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.     

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.     

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.     

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.     

Coupling between cerebral blood flow and cerebral blood volume: Contributions of different vascular compartments

A better understanding of the coupling between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is vital for furthering our understanding of the BOLD response. The aim of this study was to measure CBF‐CBV coupling in different vascular compartments during neural activation. Three haemodynamic parameters were measured during a visual stimulus. Look‐Locker flow‐sensitive alternating inversion recovery was used to measure changes in CBF and arterial CBV (CBV_a) using sequence parameters optimized for each contrast. Changes in total CBV (CBV_tot) were measured using a gadolinium‐based contrast agent technique. Haemodynamic changes were extracted from a region of interest based on voxels that were activated in the CBF experiments. The CBF‐CBV_tot coupling constant α_tot was measured as 0.16 ± 0.14 and the CBF‐CBV_a coupling constant α_a was measured as 0.65 ± 0.24. Using a two‐compartment model of the vasculature (arterial and venous), the change in venous CBV (CBV_v) was predicted for an assumed value of baseline arterial and venous blood volume. These results will enhance the accuracy and reliability of applications that rely on models of the BOLD response, such as calibrated BOLD.     

Near-infrared spectrophotometry determined brain oxygenation during fainting

During orthostatic hypotension we evaluated whether presyncopal symptoms relate to a reduced brain oxygenation. Nine subjects performed 50° head-up tilt for 1 h and eight subjects were followed during 2 h of supine rest and during 1 h of 10° head-down tilt. Cerebral perfusion was assessed by transcranial Doppler determined middle cerebral artery blood velocity (MCA v_mean), while brain blood oxygenation was assessed by near-infrared spectrophotometry determined concentration changes for oxygenated (ΔHbO₂) and deoxygenated haemoglobin and brain cell oxygenation by the oxidized cytochrome c concentration (ΔCytO₂). During head-up tilt, six volunteers developed presyncopal symptoms and mean arterial pressure (88 (78–103) to 68 (57–79) mmHg; median and range), heart rate (96 (72–111) to 65 (50–107) beats min^?1), MCA v_mean (59 (51–82) to 41 (29–56) cm s^?1), ΔHbO₂ (by ?5.3 (?3.0 to ?14.8) μmol l^?1) and ΔCytO₂ were reduced (by ?0.2 (?0.1 to ?0.4) μmol l^?1; P < 0.05). During tilt down the cardiovascular variables recovered immediately and ΔHbO₂ increased to 2.2 (?0.9–12.0) mmol L^?1 above the resting value and also ΔCytO₂ recovered. In the nonsyncopal head-up tilted subjects as in the controls, blood pressure, heart rate, MCA v_mean and brain oxygenation indices remained stable. The results suggest that during orthostasis, presyncopal symptoms relate not only to cerebral hypoperfusion but also to reduced brain oxygenation.     

Cerebral oxygenation is reduced during hyperthermic exercise in humans

Aim: Cerebral mitochondrial oxygen tension (P_mitoO₂) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO₂) combined with hyperventilation-induced attenuation of cerebral blood flow (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods: This study evaluated the effect of heat stress during exercise on P_mitoO₂ calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences in eight males [27 ± 6 years (mean ± SD) and maximal oxygen uptake (VO_2max) 63 ± 6 mL kg⁻¹ min⁻¹]. Results: The CBF, CMRO₂ and P_mitoO₂ remained stable during 1 h of moderate cycling (170 ± 11 W, ∼50% of VO_2max, RPE 9–12) in normothermia (core temperature of 37.8 ± 0.4 °C). In contrast, when hyperthermia was provoked by dressing the subjects in watertight clothing during exercise (core temperature 39.5 ± 0.2 °C), P_mitoO₂ declined by 4.8 ± 3.8 mmHg (P < 0.05 compared to normothermia) because CMRO₂ increased by 8 ± 7% at the same time as CBF was reduced by 15 ± 13% (P < 0.05). During exercise with heat stress, RPE increased to 19 (19–20; P < 0.05); the RPE correlated inversely with P_mitoO₂ (r² = 0.42, P < 0.05). Conclusion: These data indicate that strenuous exercise in the heat lowers cerebral P_mitoO₂, and that exercise capacity in this condition may be dependent on maintained cerebral oxygenation.     

Effects of intermittent hypoxia on the cerebrovascular responses to submaximal exercise in humans

Intermittent hypoxia (IH) has been shown to alter the ventilatory and cardiovascular responses to submaximal exercise; however, the effect of IH on the cerebral blood flow (CBF) response to submaximal exercise has not been determined. This study tested the hypothesis that IH would blunt the CBF response during eucapnic and hypercapnic exercise. Nine healthy males underwent 10 consecutive days of isocapnic IH (oxyhaemoglobin saturation = 80%, 1 h day⁻¹). Ventilatory, cardiovascular, and cerebrovascular responses to cycle exercise (50, 100, and 150 W) were measured before and after IH. Carbon dioxide (5% CO₂), a mediator of CBF during exercise, was administered for 2 min of each exercise stage. Over the 10 days of IH, there was an increase in minute ventilation during the IH exposures (P < 0.05). Although exercise produced increases in middle cerebral artery mean velocity (MCA V _mean), and mean arterial pressure (P < 0.05), there was no effect of IH. Similarly, hypercapnic exercise increased and MCA V _mean (P < 0.05); however, the magnitude of the response was unchanged following IH. Our findings indicate that ten daily hypoxia exposures does not alter the CBF response to submaximal exercise.     

Cerebral Blood Flow Velocity,Erythrocyte Deformability and Alcohol Intake

The aim of the study was to determine if there is a relationship between low blood flow velocity in the cerebral arteries and erythrocyte deformability in heavy alcohol drinkers. The study comprised 47 heavy alcohol drinkers (mean age 47 years). All of them drank daily more than 84 g of alcohol (84–400 g). Blood flow velocity (V _mean) in intracranial arteries was determined by transcranial Doppler. Erythrocyte membrane biophysical properties were estimated using the method of cation-osmotic haemolysis (COH). The present study revealed a significant decrease in V _mean in all examined arteries, with p= <0.01 in the middle (MCA) and posterior (PCA) cerebral arteries and p= <0.05 in the anterior cerebral artery (ACA) when compared with age-matched controls. Cation-osmotic haemolysis in the low ionic strength of the incubating medium (15.4 mmol/l NaCl) as well as in the high ionic strength (123.2–154.0 mmol/l NaCl) was significantly decreased (p<0.001–0.01). This means that changes in both parts of the erythrocyte membrane (actin–spectrin complex and membrane lipid bilayer) are the cause of decreased erythrocyte deformability. We conclude that one of the factors which can cause low blood flow velocity (a possible risk factor for stroke) is decreased cation-osmotic haemolysis of erythrocytes.     

Effects of aging on the cerebrovascular orthostatic response

When healthy subjects stand up, it is associated with a reduction in cerebral blood velocity and oxygenation although cerebral autoregulation would be considered to prevent a decrease in cerebral perfusion. Aging is associated with a higher incidence of falls, and in the elderly falls may occur particularly during the adaptation to postural change. This study evaluated the cerebrovascular adaptation to postural change in 15 healthy younger (YNG) vs. 15 older (OLD) subjects by recordings of the near-infrared spectroscopy-determined cerebral oxygenation (cO₂Hb) and the transcranial Doppler-determined mean middle cerebral artery blood velocity (MCA V_mean). In OLD (59 (52-65) years) vs. YNG (29 (27-33) years), the initial postural decline in mean arterial pressure (−52 ± 3% vs. −67 ± 3%), cO₂Hb (−3.4 ± 2.5 μmol l⁻¹ vs. −5.3 ± 1.7 μmol l⁻¹) and MCA V_mean (−16 ± 4% vs. −29 ± 3%) was smaller. The decline in MCA V_mean was related to the reduction in MAP. During prolonged orthostatic stress, the decline in MCA V_meanand cO₂Hb in OLD remained smaller. We conclude that with healthy aging the postural reduction in cerebral perfusion becomes less prominent.     

Ketamine blocks voltage-gated K+ channels and causes membrane depolarization in rat mesenteric artery myocytes

Clinical doses of ketamine typically increase blood pressure, heart rate, and cardiac output. However, the precise mechanism by which ketamine produces these cardiovascular effects remains unclear. The voltage-gated K⁺ (K_V) channel is the major regulator of resting membrane potential (E _m) and vascular tone in many arteries. Therefore, we sought to evaluate the effects of ketamine on K_V currents using the standard whole-cell patch clamp recordings in single myocytes, enzymatically dispersed from rat mesenteric arteries. Ketamine [(±)-racemic mixture] inhibited K_V currents reversibly and concentration dependently with a K _d of 566.7 ± 32.3 μM and Hill coefficient of 0.75 ± 0.03. The inhibition of K_V currents by ketamine was voltage independent, and the time courses of channel activation and inactivation were little affected. The effects of ketamine on steady-state activation and inactivation curves were also minimal. Use-dependent inhibition was not observed either. S(+)-ketamine inhibited K_V currents with similar potency and efficacy as the racemic mixture. The average resting E _m in rat mesenteric artery myocytes was −44.1 ± 4.2 mV, and both racemic and S(+)-ketamine induced depolarization of E _m (15.8 ± 3.6 and 24.3 ± 5.0 mV at 100 μM, respectively). We conclude that ketamine induces E _m depolarization in vascular myocytes by blocking K_V channels in a state-independent manner, which may contribute to the increased vascular tone and blood pressure produced by this drug under a clinical setting.     

Skin blood flow influences cerebral oxygenation measured by near-infrared spectroscopy during dynamic exercise

Purpose

Near-infrared spectroscopy (NIRS) is widely used to investigate cerebral oxygenation and/or neural activation during physiological conditions such as exercise. However, NIRS-determined cerebral oxygenated hemoglobin (O₂Hb) may not necessarily correspond to intracranial blood flow during dynamic exercise. To determine the selectivity of NIRS to assess cerebral oxygenation and neural activation during exercise, we examined the influence of changes in forehead skin blood flow (SkBF_head) on NIRS signals during dynamic exercise.

Methods

In ten healthy men (age: 20 ± 1 years), middle cerebral artery blood flow velocity (MCA V _mean, via transcranial Doppler ultrasonography), SkBF_head (via laser Doppler flowmetry), and cerebral O₂Hb (via NIRS) were continuously measured. Each subject performed 60 % maximum heart rate moderate-intensity steady-state cycling exercise. To manipulate SkBF_head, facial cooling using a mist of cold water (~4 °C) was applied for 3 min during steady-state cycling.

Results

MCA V _mean significantly increased during exercise and remained unchanged with facial cooling. O₂Hb and SkBF_head were also significantly increased during exercise; however, both of these signals were lowered with facial cooling and returned to pre-cooling values with the removal of facial cooling. The changes in O₂Hb correlated significantly with the relative percent changes in SkBF_head in each individual (r = 0.71–0.99).

Conclusions

These findings suggest that during dynamic exercise NIRS-derived O₂Hb signal can be influenced by thermoregulatory changes in SkBF_head and therefore, may not be completely reflective of cerebral oxygenation or neural activation.     

Influence of training status and exercise modality on pulmonary O<Subscript>2</Subscript> uptake kinetics in pubertal girls

The influence of training status on the oxygen uptake ( [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} ) response to heavy intensity exercise in pubertal girls has not previously been investigated. We hypothesised that whilst training status-related adaptations would be evident in the [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} , heart rate (HR) and deoxyhaemoglobin ([HHb]) kinetics of pubertal swimmers during both lower and upper body exercise, they would be more pronounced during upper body exercise. Eight swim-trained (T; 14.2 ± 0.7 years) and eight untrained (UT; 14.5 ± 1.3 years) girls completed a number of constant-work-rate transitions on cycle and upper body ergometers at 40% of the difference between the gas exchange threshold and peak [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} . The phase II [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} time constant (τ) was significantly shorter in the trained girls during both cycle (T: 21 ± 6 vs. UT: 35 ± 11 s; P < 0.01) and upper body exercise (T: 29 ± 8 vs. UT: 44 ± 8 s; P < 0.01). The [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} slow component was not influenced by training status. The [HHb] τ was significantly shorter in the trained girls during both cycle (T: 12 ± 2 vs. UT: 20 ± 6 s; P < 0.01) and upper body exercise (T: 13 ± 3 vs. UT: 21 ± 7 s; P < 0.01), as was the HR τ (cycle, T: 36 ± 5 vs. UT: 53 ± 9 s; upper body, T: 32 ± 3 vs. UT: 43 ± 2; P < 0.01). This study suggests that both central and peripheral factors contribute to the faster [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} kinetics in the trained girls and that differences are evident in both lower and upper body exercise.     

BOLD‐specific cerebral blood volume and blood flow changes during neuronal activation in humans

To understand and predict the blood‐oxygenation level‐dependent (BOLD) fMRI signal, an accurate knowledge of the relationship between cerebral blood flow (ΔCBF) and volume (ΔCBV) changes is critical. Currently, this relationship is widely assumed to be characterized by Grubb's power‐law, derived from primate data, where the power coefficient (α) was found to be 0.38. The validity of this general formulation has been examined previously, and an α of 0.38 has been frequently cited when calculating the cerebral oxygen metabolism change (ΔCMRo₂) using calibrated BOLD. However, the direct use of this relationship has been the subject of some debate, since it is well established that the BOLD signal is primarily modulated by changes in ‘venous’ CBV (ΔCBV_v, comprising deoxygenated blood in the capillary, venular, and to a lesser extent, in the arteriolar compartments) instead of total CBV, and yet ΔCBV_v measurements in humans have been extremely scarce. In this work, we demonstrate reproducible ΔCBV_v measurements at 3 T using venous refocusing for the volume estimation (VERVE) technique, and report on steady‐state ΔCBV_v and ΔCBF measurements in human subjects undergoing graded visual and sensorimotor stimulation. We found that: (1) a BOLD‐specific flow‐volume power‐law relationship is described by α = 0.23 ± 0.05, significantly lower than Grubb's constant of 0.38 for total CBV; (2) this power‐law constant was not found to vary significantly between the visual and sensorimotor areas; and (3) the use of Grubb's value of 0.38 in gradient‐echo BOLD modeling results in an underestimation of ΔCMRo₂. Copyright © 2009 John Wiley & Sons, Ltd.     

Cerebral cortical blood flow in rabbits during parabolic flights (hypergravity and microgravity)

We studied the effect of gravity on cerebral cortical blood flow (CBF), mean arterial blood pressure () and heart rate in six rabbits exposed to parabolic flights. The CBF was obtained using a laser-Doppler probe fixed on to a cranial window. Before weightlessness, the animals were exposed to chest-to-back directed acceleration (1.8–2.0 g). The CBF values were expressed as a percentage of CBF_o (mean CBF during 60 s before the 1st parabola). Propranolol (1 mg · kg⁻¹ IV) was given after the 11th parabola and pentobarbital (12–15 mg · kg⁻¹ IV) after the 16th parabola. Before the administration of the drugs, CBF increased (P < 0.01) during hypergravity [i.e. maximal CBF 151 (SD 64)% CBF_o. Simultaneously increased [maximal , 119 (SD 11) mmHg (P < 0.01)]. At the onset of weightlessness, CBF and reached maximal values [194 (SD 96)% CBF_o (P < 0.01) and 127 (SD 19) mmHg, (P < 0.01) respectively]. The microgravity-induced increase in CBF was transient since CBF returned to its baseline value after 8 (SD 2) s of microgravity. After propranolol administration, CBF was not statistically different during hypergravity but an elevation of CBF was still observed in weightlessness. The increases in CBF and also persisted during weightlessness after pentobarbital administration. These data would indicate that CBF of nonanesthetized rabbits increases during the first seconds of weightlessness and demonstrate the involvement of rapid active regulatory mechanisms since CBF returned to control values within 8 (SD 2) s. We concluded that this elevation in blood flow was not related to stress because it persisted after the administration of propranolol and pentobarbital. Accepted: 6 November 1997     

The exercise dose affects oxidative stress and brachial artery flow-mediated dilation in trained men

The aim of this investigation was to establish whether changes in oxidative stress and endothelial function following acute aerobic exercise are dose-dependent. Ten healthy trained men completed four exercise sessions: 50% VO_2peak for 30 min (moderate intensity moderate duration, MIMD), 50% VO_2peak for 60 min (moderate intensity long duration, MILD), 80% VO_2peak for 30 min (high intensity moderate duration, HIMD), and 80% VO_2peak for the time to reach the caloric equivalent of MIMD (high intensity short duration, HISD). Thiobarbituric acid reactive substances (TBARS) were measured as an index of oxidative stress and brachial artery flow-mediated dilation (FMD) was assessed as an index of endothelial function. Variables were measured at baseline, immediately post-exercise, 1 and 2 h post-exercise. Both HIMD (14.2 ± 2.5 μmol/L) and HISD (14.7 ± 1.9 μmol/L) TBARS differed from MIMD (11.8 ± 1.5 μmol/L) immediately post-exercise. TBARS increased from pre to immediately post-exercise for HIMD (12.6 ± 2.1 vs.14.2 ± 2.5 μmol/L) and HISD (12.3 ± 2.8 vs. 14.7 ± 1.9 μmol/L). Both MIMD (7.2 ± 2.2%) and HISD (7.6 ± 2.7%) FMD immediately post-exercise were greater than HIMD (4.7 ± 2.2%). An increase of FMD from pre to immediately post-exercise was found for MIMD (5.0 ± 2.5 vs. 7.2 ± 2.2%) and HISD (5.9 ± 2.4 vs. 7.6 ± 2.7%). These data suggest that acute exercise-induced TBARS are exercise intensity-dependent whereas FMD appears to improve following energy expenditure equivalent to 30 min 50% VO_2peak, regardless of intensity or duration.     

Acute and adaptive responses in humans to exercise in a warm, humid environment

 Acute and repeated exposure for 8–13 consecutive days to exercise in humid heat was studied. Twelve fit subjects exercised at 150 W [45% of maximum O₂ uptake (V.O₂,_max)] in ambient conditions of 35°C and 87% relative humidity which resulted in exhaustion after 45 min. Average core temperature reached 39.9 ± 0.1°C, mean skin temperature (T– _sk) was 37.9 ± 0.1°C and heart rate (HR) 152 ± 6 beats min^–1 at this stage. No effect of the increasing core temperature was seen on cardiac output and leg blood flow (LBF) during acute heat stress. LBF was 5.2 ± 0.3 l min^–1 at 10 min and 5.3 ± 0.4 l min^–1 at exhaustion (n = 6). After acclimation the subjects reached exhaustion after 52 min with a core temperature of 39.9 ± 0.1°C, T– _sk 37.7 ± 0.2°C, HR 146 ± 4 beats min^–1. Acclimation induced physiological adaptations, as shown by an increased resting plasma volume (3918 ± 168 to 4256 ± 270 ml), the lower exercise heart rate at exhaustion, a 26% increase in sweating rate, lower sweat sodium concentration and a 6% reduction in exercise V.O₂. Neither in acute exposure nor after acclimation did the rise of core temperature to near 40°C affect metabolism and substrate utilization. The physiological adaptations were similar to those induced by dry heat acclimation. However, in humid heat the effect of acclimation on performance was small due to physical limitations for evaporative heat loss. Received: 3 July 1996 / Received after revision: 26 September 1996 / Accepted: 7 January 1997     

Chronic intracerebroventricular delivery of the secretory phospholipase A2 inhibitor, 12-epi-scalaradial, does not improve outcome after focal cerebral ischemia–reperfusion in rats

Phospholipase A₂s (PLA₂s) seem to be involved in the pathophysiology of ischemic brain injury, but their specific role is far from being completely understood. The present study was carried out to ascertain how and to what extent secretory PLA₂s (sPLA₂s) activity influences outcome after cerebral ischemia–reperfusion, and to correlate this with the inflammatory response. To do this we used the potent and selective sPLA₂ inhibitor, 12-epi-scalaradial. Male Wistar rats were separated into three groups: a control group receiving intracerebroventricular vehicle, and two groups receiving intracerebroventricular 0.005 or 0.5 μg/h 12-epi-scalaradial. Every animal was subjected to middle cerebral artery (MCA) occlusion (90 min, intraluminal thread technique) under continuous monitorization of cerebrocortical perfusion (CP, laser-Doppler flowmetry), followed by reperfusion (3 days). Neurological status, infarct volume, and myeloperoxidase (MPO) activity were the main end points. Three days after the 90-min ischemia period, neurological examination did not reveal significant differences between the three groups of rats. Control rats showed a mean infarct volume of 145.9 ± 24.7 mm³ (21 ± 4.1% of the ipsilateral hemisphere volume), while mean infarct volume in rats treated with 0.005 or 0.5 μg/h 12-epi-scalaradial increased to 164.8 ± 86.8 mm³ (22.0 ± 10.9%) and 211.5 ± 12.2 mm³ (28 ± 3%, P < 0.05), respectively. Treatment with the highest dose of 12-epi-scalaradial (0.5 μg/h) increased MPO activity in the ipsilateral hemisphere by about 140% (from 0.59 ± 0.59 to 1.42 ± 1.03 units of activity/g of tissue in comparison with the control ischemic hemisphere, P < 0.05). Overall, our results point to a positive rather than a negative influence of sPLA₂ activity during ischemia. This, along with its inability to decrease the inflammatory response, does not allow to propose the use of 12-epi-scalardial as a potential drug for stroke therapy.     

Effects of different after-loads and knee angles on maximal explosive power of the lower limbs in humans

Maximal explosive power during two-leg jumps was measured on four sedentary subjects [mean age 43.0 (SD 10.3) years, mean height 1.74 (SD 0.04) m, mean body mass 73.5 (SD 1.3) kg] using a sledge apparatus with which both force and speed could be directly measured. Different after-loads were obtained by positioning the sledge at five different angles (SA, α) in respect to the horizontal so that m · g · sin α (where m is the sum of body mass and the mass of the sledge seat, g the acceleration due to gravity) decreased (on average) from 78% body mass at 30° to 27% body mass at 10°, thus simulating conditions of low gravity. The subjects were asked to jump maximally, without counter movement, starting from 70°, 90°, 110°, and 140° of knee angle (KA); the protocol being repeated at 10°, 15°, 20°, 25° and 30° SA. The average (W˙ _mean ⁺) power output during concentric exercise (CE) was found to decrease when the starting KA was increased, but to be unaffected by SA (i.e. by the after-load, the simulated low g). The higher values of W˙ _mean ⁺ were recorded at 90° KA [15.01 (SD 1.46) W · kg⁻¹, average for all subjects at all SA]. The subjects were also asked to perform counter movement (CMJ) and rebound jumps (RE) at the same SA as for CE. In CMJ and RE maximal power outputs were also found to be unaffected by the SA; W˙ _mean ⁺ amounted to 16.03 (SD 0.28) W · kg⁻¹ in CMJ and 16.88 (SD 0.36) W · kg⁻¹ in RE (average for all subjects at all SA). In CE, CMJ and RE, the instantaneous force at the onset of the positive speed phase (F _i) was found to increase linearly with SA (i.e. with increasing m · g · sin α), and the difference between F _i in CMJ or RE and F _i in CE (F _i in CMJ minus F _i in CE and F _i in RE minus F _i in CE) was unaffected by SA. This indicated that both maximal power and the elastic recoil were unaffected by simulated low g ranging from 1.71 m · s⁻² (at 10° SA) to 4.91 m · s⁻² (at 30° SA). Accepted: 9 March 2000