately after and following 90 or 180 min of recovery. Results: During the initial 90 min of recovery, FSR in the exercising muscle tended to be higher than in the resting muscle (1.57 ± 0.12 vs. 1.44 ± 0.07% 24 h^?1; P = 0.1) and was significantly higher during the period 90–180 min after exercise (1.74 ± 0.14 vs. 1.43 ± 0.12% 24 h^?1; P < 0.05). Exercise induced a 60% increase (P < 0.05) in phosphorylation of mTOR and a fivefold increase (P < 0.05) in Thr³⁸⁹ phosphorylation of p70S6 kinase as well as a 30% reduction (P < 0.05) in phosphorylation of eEF2. Phosphorylation of AMP‐activated protein kinase was enhanced by 40% (P < 0.05) after exercise, but no significant effect on phosphorylation of Akt, or eIF2Bε was observed immediately after exercise. Conclusion: These findings indicate that during the first 3 h of recovery after intensive endurance exercise FSR gradually increases. Moreover, a stimulation of the mTOR‐signalling pathway may be at least partially responsible for this elevated protein synthesis.     

Oral creatine supplementation decreases plasma markers of adenine nucleotide degradation during a 1‐h cycle test

We investigated the effect of oral creatine supplementation (20 g d^?1 for 7 days) on metabolism during a 1‐h cycling performance trial. Twenty endurance‐trained cyclists participated in this double‐blind placebo controlled study. Five days after familiarization with the exercise test, the subjects underwent a baseline muscle biopsy. Thereafter, a cannula was inserted into a forearm vein before performing the baseline maximal 1‐h cycle (test 1 (T1)). Blood samples were drawn at regular intervals during exercise and recovery. After creatine (Cr) loading, the muscle biopsy, 1‐h cycling test (test 2 (T2)) and blood sampling were repeated. Resting muscle total creatine (TCr), measured by high performance liquid chromatography, was increased (P < 0.001) in the creatine group from 123.0 ± 3.8 ? 159.8 ± 7.9 mmol kg^?1 dry wt, but was unchanged in the placebo group (126.7 ± 4.7 ? 127.5 ± 3.6 mmol kg^?1 dry wt). The extent of Cr loading was unrelated to baseline Cr levels (r=0.33, not significant). Supplementation did not significantly improve exercise performance (Cr group: 39.1 ± 0.9 vs. 39.8 ± 0.8 km and placebo group: 39.3 ± 0.8 vs. 39.2 ± 1.1 km) or change plasma lactate concentrations. Plasma concentrations of ammonia (NH₃) (P < 0.05) and hypoxanthine (Hx) (P < 0.01) were lower in the Cr group from T1 to T2. Our results indicate that Cr supplementation alters the metabolic response during sustained high‐intensity submaximal exercise. Plasma data suggest that nett intramuscular adenine nucleotide degradation may be decreased in the presence of enhanced intramuscular TCr concentration even during submaximal exercise.     

Comparison of gas exchange data using the Aquatrainer® system and the facemask with Cosmed K4b2 during exercise in healthy subjects

The aim of this study was to determine the level of agreement between the new Aquatrainer^® system and the facemask in the assessment of submaximal and maximal cardiopulmonary responses during exercise performed on ergocycle. Twenty-six physically active healthy subjects (mean age: 41 ± 14 years) performed a submaximal constant work test followed by maximal incremental exercise test on ergocycle, one with cardiopulmonary responses measured using the Cosmed K4b2 facemask, the other using the Cosmed K4b2 Aquatrainer^®. Using the Aquatrainer^®, the gas exchange variables at 100 W were significantly lower for VO₂ (1,483 ± 203 vs. 1,876 ± 204 ml min^?1, P < 0.0001), VCO₂ (1,442 ± 263 vs. 1,749 ± 231 ml min^-1, P < 0.0001), VE (38 ± 5 vs. 44 ± 6 l min^?1, P < 0.0001), and VT (1.92 ± 0.47 vs. 2.18 ± 0.41 l, P < 0.0001) relative to facemask. The bias ±95% limits of agreement (LOA) for VO₂ was 393 ± 507 ml min^?1 for the submaximal constant work test at 100 W and 495 ± 727 ml min^?1 for VO_2max. At maximal intensity, cardiopulmonary responses measured with the Aquatrainer^® system were significantly lower for: VO₂ (2,799 ± 751 vs. 3,294 ± 821 ml min^?1, P < 0.0001), VCO₂ (3,426 ± 836 vs. 3,641 ± 946 ml min^?1, P = 0.012), VE (98 ± 21 vs. 108 ± 26 l min^?1, P = 0.0009) relative to facemask. A non-constant measurement error [interaction effect: (facemask or aquatrainer) × power] was noted from 60 to 270 W for VO₂ (ml min^?1), VCO₂ (ml min^?1), ventilation (l min^?1) (P < 0.0001) and VT (l, P = 0.0001). Additional studies are required to detect the main sources of error that could be physical and/or physiological in nature. Due to the significant measurement error, the new Aquatrainer^® system should be used with extreme caution in filed testing conditions of swimmers.     

Effect of drink pattern and solar radiation on thermoregulation and fluid balance during exercise in chronically heat acclimatized children

The purposes of this study were to examine the thermoregulatory and body fluid balance responses in chronically heat acclimatized children, i.e., indigenous to a tropical climate, during exercise in four outdoor conditions and the effects of dehydration on their thermoregulatory response. Nine children (age = 13.3 ± 1.9 yr, VO₂max = 45.5 ± 9.2 ml · kg^?1 · min^?1) cycled at 60% VO₂max each under four conditions: sun exposure voluntary drinking (SuVD), sun exposure forced drinking (SuFD), shaded voluntary drinking (ShVD), and shaded forced drinking (ShFD). Exercise sessions consisted of four 20-min exercise bouts alternating with 25-min rest periods. Globe temperature and the WBGT index were higher during SuVD and SuFD compared to ShVD and ShFD (P < 0.05). The change in rectal temperature, metabolic heat production, and heat storage did not differ among the conditions. Total water intake (% IBW) was higher during SuFD (4.1 ± 0.01) and ShFD (3.7 ± 0.1) compared to SuVD (2.1 ± 0.1) and ShVD (1.0 ± 0.1) and during SuVD compared to ShVD (P < 0.05). Sweating rate (L · hr^?1) was higher during SuFD (0.7 ± 0.1) and ShFD (0.6 ± 0.1) compared to SuVD (0.5 ± 0.1) and ShVD (0.4 ± 0.1) (P < 0.05). Total fluid loss did not differ among conditions (SuVD = 1.7 ± 0.4; SuFD = 1.5 ± 0.4; ShVD = 2.1 ± 0.2; ShFD = 1.3 ± 0.3). Results indicate that when exercising in a tropical climate, chronically heat acclimatized children demonstrate mild voluntary dehydration and adequate heat dissipation. © 1995 Wiley-Liss, Inc.     

Global cerebral blood flow during infusion of adenosine in humans: assessment by magnetic resonance imaging and positron emission tomography

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 μg kg^?1 min^?1), adenosine has shown to have an analgesic effect. This study was undertaken to investigate whether a low dose, causing tolerable symptoms of peripheral vasodilation affects the global cerebral blood flow (CBF). In nine healthy volunteers CBF measurements were made using axial magnetic resonance (MR) phase images of the internal carotid and vertebral arteries at the level of C2–3. Quantitative assessment of CBF was also obtained with positron emission tomography (PET) technique, using intravenous bolus []> ¹⁵O]butanol as tracer in four of the subject at another occasion. During normoventilation (5.4 ± 0.2 kPa, mean ± s.e.m.), the cerebral blood flow measured by magnetic resonance imaging technique, as the sum of the flows in both carotid and vertebral arteries, was 863 ± 66 mL min^?1, equivalent to about 64 ± 5 mL 100 g^?1 min^?1. The cerebral blood flow measured by positron emmission tomography technique, was 59 ± 4 mL 100 g^?1 min^?1. All subjects had a normal CO₂ reactivity. When adenosine was infused (84 ± 7 μg kg^?1 min^?1) the cerebral blood flow, measured by magnetic resonance imaging was 60 ± 5 mL 100 g^?1 min^?1. The end tidal CO₂ level was slightly lower (0.2 ± 0.1 kPa) during adenosine infusion than during normoventilation. In the subgroup there was no difference in cerebral blood flow as measured by magnetic resonance imaging or positron emission tomography. In conclusion, adenosine infusion at tolerable doses in healthy volunteers does not affect global cerebral blood flow in unanaesthetized humans.     

Treadmill but not wheel running improves fatigue resistance of isolated extensor digitorum longus muscle in mice

Aim: The present study is the first to compare the physiological impact of either forced treadmill or voluntary wheel running exercise on hindlimb muscle in mice. Methods: Male C57BL/6 mice were subjected to either 6 weeks of forced treadmill or voluntary wheel running exercise. Mice in the treadmill running exercise group (TRE; n = 8) ran 1.9 km day^?1 at a speed of 16 m min^?1 against an uphill incline of 11 °. In the running wheel exercise group (RWE; n = 8) animals ran 8.8 ± 0.2 km per day (average speed 42 ± 2 m min^?1). After the experimental period, animals were killed and mechanical performance and oxygen consumption of isolated extensor digitorum longus (EDL) muscle were determined during serial electrical stimulation at 0.5, 1 and 2 Hz. Results: Steady‐state half‐width time (HWT) of twitch contraction at 0.5 Hz was significantly shorter in TRE and RWE than controls (CON) (41.3 ± 0.2, 41.3 ± 0.1 and 44.3 ± 0.1 s respectively; P < 0.05). The rate of fatigue development and HWT lengthening at 2 Hz was the same in RWE and CON but lower in TRE (1.2‐fold and twofold respectively; P < 0.05). EDL oxygen consumption, mitochondrial content and myosin heavy chain (MyHC) composition were not different between the groups. Conclusion: These results indicate that both exercise modalities have an effect on a hindlimb fast‐twitch muscle in mice, with the greatest impact seen with forced treadmill running.     

Reducing plasma free fatty acids by acipimox improves glucose tolerance in high‐fat fed mice

To study whether free fatty acids (FFAs) contribute to glucose intolerance in high‐fat fed mice, the derivative of nicotinic acid, acipimox, which inhibits lipolysis, was administered intraperitoneally (50 mg kg^?1) to C57BL/6J mice which had been on a high‐fat diet for 3 months. Four hours after administration of acipimox, plasma FFA levels were reduced to 0.46 ± 0.06 mmol L^?1 compared with 0.88 ± 0.10 mmol L^?1 in controls (P < 0.001). At this point, the glucose elimination rate after an intravenous glucose load (1 g kg^?1) was markedly improved. Thus, the elimination constant (K_G) for the glucose disposal between 1 and 50 min after the glucose challenge was increased from 0.54 ± 0.01% min^?1 in controls to 0.66 ± 0.01% min^?1 by acipimox (P < 0.001). In contrast, the acute insulin response to glucose (1–5 min) was not significantly different between the groups, although the area under the insulin for the entire 50‐min period after glucose administration was significantly reduced by acipimox from 32.1 ± 2.9 to 23.9 ± 1.2 nmol L^?1 × 50 min (P=0.036). This, however, was mainly because of lower insulin levels at 20 and 50 min because of the lowered glucose levels. In contrast, administration of acipimox to mice fed a normal diet did not affect plasma levels of FFA or the glucose elimination or insulin levels after the glucose load. It is concluded that reducing FFA levels by acipimox in glucose intolerant high‐fat fed mice improves glucose tolerance mainly by improving insulin sensitivity making the ambient islet function adequate, suggesting that increased FFA levels are of pathophysiological importance in this model of glucose intolerance.     

Long-lasting coronary vasoconstrictor effects and myocardial uptake of endothelin-1 in humans

The effect of intravenous administration of the endothelium-derived vasoconstrictor peptide endothelin-1 (ET-1 0.2, 1 and 8 pmol kg^?1 min^?1) on coronary blood flow in relation to plasma ET-1 as well as blood lactate and glucose levels were investigated in six healthy volunteers. Coronary sinus blood flow was measured by thermodilution. Administration of ET-1 elevated arterial plasma ET 35-fold, dose-dependently increased mean arterial blood pressure from 95±5 mmHg to 110±6 mmHg (P<0.01) and reduced heart rate from 64±4 beats min^?1 to 58±4 beats min^?1 (P<0.05) at 8 pmol kg^?1 min^?1. Coronary sinus blood flow was reduced maximally by 23±4% (P<0.01) and coronary vascular resistance increased by 48±11% (P<0.01). Coronary sinus oxygen saturation decreased from 35±1% to 22±2% at 2 min after the infusion (P<0.01). A coronary constrictor response was observed at a 4-fold elevation in plasma ET. The reduction in coronary sinus blood flow lasted 20 min and coronary sinus oxygen saturation was still reduced 60 min after the infusion. Myocardial oxygen uptake or arterial oxygen saturation were not affected by ET-1. Myocardial lactate net uptake decreased by 40% whereas glucose uptake was unaffected. At the highest infusion rate there was a net removal of plasma ET by 24±3% over the myocardium (P<0.05). The results show that ET-1 induces long-lasting reduction in coronary sinus blood flow via a direct coronary vasoconstrictor effect in healthy humans observable at a 4-fold elevation in plasma ET-1. Furthermore, there is a net removal of circulating ET-1 by the myocardium.     

Effect of endurance training on muscle microvascular filtration capacity and vascular bed morphometry in the elderly

Aim: Exercise training is a strong stimulus for vascular remodelling and could restore age‐induced vascular alterations. The purpose of the study was to test the hypothesis that an increase in vascular bed filtration capacity would corroborate microvascular adaptation with training. Methods: We quantified (1) microvascularization from vastus lateralis muscle biopsy to measure the capillary to fibre interface (LC/PF) and (2) the microvascular filtration capacity (K_f) in lower limbs through a venous congestion plethysmography procedure. Twelve healthy older subjects (74 ± 4 years) were submitted to a 14‐week training programme during which lower‐limbs were trained for endurance exercise. Results: The training programme induced a significant increase in the aerobic exercise capacity of lower limbs (+11%Vo _2peak; P < 0.05; +28% Citrate Synthase Activity; P < 0.01). K_f was largely increased (4.3 ± 0.9 10^?3 mL min^?1 mmHg^?1 100 mL^?1 post‐training vs. 2.4 ± 0.8 pre‐training, mean ± SD; P < 0.05) and microvascularization developed as shown by the rise in LC/PF (0.29 ± 0.06 post‐ vs. 0.23 ± 0.06 pre‐training; P < 0.05). Furthermore, K_f and LC/PF were correlated (r = 0.65, P < 0.05). Conclusion: These results demonstrated the microvascular adaptation to endurance training in the elderly. The increase in K_f with endurance training was probably related to a greater surface of exchange with an increased microvessel/fibre interface area. We conclude that measurement of the microvascular filtration rate reflects the change in the muscle exchange area and is influenced by exercise training.     

Effects of adenosine on ex vivo filtragometry platelet aggregation in relation to plasma levels

The aim of the present study was to investigate the concentration effect of adenosine on unstimulated platelet aggregation in humans. Adenosine infusion was given intravenously to 12 volunteers in the antecubital vein with infusion rates increasing from 20 to 100 μg kg^?1 min^?1. Filtragometry measurements were obtained from the contralateral antecubital vein before and during 100 μg kg^?1 min^?1 or during maximal tolerable infusion rate. In another set of experiments with 10 volunteers, basal filtragometry measurements were obtained before and after infusion of various concentrations of adenosine into the filtragometer test unit. With intravenous infusion aggregation time tended to increase from 333±42 to 418±8 s (mean±SEM) and increased the venous plasma adenosine concentration from 0.42±0.09 μM to 1.52±0.38 μM . Adenosine infusion into the filtragometer tubing system dose-dependently inhibited aggregation (P<0.05). Adenosine was rapidly eliminated with a half-life of adenosine in the filtragometry tubing system calculated to be about 6 s. These data extend our knowledge from an in vitroto an ex vivo situation that adenosine dose-dependently has a platelet antiaggregatory effect.     

Cardiac output but not stroke volume is similar in a Wingate and \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} test in young men

Wingate test (WT) training programmes lasting 2?C3?weeks lead to improved peak oxygen consumption. If a single 30?s WT was capable of significantly increasing stroke volume and cardiac output, the increase in peak oxygen consumption could possibly be explained by improved oxygen delivery. Thus, we investigated whether a single WT increases stroke volume and cardiac output to similar levels than those obtained at peak exercise during a graded cycling exercise test (GXT) to exhaustion. Fifteen healthy young men (peak oxygen consumption 45.0?±?5.3?ml?kg^?1?min^?1) performed one WT and one GXT on separate days in randomised order. During the tests, we estimated cardiac output using inert gas rebreathing (nitrous oxide and sulphur hexafluoride) and subsequently calculated stroke volume. We found that cardiac output was similar (18.2?±?3.3 vs. 17.9?±?2.6?l?min^?1; P?=?0.744), stroke volume was higher (127?±?37 vs. 94?±?15?ml; P?<?0.001), and heart rate was lower (149?±?26 vs. 190?±?12 beats?min^?1; P?<?0.001) at the end (27?±?2?s) of a WT as compared to peak exercise during a GXT. Our results suggest that a single WT produces a haemodynamic response which is characterised by similar cardiac output, higher stroke volume and lower heart rate as compared to peak exercise during a GXT.     

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.