Sympathetic neural discharge and vascular resistance during exercise in humans

The purpose of this study was to determine the relationship between changes in efferent muscle sympathetic nerve activity (MSNA) to the lower leg and calf vascular resistance (CVR) during isometric exercise in humans. We made intraneural (microneurographic) determinations of MSNA in the right leg (peroneal nerve) while simultaneously measuring calf blood flow to the left leg, arterial pressure, and heart rate in 10 subjects before (control), during, and after (recovery) isometric handgrip exercise performed for 2.5 min at 15, 25, and 35% of maximal voluntary contraction (MVC). Heart rate and arterial pressure increased above control within the initial 30 s of handgrip at all levels, and the magnitudes of the increases at end contraction were proportional to the intensity of the exercise. In general, neither MSNA nor CVR increased significantly above control levels during handgrip at 15% MVC. Similarly, neither variable increased above control during the initial 30 s of handgrip at 25 and 35% MVC; however, during the remainder of the contraction period, progressive, parallel increases were observed in MSNA and CVR (P less than 0.05). The correlation coefficients relating changes in MSNA to changes in CVR for the individual subjects averaged 0.63 +/- 0.07 (SE) (range 0.30-0.91) and 0.94 +/- 0.06 (range 0.80-0.99) for the 25 and 35% MVC levels, respectively. During recovery, both MSNA and CVR returned rapidly toward control levels. These findings demonstrate that muscle sympathetic nerve discharge and vascular resistance in the lower leg are tightly coupled during and after isometric arm exercise in humans. Furthermore, the exercise-induced adjustments in the two variables are both contraction intensity and time dependent.     

Visual function after prolonged bed rest

The present study evaluated the claim of earlier reports, that of bed rest-induced alterations in visual function. Indices of visual function were studied in 10 healthy male subjects, during 35 days of horizontal bed rest. Before and after the 35 day bed rest, both eyes of all subjects were examined for visual acuity, intraocular pressure, contrast sensitivity, stereopsis and visual field. Pre- and post-bed rest values were compared with Student's T-test. There were no significant differences in any of the measured indices of visual function.     

Cardiac atrophy after bed rest and spaceflight.

Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity of cardiac muscle under different loading conditions.     

Sympathetic nervous activity decreases during head-down bed rest but not during microgravity.

We tested the hypothesis that sympathoadrenal activity in humans is low during spaceflight and that this effect can be simulated by head-down bed rest (HDBR). Platelet norepinephrine and epinephrine were measured as indexes of long-term changes in sympathoadrenal activity. Ten normal healthy subjects were studied before and during HDBR of 2-wk duration, as well as during an ambulatory study period of a similar length. Platelet norepinephrine concentrations (half-life = 2 days) were studied in five cosmonauts, 2 wk before launch, within 12 h after landing after 11-12 days of flight, and at least 2 wk after return to Earth. Because of the long half-life of platelet norepinephrine, data obtained early after landing would still reflect the microgravity state. Platelet norepinephrine decreased markedly during HDBR (P < 0.001), whereas there were no significant changes when subjects were ambulatory. Platelet epinephrine did not change during HDBR. During microgravity, platelet norepinephrine and epinephrine increased in four of the five cosmonauts. Platelet norepinephrine concentrations expressed in percentage of preflight and pre-HDBR values, respectively, were significantly different during microgravity compared with HDBR [153 +/- 28% (mean +/- SE) vs. 60 +/- 6%, P < 0.004]. Corresponding values for platelet epinephrine were also significant (293 +/- 85 vs. 90 +/- 12%, P < 0.01). The mechanism of the platelet norepinephrine and epinephrine response during spaceflight flight is most likely related to the concomitant decrease in plasma volume. HDBR cannot be applied to simulate changes in sympathoadrenal activity during microgravity.     

Alpha-adrenergic vascular responsiveness to sympathetic nerve activity is intact after head-down bed rest in humans

Space-flight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), cause cardiovascular deconditioning in humans. Because sympathetic vasoconstriction plays a very important role in circulation, we examined whether HDBR impairs alpha-adrenergic vascular responsiveness to sympathetic nerve activity. We subjected eight healthy volunteers to 14 days of HDBR and before and after HDBR measured calf muscle sympathetic nerve activity (MSNA; microneurography) and calf blood flow (venous occlusion plethysmography) during sympathoexcitatory stimulation (rhythmic handgrip exercise). HDBR did not change the increase in total MSNA (P = 0.97) or the decrease in calf vascular conductance (P = 0.32) during exercise, but it did augment the increase in calf vascular resistance (P = 0.0011). HDBR augmented the transduction gain from total MSNA into calf vascular resistance, assessed as the least squares linear regression slope of vascular resistance on total MSNA (0.05 +/- 0.02 before HDBR, 0.20 +/- 0.06 U.min-1.burst-1 after HDBR, P = 0.0075), but did not change the transduction gain into calf vascular conductance (P = 0.41). Our data indicate that alpha-adrenergic vascular responsiveness to sympathetic nerve activity is preserved in the supine position after HDBR in humans.     

Lung function during and after prolonged head-down bed rest.

We determined the effects of prolonged head-down tilt bed rest (HDT) on lung mechanics and gas exchange. Six subjects were studied in supine and upright postures before (control), during [day 113 (D113)], and after (R + number of days of recovery) 120 days of HDT. Peak expiratory flow (PF) never differed between positions at any time and never differed from controls. Maximal midexpiratory flow (FEF(25-75%)) was lower in the supine than in the upright posture before HDT and was reduced in the supine posture by about 20% between baseline and D113, R + 0, and R + 3. The diffusing capacity for carbon monoxide corrected to a standardized alveolar volume (volume-corrected DL(CO)) was lower in the upright than in the supine posture and decreased in both postures by 20% between baseline and R + 0 and by 15% between baseline and R + 15. Pulmonary blood flow (Q(C)) increased from R + 0 to R + 3 by 20 (supine) and 35% (upright). As PF is mostly effort dependent, our data speak against major respiratory muscle deconditioning after 120 days of HDT. The decrease in FEF(25-75%) suggests a reduction in elastic recoil. Time courses of volume-corrected DL(CO) and Q(C) could be explained by a decrease in central blood volume during and immediately after HDT.     

WISE 2005: vascular responses to 60-day bed rest in women

WISE-2005 studied 24 women during a 60-day head down bed rest (HDBR) who look part in an exercise countermeasure (LBNP-treadmill plus flywheel, EX) and no-exercise (No-EX). We conducted a series of experiments to explore changes in cardiovascular function and the ability of EX to prevent these changes. Resting arterial diameter in the arm was not affected but the leg arteries (femoral and popliteal) were significantly reduced in Np-EX, but was increased in EX. In this study we report on drug stimulated responses with sublingual nitroglycerin and infused isoproterenol. Heart rate increased in response to nitroglycerin with larger increases in No-EX after HDBR. Likewise during isoproterenol infusion the HR increase was greater after HDBR in the No-EX group. In all cases, the higher HR was associated with lower stroke volume in No-EX while stroke volume was protected in EX. These data do not support a change in sensitivity of beta-adrenergic receptors after HDBR. The leg vascular resistance decreased in response to isoproterenol and it decreased to a greater extent in No-EX than EX. These data were consistent with observations of lower leg vascular resistance during orthostatic challenge tests after HDBR. We conclude that consistent changes in cardiovascular function in the No-EX were detected by different methods that point to mechanisms contributing to orthostatic intolerance after HDBR.     

Attenuated sympathetic nerve responses after 24 hours of bed rest

Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.     

Gender differences in muscle strength after 20 days bed rest

In the previous studies, when Bed rest (BR) was prolonged over 2 weeks, muscle mass and strength began progressively to become reduced. There are many publications investigating the changes in skeletal muscles during inactivity. However it is still unclear whether the changing degrees of muscle mass and strength not only in antigravity muscles but also in non-antigravity muscles differ between males and females. So, the purpose of this study is to investigate gender difference in the effect of 20 days of BR (BR 20) on regional muscle mass and strength of the arm and leg.     

Regulation of muscle sympathetic nerve activity after bed rest deconditioning

Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.     

Pathophysiology of orthostatic hypotension after bed rest: paradoxical sympathetic withdrawal

Although orthostatic hypotension is a common clinical syndrome after spaceflight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), the pathophysiology remains unclear. The authors' hypothesis that a decrease in sympathetic nerve activity is the major pathophysiology underlying orthostatic hypotension after HDBR was tested in a study involving 14-day HDBR in 22 healthy subjects who showed no orthostatic hypotension during 15-min 60 degrees head-up tilt test (HUT) at baseline. After HDBR, 10 of 22 subjects demonstrated orthostatic hypotension during 60 degrees HUT. In subjects with orthostatic hypotension, total activity of muscle sympathetic nerve activity (MSNA) increased less during the first minute of 60 degrees HUT after HDBR (314% of resting supine activity) than before HDBR (523% of resting supine activity, P < 0.05) despite HDBR-induced reduction in plasma volume (13% of plasma volume before HDBR). The postural increase in total MSNA continued during several more minutes of 60 degrees HUT while arterial pressure was maintained. Thereafter, however, total MSNA was paradoxically suppressed by 104% of the resting supine level at the last minute of HUT (P < 0.05 vs. earlier 60 degrees HUT periods). The suppression of total MSNA was accompanied by a 22 +/- 4-mmHg decrease in mean blood pressure (systolic blood pressure <80 mmHg). In contrast, orthostatic activation of total MSNA was preserved throughout 60 degrees HUT in subjects who did not develop orthostatic hypotension. These data support the hypothesis that a decrease in sympathetic nerve activity is the major pathophysiological factor underlying orthostatic hypotension after HDBR. It appears that the diminished sympathetic activity, in combination with other factors associated with HDBR (e.g., hypovolemia), may predispose some individuals to postural hypotension.     

Lower limb skeletal muscle function after 6wk of bed rest

Berg, H. E., L. Larsson, and P. A. Tesch. Lower limbskeletal muscle function after 6 wk of bed rest. J. Appl. Physiol. 82(1): 182-188, 1997.Force,electromyographic (EMG) activity, muscle mass, and fibercharacteristics were studied in seven healthy men before and after 6 wkof bed rest. Maximum voluntary isometric and concentric knee extensortorque decreased (P < 0.05)uniformly across angular velocities by 25-30% after bed rest.Maximum quadricep rectified EMG decreased by 19 ± 23%, whereassubmaximum (100-Nm isometric action) EMG increased by 44 ± 28%.Knee extensor muscle cross-sectional area (CSA), assessed by usingmagnetic resonance imaging, decreased by 14 ± 4%. Maximum torqueper knee extensor CSA decreased by 13 ± 9%. Vastus lateralis fiberCSA decreased 18 ± 14%. Neither type I, IIA, and IIB fiberpercentages nor their relative proportions of myosin heavy chain (MHC)isoforms were altered after bed rest. Because the decline in strengthcould not be entirely accounted for by decreased muscle CSA, it issuggested that the strength loss is also due to factors resulting indecreased neural input to muscle and/or reduced specifictension of muscle, as evidenced by a decreased torque/EMG ratio.Additionally, it is concluded that muscle unloading in humans does notinduce important changes in fiber type or MHC composition or in vivomuscle contractile properties.

     

Maximal instantaneous muscular power after prolonged bed rest in humans.

A reduction in lower limb cross-sectional area (CSA) occurs after bed rest (BR). This should lead to an equivalent reduction in maximal instantaneous muscular power (W(p)) if the body segments' lengths remain unchanged. W(p) was determined during maximal jumps off both feet on a force platform before and on days 2, 6, 10, 32, and 48 after a 42-day duration BR. CSA of thigh muscles was measured by magnetic resonance imaging before and on day 5 after BR. Before BR, W(p) was 3.63 +/- 0.43 kW or 48.6 +/- 3.3 W/kg. On days 2 and 6 after BR, W(p) was reduced by 23.7 +/- 6.9 and 22.7 +/- 5.4% (P < 0.01), respectively. Thigh extensors CSA (CSAEXT) was 16.7 +/- 4.7% (P < 0.01) lower than before. When normalized per CSAEXT, W(p) was reduced by only 4.8 +/- 4.5% (P < 0.05). By day 48 of recovery, W(p) had returned to baseline values. Therefore, if W(p) is appropriately normalized for CSA of the extensor muscles, the reduction in CSAEXT explains most of the decrease in W(p) decrease after BR. Other factors such as a deficit in neural activation or a decrease in fiber-specific tension may account for only 5% of the W(p) loss after BR.     

Baroreflex during exercise in different postures before and after 20-days bed rest

Vagal-cardiac baroreflex functions in young healthy humans (n=6) were investigated in four different conditions; supine rest, seated rest, supine and seated exercise (50 watts) before and after 20-day horizontal bed rest. By selectively stimulating carotid baroreceptors using a neck pressure and suction technique, the primary finding was that the baroreflex sensitivity tuation at which we observed a tendency for an attenuation (0.05相似文献   

Fluid volume and osmoregulation in humans after a week of head-down bed rest

Body fluid homeostasis was investigated during chronic bed rest (BR) and compared with that of acute supine conditions. The hypothesis was tested that 6 degrees head-down BR leads to hypovolemia, which activates antinatriuretic mechanisms so that the renal responses to standardized saline loading are attenuated. Isotonic (20 ml/kg body wt) and hypertonic (2.5%, 7.2 ml/kg body wt) infusions were performed in eight subjects over 20 min following 7 and 10 days, respectively, of BR during constant sodium intake (200 meq/day). BR decreased body weight (83.0 +/- 4.8 to 81.8 +/- 4.4 kg) and increased plasma osmolality (285.9 +/- 0.6 to 288.5 +/- 0.9 mosmol/kgH(2)O, P < 0.05). Plasma ANG II doubled (4.2 +/- 1.2 to 8.8 +/- 1.8 pg/ml), whereas other endocrine variables decreased: plasma atrial natriuretic peptide (42 +/- 3 to 24 +/- 3 pg/ml), urinary urodilatin excretion rate (4.5 +/- 0.3 to 3.2 +/- 0.1 pg/min), and plasma vasopressin (1.7 +/- 0.3 to 0.8 +/- 0.2 pg/ml, P < 0.05). During BR, the natriuretic response to the isotonic saline infusion was augmented (39 +/- 8 vs. 18 +/- 6 meq sodium/350 min), whereas the response to hypertonic saline was unaltered (32 +/- 8 vs. 29 +/- 5 meq/350 min, P < 0.05). In conclusion, BR elicits antinatriuretic endocrine signals, but it does not attenuate the renal natriuretic response to saline stimuli in men; on the contrary, the response to isotonic saline is augmented.     

Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution

Bamman, Marcas M., Mark S. F. Clarke, Daniel L. Feeback,Robert J. Talmadge, Bruce R. Stevens, Steven A. Lieberman, and MichaelC. Greenisen. Impact of resistance exercise during bed rest onskeletal muscle sarcopenia and myosin isoform distribution. J. Appl. Physiol. 84(1): 157-163, 1998.Because resistance exercise (REx) and bed-rest unloading (BRU)are associated with opposing adaptations, our purpose was to test theefficacy of REx against the effects of 14 days of BRU on theknee-extensor muscle group. Sixteen healthy men were randomly assignedto no exercise (NoEx; n = 8) or REx(n = 8). REx performed five sets ofleg press exercise with 80-85% of one repetition maximum (1 RM)every other day during BRU. Muscle samples were removed from the vastuslateralis muscle by percutaneous needle biopsy. Myofiber distributionwas determined immunohistochemically with three monoclonal antibodiesagainst myosin heavy chain (MHC) isoforms (I, IIa, IIx). MHCdistribution was further assessed by quantitative gel electrophoresis.Dynamic 1-RM leg press and unilateral maximum voluntary isometriccontraction (MVC) were determined. Maximal neural activation (root meansquared electromyogram) and rate of torque development (RTD) weremeasured during MVC. Reductions(P < 0.05) in type I (15%) and typeII (17%) myofiber cross-sectional areas were found in NoEx but not inREx. Electrophoresis revealed no changes in MHC isoform distribution. The percentage of type IIx myofibers decreased(P < 0.05) in REx from 9 to 2% anddid not change in NoEx. 1 RM was reduced(P < 0.05) by 9% in NoEx but wasunchanged in REx. MVC fell by 15 and 13% in NoEx and REx,respectively. The agonist-to-antagonist root mean squaredelectromyogram ratio decreased (P < 0.05) 19% in REx. RTD slowed (P < 0.05) by 54% in NoEx only. Results indicate that REx preventedBRU-induced myofiber atrophy and also maintained training-specificstrength. Unlike spaceflight, BRU did not induce shifts in myosinphenotype. The reported benefits of REx may prove useful in prescribingexercise for astronauts in microgravity.

     

WISE 2005: altered cerebrovascular autoregulation after 60 day head-down bed rest

We tested the hypothesis that 60 days of head-down bed rest (HDBR) would affect cerebrovascular autoregulation and that this change would be correlated with changes in tolerance to the upright posture. Twenty-four healthy women (32 +/- 4 yrs) participated in a 60-d bed rest study at the MEDES Clinic in Toulouse, France. End tidal CO2 (ETCO2), continuous blood pressure (BP), middle cerebral artery (MCA) velocity and time to presyncope (endpoint) were measured during an orthostatic tolerance test conducted before/after bed rest. Given the large range of change in tolerance even within assigned countermeasure groups, we separated subjects for this analysis on the basis of the change in endpoint (Delta endpoint) pre- to post-bed rest. Autoregulation and CO2 responsiveness were evaluated on a different day from a two-breath test with intermittent hypercapnic exposure. Autoregressive moving average (ARMA) modeled the two confounding inputs, BP and CO2, on cerebrovascular blood flow. The cerebrovascular resistance index (CVRi) was expected to decrease following a decrease in BP at the MCA to assist in maintenance of cerebral blood flow. Subjects with the smallest Delta endpoint after bed rest had a 78% increase in the gain of the BP --> CVRi response. Meanwhile, the groups with greater decline in orthostatic tolerance post-HDBR had no change in the gain of this response. ETCO2 was lower overall following HDBR, decreasing from 41.8 +/- 3.4 to 40.2 +/- 3.0 in supine rest, 37.9 +/- 3.4 to 33.3 +/- 4.0 in early tilt, and 29.5 +/- 4.4 to 27.1 +/- 5.1 at pre-syncope. There was however, higher MCA velocity at any ETCO2 for post- compared to pre-HDBR. In summary, changes in autoregulation were found only in those subjects who had the smallest change from pre- to post-HDBR orthostatic tolerance. The changes may assist in buffering changes in cerebral blood flow during orthostatic hypotension post-HDBR. The reduction in ETCO2 after bed rest might be due to a change in chemoreceptor response to blood CO2, but the cerebrovascular system seems to have completely compensated.