Middle cerebral artery blood velocity,arterial diameter and muscle sympathetic nerve activity during post-exercise muscle ischaemia

During exercise the transcranial Doppler determined mean blood velocity (V_mean) increases in the middle cerebral artery (MCA) and reflects cerebral blood flow when the diameter at the site of investigation remains constant. Sympathetic activation could induce MCA vasoconstriction and in turn elevate V_mean at an unchanged cerebral blood flow. In 12 volunteers we evaluated whether V_mean relates to muscle sympathetic nerve activity (MSNA) in the peroneal nerve during rhythmic handgrip and post-exercise muscle ischaemia (PEMI). The luminal diameter of the dorsalis pedis artery (AD) was taken to reflect the MSNA influence on a peripheral artery. Rhythmic handgrip increased heart rate (HR) from 74 ± 20 to 92 ± 21 beats min^?1 and mean arterial pressure (MAP) from 87 ± 7 to 105 ± 9 mmHg (mean ± SD; P < 0.05). During PEMI, HR returned to pre-exercise levels while MAP remained elevated (101 ± 9 mmHg). During handgrip contralateral MCA V_mean increased from 65 ± 10 to 75 ± 13 cm s^?1 and this was more than on the ipsilateral side (from 63 ± 10 to 68 ± 10 cm s^?1; P < 0.05). On both sides of the brain V_mean returned to baseline during PEMI. MSNA did not increase significantly during handgrip (from 56 ± 24 to 116 ± 39 units) but the elevation became statistically significant during PEMI (135 ± 86 units, P < 0.05), while AD did not change. Taken together, during exercise and PEMI, V_mean changed independent of an elevation of MSNA by more than 140% and the dorsalis pedis artery diameter was stable. The results provide no evidence for a vasoconstrictive influence of sympathetic nerve activity on medium size arteries of the limbs and the brain during rhythmic handgrip and post-exercise muscle ischaemia.     

Enhanced cerebral CO2 reactivity during strenuous exercise in man

Light and moderate exercise elevates the regional cerebral blood flow by ~20% as determined by ultrasound Doppler sonography (middle cerebral artery mean flow velocity; MCA V _mean). However, strenuous exercise, especially in the heat, appears to reduce MCA V _mean more than can be accounted for by the reduction in the arterial CO₂ tension (P _aCO₂). This study evaluated whether the apparently large reduction in MCA V _mean at the end of exhaustive exercise relates to an enhanced cerebrovascular CO₂ reactivity. The CO₂ reactivity was evaluated in six young healthy male subjects by the administration of CO₂ as well as by voluntary hypo- and hyperventilation at rest and during exercise with and without hyperthermia. At rest, P _aCO₂ was 5.1±0.2 kPa (mean ± SEM) and MCA V _mean 50.7±3.8 cm s⁻¹ and the relationship between MCA V _mean and P _aCO₂ was linear (double-log slope 1.1±0.1). However, the relationship became curvilinear during exercise (slope 1.8±0.1; P<0.01 vs. rest) and during exercise with hyperthermia (slope 2.3±0.3; P<0.05 vs. control exercise). Accordingly, the cerebral CO₂ reactivity increased from 30.5±2.7% kPa⁻¹ at rest to 61.4±10.1% kPa⁻¹ during exercise with hyperthermia (P<0.05). At exhaustion P _aCO₂ decreased 1.1±0.2 kPa during exercise with hyperthermia, which, with the determined cerebral CO₂ reactivity, accounted for the 28±10% decrease in MCA V _mean. The results suggest that during exercise changes in cerebral blood flow are dominated by the arterial carbon dioxide tension.     

Middle cerebral artery blood velocity and plasma catecholamines during exercise

During dynamic exercise, mean blood velocity (V_mean) in the middle cerebral artery (MCA) demonstrates a graded increase to work rate and reflects regional cerebral blood flow. At a high work rate, however, vasoactive levels of plasma catecholamines could mediate vasoconstriction of the MCA and thereby elevate V_mean at a given volume flow. To evaluate transcranial Doppler-determined V_mean at high plasma catecholamine levels, seven elite cyclists performed a maximal performance test on a bicycle ergometer. Results were compared with those elicited during five incremental exercise bouts and during rhythmic handgrip when plasma catecholamines are low. During rhythmic handgrip the V_mean was elevated by 21±3% (mean±SE), which was not statistically different from that established during moderate cycling. However, at the highest submaximal and maximal work intensities on the bicycle ergometer, V_mean increased by 31±3% and 48±4%, respectively, and this was significantly higher compared to handgrip (P<0.05). During maximal cycling, plasma adrenaline increased from 0.21±0.04 nmol L^-1 at rest to 4.18±1.46 nmol L^-1, and noradrenaline increased from 0.79±0.08 to 12.70±1.79 nmol L^-1. These levels were 12- to 16-fold higher than those during rhythmic handgrip (adrenaline: 0.34±0.03 nmol L^-1; noradrenaline: 0.78±0.05 nmol L^-1). The increase in V_mean during intense ergometer cycling conforms to some middle cerebral artery constriction elicited by plasma catecholamines. Such an influence is unlikely during rhythmic handgrip compared with low intensity cycling.     

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.     

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.     

Middle cerebral artery blood velocity during exercise with beta-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 beta-1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocaine; 8 mL; n=8) affects the attenuated exercise - MCA V(mean following cardio-selective beta-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 delta MCA 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 beta-1 blockade induced attenuation in delta MCA 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.     

Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus femoris blood oxygenation (near-infrared spectroscopy) and systemic blood flow (cardiac output from model flow analysis of the arterial pressure wave) as induced by dynamic exercise of large (cycling) vs. small muscle groups (rhythmic handgrip) before and after cardioselective β₁ adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.). During rhythmic handgrip, the increments in systemic haemodynamic variables as in middle cerebral artery mean blood velocity were not influenced significantly by metoprolol. In contrast, during cycling (e.g. 113 W), metoprolol reduced the increase in cardiac output (222 ± 13 vs. 260 ± 16%), heart rate (114 ± 3 vs. 135 ± 7 beats min^?1) and mean arterial pressure (103 ± 3 vs.112 ± 4 mmHg), and the increase in cerebral artery mean blood velocity also became lower (from 59 ± 3 to 66 ± 3 vs. 60 ± 2 to 72 ± 3 cm s^?1; P < 0.05). Likewise, during cycling with metoprolol, oxyhaemoglobin in the rectus femoris muscle became reduced (compared to rest; ?4.8 ± 1.8 vs. 1.2 ± 1.7 μmol L^?1, P < 0.05). Neither during rhythmic handgrip nor during cycling was the arterial carbon dioxide tension affected significantly by metoprolol. The results suggest that as for the muscle blood flow, the cerebral circulation is also affected by a reduced cardiac output during exercise with a large muscle mass.     

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.     

Evaluation of renal oxygenation change under the influence of carbogen breathing using a dynamic R2, R2′ and R2* quantification approach

The purpose of this study is to demonstrate the feasibility of dynamic renal R₂/R₂′/R₂* measurements based on a method, denoted psMASE‐ME, in which a periodic 180° pulse‐shifting multi‐echo asymmetric spin echo (psMASE) sequence, combined with a moving estimation (ME) strategy, is adopted. Following approval by the institutional animal care and use committee, a block design of respiratory challenge with interleaved air and carbogen (97% O₂, 3% CO₂) breathing was employed in nine rabbits. Parametrical R₂/R₂′/R₂* maps were computed and average R₂/R₂′/R₂* values were measured in regions of interest in the renal medulla and cortex. Bland–Altman plots showed good agreement between the proposed method and reference standards of multi‐echo spin echo and multi‐echo gradient echo sequences. Renal R₂, R₂′ and R₂* decreased significantly from 16.2 ± 4.4 s^?1, 9.8 ± 5.2 s^?1 and 25.9 ± 5.0 s^?1 to 14.9 ± 4.4 s^?1 (p < 0.05), 8.5 ± 4.1 s^?1 (p < 0.05) and 23.4 ± 4.8 s^?1 (p < 0.05) in the cortex when switching the gas mixture from room air to carbogen. In the renal medulla, R₂, R₂′ and R₂* also decreased significantly from 12.9 ± 4.7 s^?1, 15.1 ± 5.8 s^?1 and 27.9 ± 5.3 s^?1 to 11.8 ± 4.5 s^?1 (p < 0.05), 14.2 ± 4.2 s^?1 (p < 0.05) and 25.8 ± 5.1 s^?1 (p < 0.05). No statistically significant differences in relative R₂, R₂′ and R₂* changes were observed between the cortex and medulla (p = 0.72 for R₂, p = 0.39 for R₂′ and p = 0.61 for R₂*). The psMASE‐ME method for dynamic renal R₂/R₂′/R₂* measurements, together with the respiratory challenge, has potential use in the evaluation of renal oxygenation in many renal diseases     

Attenuated relationship between cardiac output and oxygen uptake during high-intensity exercise

Aim: Recent findings have challenged the belief that the cardiac output (CO) and oxygen consumption (VO₂) relationship is linear from rest to maximal exercise. The purpose of this study was to determine the CO and stroke volume (SV) response to a range of exercise intensities, 40–100% of VO_2max, during cycling. Methods: Ten well‐trained cyclists performed a series of discontinuous exercise bouts to determine the CO and SV vs. VO₂ responses. Results: The rate of increase in CO, relative to VO₂, during exercise from 40 to 70% of VO_2max was 4.4 ± 1.4 L L^?1. During exercise at 70–100% of VO_2max, the rate of increase in CO was reduced to 2.1 ± 0.9 L L^?1 (P = 0.01). Stroke volume during exercise at 80–100% of VO_2max was reduced by 7% when compared to exercise at 50–70% of VO_2max (134 ± 5 vs. 143 ± 5 mL per beat, P = 0.02). Whole body arterial‐venous O₂ difference increased significantly as intensity increased. Conclusion: The observation that the rate of increase in CO is reduced as exercise intensity increases suggests that cardiovascular performance displays signs of compromised function before maximal VO₂ is reached.     

Feasibility and repeatability of localized 31P‐MRS four‐angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T

Phosphorus (³¹P) MRS, combined with saturation transfer (ST), provides non‐invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T₁^app measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four‐angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra‐high‐field MR system, to accelerate the measurement of both P_i‐to‐ATP and PCr‐to‐ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth‐resolved surface coil MRS (DRESS)‐localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, P_i‐to‐ATP and PCr‐to‐ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS‐localized FAST method. The repeatability of PCr‐to‐ATP and P_i‐to‐ATP exchange rate constants, determined by the slab‐selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr‐to‐ATP metabolic flux decreased (from F_CK = 8.21 ± 1.15 mM s^?1 to F_CK = 3.86 ± 1.38 mM s^?1) and the P_i‐to‐ATP flux increased (from F_ATP = 0.43 ± 0.14 mM s^?1 to F_ATP = 0.74 ± 0.13 mM s^?1). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS‐localized FAST method at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

The postural reduction in middle cerebral artery blood velocity is not explained by PaCO2

In the normocapnic range, middle cerebral artery mean velocity (MCA V _mean) changes ∼ 3.5% per mmHg carbon-dioxide tension in arterial blood (PaCO₂) and a decrease in PaCO₂ will reduce the cerebral blood flow by vasoconstriction (the CO₂ reactivity of the brain). When standing up MCA V _mean and the end-tidal carbon-dioxide tension (PETCO₂) decrease, suggesting that PaCO₂ contributes to the reduction in MCA V _mean. In a fixed body position, PETCO₂ tracks changes in the PaCO₂ but when assuming the upright position, cardiac output decreases and its distribution over the lung changes, while ventilation increases suggesting that PETCO₂ decreases more than PaCO₂. This study evaluated whether the postural reduction in PaCO₂ accounts for the postural decline in MCA V _mean. From the supine to the upright position, PETCO₂, PaCO₂, MCA V _mean, and the near-infrared spectrophotometry determined cerebral tissue oxygenation (CO₂Hb) were followed in seven subjects. When standing up, MCA V _mean (from 65.3±3.8 to 54.6±3.3 cm s⁻¹ ; mean ± SEM; P<0.05) and cO₂Hb (−7.2±2.2 μmol l⁻¹ ; P<0.05) decreased. At the same time, the ratio increased 49±14% (P<0.05) with the postural reduction in PETCO₂ overestimating the decline in PaCO₂ (−4.8±0.9 mmHg vs. −3.0±1.1 mmHg; P<0.05). When assuming the upright position, the postural decrease in MCA V _mean seems to be explained by the reduction in PETCO₂ but the small decrease in PaCO₂ makes it unlikely that the postural decrease in MCA V _mean can be accounted for by the cerebral CO₂ reactivity alone.     

Altered basal and adenosine-mediated protein flux from coronary arterioles isolated from exercise-trained pigs

Solute flux per unit surface area and concentration gradient, (J_S/SΔC), was quantified in arterioles isolated from hearts of sedentary (SED) and exercise-trained (EX) female Yucatan Miniature Swine. Apparent permeability (P_S) was assessed from measures of J_S/SΔC for two proteins, α-lactalbumin (α-lact) and porcine serum albumin (PSA), under basal conditions and following 5 min suffusion with 10^?5M adenosine (ADO). Both proteins were labelled with the fluorescent dye tetramethyl rhodamine isothiocyanate. Basal P_s to α-lact differed with exercise training ((P^α-lact_s)_SED=5.2±1.8 (median±median absolute deviation (MAD), n=9 pigs) versus (P^α-lact_s)_EX=7.4±1.1×10^?7 cm s^?1, n=9, P<0.05). For the larger protein PSA, basal P_s did not change with training ((P^PSA_s)_SED=5.0±1.6, N=11 vs. (P^PSA_s)_EX=4.1±1.2×10^?7 cm s^?1, N=11). Suffusion of the arterioles (33±4 μm diameter, n=18 vessels) from SED hearts (n=14) with 10^?5M ADO decreased P^α-lact_s 15±8% relative to control and was without effect on P^PSA_s. By contrast, in arterioles (39±4 μm diameter, n=22 vessels) from EX hearts (n=14), ADO increased P^α-lact_s and P^PSA_s by 32 and 65% respectively, indicating that receptor-mediated changes in permeability were also sensitive to exercise training. These data demonstrate that, for coronary arterioles, permeability to macromolecules adapts to exercise training. The adaptive mechanisms may involve more than one structural component of the vessel wall as the changes in permeability were size-dependent.     

<Emphasis Type="Italic">V</Emphasis>O<Subscript>2</Subscript>max during successive maximal efforts

The concept of VO₂max has been a defining paradigm in exercise physiology for >75 years. Within the last decade, this concept has been both challenged and defended. The purpose of this study was to test the concept of VO₂max by comparing VO₂ during a second exercise bout following a preliminary maximal effort exercise bout. The study had two parts. In Study #1, physically active non-athletes performed incremental cycle exercise. After 1-min recovery, a second bout was performed at a higher power output. In Study #2, competitive runners performed incremental treadmill exercise and, after 3-min recovery, a second bout at a higher speed. In Study #1 the highest VO₂ (bout 1 vs. bout 2) was not significantly different (3.95 ± 0.75 vs. 4.06 ± 0.75 l min⁻¹). Maximal heart rate was not different (179 ± 14 vs. 180 ± 13 bpm) although maximal V _E was higher in the second bout (141 ± 36 vs. 151 ± 34 l min⁻¹). In Study #2 the highest VO₂ (bout 1 vs. bout 2) was not significantly different (4.09 ± 0.97 vs. 4.03 ± 1.16 l min⁻¹), nor was maximal heart rate (184 + 6 vs. 181 ± 10 bpm) or maximal V _E (126 ± 29 vs. 126 ± 34 l min⁻¹). The results support the concept that the highest VO₂ during a maximal incremental exercise bout is unlikely to change during a subsequent exercise bout, despite higher muscular power output. As such, the results support the “classical” view of VO₂max.     

Epidermal growth factor and insulin short‐term increase hPepT1‐mediated glycylsarcosine uptake in Caco‐2 cells

Aims: Little is known about the physiological regulation of the human intestinal di/tri‐peptide transporter, hPepT1. In the present study we evaluated the effects of epidermal growth factor (EGF) and insulin on hPepT1‐mediated dipeptide uptake in the intestinal cell line Caco‐2. Methods: Caco‐2 cells were grown on filters for 23–27 days. Apical dipeptide uptake was measured using [¹⁴C]glycylsarcosine([¹⁴C]Gly‐Sar). HPepT1 mRNA levels were investigated using RT‐PCR, cytosolic pH was determined using the pH‐sensitive fluorescent probe BCECF. Results: Basolateral application of EGF increased [¹⁴C]Gly‐Sar uptake with an ED₅₀ value of 0.77 ± 0.25 ng mL^?1 (n = 3?6) and a maximal stimulation of 33 ± 2% (n = 3?6). Insulin stimulated [¹⁴C]Gly‐Sar uptake with an ED₅₀ value of 3.5 ± 2.0 ng mL^?1 (n = 3?6) and a maximal stimulation of approximately 18% (n = 3?6). Gly‐Sar uptake followed simple Michaelis‐Menten kinetics. K_m in control cells was 0.98 ± 0.11 mM (n = 8) and V_max was 1.86 ± 0.07 nmol cm^?2 min^?1 (n = 8). In monolayers treated with 200 ng mL^?1 of EGF, K_m was 1.11 ± 0.05 mM (n = 5) and V_max was 2.79 ± 0.05 nmol cm^?2 min^?1 (n = 5). In monolayers treated with 50 ng mL^?1 insulin, K_m was 1.03 ± 0.08 mM and V_max was 2.19 ± 0.06 nmol cm^?2 min^?1 (n = 5). Kinetic data thus indicates an increase in the number of active transporters, following stimulation. The incrased Gly‐Sar uptake was not accompanied by changes in hPepT1 mRNA, nor by measurable changes in cytosolic pH. Conclusions: Short‐term stimulation with EGF and insulin caused an increase in hPepT1‐mediated uptake of Gly‐Sar in Caco‐2 cell monolayers, which could not be accounted for by changes in hPepT1 mRNA or proton‐motive driving force.     

Influence of upper body position on middle cerebral artery blood velocity during continuous positive airway pressure breathing

Continuous positive airway pressure (CPAP) is a treatment modality for pulmonary oxygenation difficulties. CPAP impairs venous return to the heart and, in turn, affects cerebral blood flow (CBF) and augments cerebral blood volume (CBV). We considered that during CPAP, elevation of the upper body would prevent a rise in CBV, while orthostasis would challenge CBF. To determine the body position least affecting indices of CBF and CBV, the middle cerebral artery mean blood velocity (MCA V _mean) and the near-infrared spectroscopy determined frontal cerebral hemoglobin content (cHbT) were evaluated in 11 healthy subjects during CPAP at different body positions (15° head-down tilt, supine, 15°, 30° and 45° upper body elevation). In the supine position, 10 cmH₂O of CPAP reduced MCA V _mean by 9 ± 3% and increased cHbT by 4 ± 2 μmol/L (mean ± SEM); (P < 0.05). In the head-down position, CPAP increased cHbT to 13 ± 2 μmol/L but left MCA V _mean unchanged. Upper body elevation by 15° attenuated the CPAP associated reduction in MCA V _mean (−7 ± 2%), while cHbT returned to baseline (1 ± 2 μmol/L). With larger elevation of the upper body MCA V _mean decreased progressively to −17 ± 3%, while cHbT remained unchanged from baseline. These results suggest that upper body elevation by ∼15° during 10 cmH₂O CPAP prevents an increase in cerebral blood volume with minimal effect on cerebral blood flow.     

Cardiac response to exercise in normal-weight and obese, Hispanic men and women: implications for exercise prescription

Aim: The effects of obesity on cardiac function during incremental exercise to peak oxygen consumption (VO_2peak) have not been previously described. The purpose of this study was to compare submaximal and maximal cardiac function during exercise in normal‐weight and obese adults. Methods: Normal‐weight (n = 20; means ± SE: age = 21.9 ± 0.5 years; BMI = 21.8 ± 0.4 kg m^?2) and obese (n = 15; means ± SE: age = 25.1 ± 5.2 years; BMI = 34.1 ± 01.0 kg m^?2) participants were assessed for body composition, VO_2peak and cardiac variables (thoracic bioimpedance analysis) at rest and at heart rates (HR) of 110, 130, 150 and 170 beats min^?1 and maximal HR during incremental cycling exercise to exhaustion. Differences between groups were assessed with mixed‐model ancova with repeated measures. Cardiac variables were statistically indexed for body surface area and resting HR. VO₂ and arteriovenous oxygen difference (a‐vO₂) were statistically indexed for fat‐free mass and resting HR. Results: Significant main effects for group indicated obese participants had higher cardiac output (Q) index and stroke volume (SV) index but lower ejection fraction (EF) and a‐vO₂ index during incremental exercise to exhaustion compared with their normal‐weight peers, despite similar submaximal and maximal VO₂ and absolute power outputs (P < 0.05). Conclusions: Our findings suggest that although Q index and SV index were higher in obese, young adults, EF and a‐vO₂ index were significantly lower when compared to matched, normal‐weight adults.     

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.     

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.     

Operating lung volumes are affected by exercise mode but not trunk and hip angle during maximal exercise

Introduction

Despite VO_2peak being, generally, greater while running compared to cycling, ventilation (V _E) during maximal exercise is less while running compared to cycling. Differences in operating lung volumes (OLV) between maximal running and cycling could be one explanation for previously observed differences in V _E and this could be due to differences in body position e.g., trunk/hip angle during exercise.

Purpose

We asked whether OLV differed between maximal running and cycling and if this difference was due to trunk/hip angle during exercise.

Methods

Eighteen men performed three graded maximal exercise tests; one while running, one while cycling in the drop position (i.e., extreme hip flexion), and one while cycling upright (i.e., seated with thorax upright). Resting flow-volume characteristics were measured in each body position to be used during exercise. Tidal flow-volume loops were measured throughout the exercise.

Results

V _E during maximal running (148.8 ± 18.9 L min^?1) tended to be lower than during cycling in the drop position (158.5 ± 24.7 L min^?1; p = 0.07) and in the upright position (158.5 ± 23.7 L min^?1; p = 0.06). End-inspiratory and end-expiratory lung volumes (EILV, EELV) were significantly larger during drop cycling compared to running (87.1 ± 4.1 and 35.8 ± 6.2 vs. 83.9 ± 6.0 and 33.0 ± 5.7 % FVC), but only EILV was larger during upright cycling compared to running (88.2 ± 3.5 % FVC). OLV and V _E did not differ between cycling positions.

Conclusion

Since OLV are altered by exercise mode, but cycling position did not have a significant impact on OLV, we conclude that trunk/hip angle is likely not the primary factor determining OLV during maximal exercise.