Repeated increases in blood flow, independent of exercise, enhance conduit artery vasodilator function in humans

This study aimed to determine the importance of repeated increases in blood flow to conduit artery adaptation, using an exercise-independent repeated episodic stimulus. Recent studies suggest that exercise training improves vasodilator function of conduit arteries via shear stress-mediated mechanisms. However, exercise is a complex stimulus that may induce shear-independent adaptations. Nine healthy men immersed their forearms in water at 42°C for three 30-min sessions/wk across 8 wk. During each session, a pneumatic pressure cuff was inflated around one forearm to unilaterally modulate heating-induced increases in shear. Forearm heating was associated with an increase in brachial artery blood flow (P<0.001) and shear rate (P<0.001) in the uncuffed forearm; this response was attenuated in the cuffed limb (P<0.005). Repeated episodic exposure to bilateral heating induced an increase in endothelium-dependent vasodilation in response to 5-min ischemic (P<0.05) and ischemic handgrip exercise (P<0.005) stimuli in the uncuffed forearm, whereas the 8-wk heating intervention did not influence dilation to either stimulus in the cuffed limb. Endothelium-independent glyceryl trinitrate responses were not altered in either limb. Repeated heating increases blood flow to levels that enhance endothelium-mediated vasodilator function in humans. These findings reinforce the importance of the direct impacts of shear stress on the vascular endothelium in humans.     

Heterogeneity in conduit artery function in humans: impact of arterial size

To determine whether conduit artery size affects functional responses, we compared the magnitude, time course, and eliciting shear rate stimulus for flow-mediated dilation (FMD) in healthy men (n = 20; 31 +/- 7 yr). Upper limb (brachial and radial) and lower limb (common and superficial femoral) FMD responses were simultaneously assessed, whereas popliteal responses were measured in the same subjects during a separate visit. Glyceryl trinitrate (GTN)-mediated responses were similarly examined. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter, blood flow, and shear rate continuously across the cardiac cycle. Baseline artery size correlated inversely with the FMD response (r = -0.57, P < 0.001). Within-artery comparisons revealed a significant inverse correlation between artery size and FMD% for the radial (r = -0.66, P = 0.001), brachial (r = -0.55, P = 0.01), and popliteal artery (r = -0.48, P = 0.03), but not for the superficial and common femoral artery. Normalization of FMD responses for differences in eliciting shear rate did not abolish the between-artery relationship for artery function and size (r = -0.48, P < 0.001), suggesting that differences between artery function responses were not entirely due to size-related differences in shear rate. This was reinforced by a significant between-artery correlation for GTN responses and baseline artery size (r = -0.74, P < 0.001). In summary, systematic differences exist in vascular function responses of conduit arteries that differ in size. This raises the possibility that differences in artery size within or between individuals may influence functional responses.     

Relationship between the modifications of bilateral deficit in upper and lower limbs by resistance training in humans

Maximal voluntary strength of simultaneous bilateral exertion is known to be small compared to the sum of the unilateral exertions. This phenomenon is called bilateral deficit and the purpose of this study was to investigate whether it operates in both upper and lower limbs. A group of 7 female and 32 male students were divided into 4 training groups and a control group. The unilateral arm or leg training group performed maximal isokinetic arm or leg extensions using each arm or leg unilaterally. The bilateral arm or leg training group trained using bilateral extensions of both arms or legs. The groups in training continued these two types of resistance exercise 3 days a week, for 6 weeks. The control subjects did not train. The improvement in power brought about by training was compared from the viewpoint of whether the limbs (arms or legs) were trained or not and whether the mode of test power exertion (bilateral or unilateral) was the same as performed during training or not. The power in the trained limbs using the same regime as that during training (3.0% after 3 weeks, 7.7% after 6 weeks) showed the largest improvement ratio. This agrees with the specificity theory in resistance training. The increase in power in untrained limbs using the same regime as during training (2.1% after 3 weeks, 3.5% after 6 weeks; P < 0.01) and the increase in power in the untrained limbs after the opposing mode of training (1.2% after 3 weeks, 2.2% after 6 weeks; P < 0.05) were larger than that of the controls (−2.5% after 3 weeks, −1.1% after 6 weeks). This suggests that the effect of resistance training was transferred to the untrained limbs (i.e. to the legs in the arm training group and to the arms in the leg training group). The degree of bilateral deficit (bilateral index, BI) in the trained limbs of the bilateral training group was shifted in a positive direction (4.2% after 3 weeks, 3.7% after 6 weeks) and that in the trained limbs of unilateral training group was shifted in a negative direction (−3.0% after 3 weeks, −5.4% after 6 weeks) by 6 weeks of training. The BI in the untrained limbs of the unilateral training group was shifted in a negative direction (−1.9% after 3 weeks, −4.5% after 6 weeks) by 6 weeks of training, whereas that in the untrained limbs of the bilateral training group was not shifted in a positive direction (−0.1% after 3 weeks, −2.4% after 6 weeks). These results would suggest that bilateral deficits in the upper and lower limbs are at least partially affected by some common mechanism at a supraspinal level. Accepted: 3 March 1998     

Effects of lower limb unloading on skeletal muscle mass and function in humans

A model to simulate effects of microgravity on skeletal muscle mass and function in humans has been developed. Unilateral lower limb unloading that allowed ankle, knee, and hip joint mobility was conducted in six healthy men by suspending one lower limb and having the subjects walk on crutches. They performed maximal unilateral concentric or eccentric quadriceps actions at different angular velocities before and after 4 wk of suspension and after 4 days and after 7 wk of uncontrolled recovery. Peak torque (PT) and angle-specific torque (AST) were measured. Muscle cross-sectional area (CSA) and radiological density (RD) of the thigh were assessed by means of computerized tomography. Concentric and eccentric PT and AST across speeds decreased (P less than 0.05) by 22 and 16%, respectively, in response to unloading. At 4 days of recovery PT (-11%) and AST (-7%) were still lower (P less than 0.05) than before. Muscle CSA and RD decreased (P less than 0.05) by 7 and 6%, respectively. After 7 wk of recovery PT, AST, CSA, and RD had returned to normal. The control limb showed no changes over the experimental period except for a 6% decrease (P less than 0.05) in RD. It is suggested that this human model of unloading could serve to simulate effects of microgravity on skeletal muscle mass and function because reductions in muscle mass and strength were of similar magnitude to those produced by bed rest.     

Directional sensitivity along the upper limb in humans

The capacity of four neurologically healthy young adults to distinguish opposing directions of cutaneous motion was determined at five different sites along the proximal-distal axis of the upper limb. Constant-velocity brushing stimuli (ranging from 0.5 to 32.0 cm/sec) were delivered through an aperture in a Teflon plate that was securely positioned in light contact with the skin. In one series of experiments, directional sensitivity in d' units was assessed at each site, using an aperture length of 0.75 cm. In a second series of experiments, the aperture length required to obtain the same criterion level of directional sensitivity at each site was determined. To attain the sensitivity reached at distal sites, a proximal stimulus had to traverse a longer chord of skin. Specifically, chords 5.9 times longer on average (range = 5.4-6.2) were required on the proximal forearm than on the index finger pad. This finding suggests that relative directional sensitivity increases sixfold from the proximal forearm to the finger pad. Moreover, relative directional sensitivity on the shoulder was comparable to that observed on the proximal forearm for two of the subjects, and approximately one-half that observed on the proximal forearm for the other two subjects. In addition to such a prominent spatial gradient in relative directional sensitivity, the velocity of stimulus motion at which directional sensitivity was highest increased systematically as the test site was shifted from the finger pad to the proximal forearm. Specifically, the optimal velocity on the finger pad varied among subjects from 1.5 to 9.4 cm/sec (mean = 5.4 cm/sec), and on the proximal forearm from 11.5 to 31.2 cm/sec (mean = 18.6 cm/sec). The optimal velocity on the shoulder was not significantly different from that observed on the proximal forearm. The results suggest that effective and informed clinical testing of patients' capacity to distinguish opposing directions of motion on cutaneous regions that differ in peripheral innervation density requires appreciation of the sensitivities of different skin regions, as well as the unique velocity dependency of direction discrimination at each skin site.     

Changes in lower limb volume in humans during parabolic flight

Variations in gravity [head-to-footacceleration (G_z)] inducehemodynamic alterations as a consequence of changes in hydrostatic pressure gradients. To estimate the contribution of the lower limbs toblood pooling or shifting during the different gravity phases of aparabolic flight, we measured instantaneous thigh and calf girths byusing strain-gauge plethysmography in five healthy volunteers. Fromthese circumferential measurements, segmental leg volumes werecalculated at 1, 1.7, and 0 G_z.During hypergravity, leg segment volumes increased by 0.9% for thethigh (P < 0.001) and 0.5% for thecalf (P < 0.001) relative to1-G_z conditions. After suddenexposure to microgravity following hypergravity, leg segment volumeswere reduced by 3.5% for the thigh (P < 0.001) and 2.5% for the calf (P < 0.001) relative to 1.7-G_zconditions. Changes were more pronounced at the upper part of the leg.Extrapolation to the whole lower limb yielded an estimated 60-mlincrease in leg volume at the end of the hypergravity phase and asubsequent 225-ml decrease during microgravity. Although quantitativelyless than previous estimations, these blood shifts may participate inthe hemodynamic alterations observed during hypergravity and weightlessness.

     

Skeletal muscle responses to lower limb suspension in humans.

Eight subjects participated in a 6-wk unilateral lower limb suspension (ULLS) study to determine the influence of reduced weight bearing on human skeletal muscle morphology. The right shoe was outfitted with a platform sole that prevented the left foot from bearing weight while walking with crutches, yet it allowed freedom of movement about the ankle, knee, and hip. Magnetic resonance images pre- and post-ULLS showed that thigh muscle cross-sectional area (CSA) decreased (P less than 0.05) 12% in the suspended left lower limb, whereas right thigh muscle CSA did not change. Likewise, magnetic resonance images collected post-ULLS showed that muscle CSA was 14% smaller (P less than 0.05) in the left than in the right leg. The decrease in muscle CSA of the thigh was due to a twofold greater response of the knee extensors (-16%, P less than 0.05) than knee flexors (-7%, P less than 0.05). The rectus femoris muscle of the knee extensors showed no change in CSA, whereas the three vastus muscles showed similar decreases of approximately 16% (P less than 0.05). The apparent atrophy in the leg was due mainly to reductions in CSA of the soleus (-17%) and gastrocnemius muscles (-26%). Biopsies of the left vastus lateralis pre- and post-ULLS showed a 14% decrease (P less than 0.05) in average fiber CSA. The decrease was evident in both type I (-12%) and II (-15%) fibers. The number of capillaries surrounding the different fiber types was unchanged after ULLS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between blood velocity and conduit artery diameter and the effects of smoking on vascular responsiveness.

Transient changes in arterial diameter in response to transient ischemia-induced changes in arterial blood velocity have been used as an index of vascular health. The purpose of this study was to determine the relationship between blood velocity and diameter in the brachial artery by different methods of increasing blood velocity. Acute cigarette smoking was used with otherwise healthy young occasional smokers to determine the influence of endothelial-nitric oxide pathways on the arterial diameter-blood velocity relationship. Nine nonsmokers and 12 occasional smokers (<1 pack/wk) were tested. Blood flow to the forearm was manipulated to indirectly investigate the relationship between blood velocity and diameter in the brachial artery. Blood flow to forearm was manipulated through the use of 1) 5-min ischemia; 2) handgrip exercise; 3) indirect local heating; and 4) 5-min ischemia plus indirect local heating. A strong relationship was observed between blood velocity and diameter independent of the method used to increase blood velocity (R(2) = 0.89). The mean slope of the velocity-diameter relationship was not different between nonsmokers and occasional smokers who abstained from smoking at least 2 days. Acute smoking did not alter the slope of the velocity-diameter relationship although the mean intercept was decreased as a result of consistent vasoconstriction (7-10%). The mechanisms by which smoking impairs vascular health are largely unknown. These findings differ from previous smoking studies that used chronic and/or heavier smokers. The velocity-diameter relationship appears independent of the method for increasing velocity. Acute smoking in occasional smokers results in vasoconstriction without altering vascular responsiveness. The velocity-diameter relationship may be a useful measure of the progression of vascular disease.     

Exercise-mediated changes in conduit artery wall thickness in humans: role of shear stress

Episodic increases in shear stress have been proposed as a mechanism that induces training-induced adaptation in arterial wall remodeling in humans. To address this hypothesis in humans, we examined bilateral brachial artery wall thickness using high-resolution ultrasound in healthy men across an 8-wk period of bilateral handgrip training. Unilaterally, shear rate was attenuated by cuff inflation around the forearm to 60 mmHg. Grip strength, forearm volume, and girth improved similarly between the limbs. Acute bouts of handgrip exercise increased shear rate (P < 0.005) in the noncuffed limb, whereas cuff inflation successfully decreased exercise-induced increases in shear. Brachial blood pressure responses similarly increased during exercise in both the cuffed and noncuffed limbs. Handgrip training had no effect on baseline brachial artery diameter, blood flow, or shear rate but significantly decreased brachial artery wall thickness after 6 and 8 wk (ANOVA, P < 0.001) and wall-to-lumen ratio after week 8 (ANOVA, P = 0.005). The magnitude of decrease in brachial artery wall thickness and wall-to-lumen ratio after exercise training was similar in the noncuffed and cuffed arms. These results suggest that exercise-induced changes in shear rate are not obligatory for arterial wall remodeling during a period of 8 wk of exercise training in healthy humans.     

Mechanical interaction between neighboring muscles in human upper limb: Evidence for epimuscular myofascial force transmission in humans

To confirm the existence of epimuscular myofascial force transmission in humans, this study examined if manipulating joint angle to stretch the muscle can alter the shear modulus of a resting adjacent muscle, and whether there are regional differences in this response. The biceps brachii (BB: manipulated muscle) and the brachialis (BRA: resting adjacent muscle) were deemed suitable for this study because they are neighboring, yet have independent tendons that insert onto different bones. In order to manipulate the muscle length of BB only, the forearm was passively set at supination, neutral, and pronation positions. For thirteen healthy young adult men, the shear modulus of BB and BRA was measured with shear-wave elastography at proximal and distal muscle regions for each forearm position and with the elbow joint angle at either 100° or 160°. At both muscle regions and both elbow positions, BB shear modulus increased as the forearm was rotated from a supinated to pronated position. Conversely, BRA shear modulus decreased as function of forearm position. The effect of forearm position on shear modulus was most pronounced in the distal muscle region when the elbow was at 160°. The observed alteration of shear modulus of the resting adjacent muscle indicates that epimuscular myofascial force transmission is present in the human upper limb. Consistent with this assertion, we found that the effect of muscle length on shear modulus in both muscles was region-dependent. Our results also suggest that epimuscular myofascial force transmission may be facilitated at stretched muscle lengths.     

Effects of upper or lower airway anesthesia on hypercapnic ventilation in humans

To evaluate the contribution of vagal airway receptors to ventilatory control during hypercapnia, we studied 11 normal humans. Airway receptor block was induced by inhaling an aerosol of lidocaine; a preferential upper oropharyngeal block was also induced in a subgroup by gargling a solution of the anesthetic. Inhalation of lidocaine aerosol adequate to increase cough threshold, as measured by citric acid, did not change the ventilatory response to CO2, ratio of the change in minute ventilation to change in alveolar PCO2 (delta VI/delta PACO2), compared with saline control. Breathing pattern at mean CO2-stimulated ventilation of 25 l/min showed significantly decreased respiratory frequency, increased tidal volume, and prolonged inspiratory time compared with saline. Resting breathing pattern also showed significantly increased tidal volume and inspiratory time. In nine of the same subjects gargling a lidocaine solution adequate to extinguish gag response without altering cough threshold did not change delta VI/delta PACO2 or ventilatory pattern during CO2-stimulated or resting ventilation compared with saline. These results suggest that lower but not upper oropharyngeal vagal airway receptors modulate breathing pattern during hypercapnic as well as resting ventilation but do not affect delta VI/delta PACO2.     

Discrepancy between SEPs directly recorded from the dorsal column nuclei following upper and lower limb stimulation in patients with syringomyelia

Somatosensory evoked potentials (SEPs) in response to electrical stimulation of the median nerve (MN) and posterior tibial nerve (PTN) were studied in 2 patients with syringomyelia. Intraoperative recordings were made from the surface of the dorsal column nuclei as well as from the scalp. Following MN stimulation, there was a preservation of scalp-recorded P9, P11, P13 and N20, however, there was an absence of spinal N13-P13. The dorsal column SEPs to MN stimulation were normal, characterized by a major negativity (N1), preceded by a small positivity (P1) and followed by a large positivity (P2). On the other hand, there was little or no cortical response (P37) to PTN stimulation. The dorsal column SEPs to PTN stimulation showed a disappearance of the normal P1′-N1′-P2′ configuration, being replaced by a series of small spiky waves. The syringomyelic cavity may have thus compressed the gracile dorsal column which courses more medially than the cuneate pathway, causing desynchronization of the dorsal column SEPs. These findings suggest that dorsal column pathway arising from the lower limb is more vulnerable than that from the upper limb when a cervical syrinx is present.     

Exercise training improves conduit vessel function in patients with coronary artery disease.

It is well established that endothelial dysfunction is present in coronary artery disease (CAD), although few studies have determined the effect of training on peripheral conduit vessel function in patients with CAD. A randomized, crossover design determined the effect of 8 wk of predominantly lower limb, combined aerobic and resistance training, in 10 patients with treated CAD. Endothelium-dependent dilation of the brachial artery was determined, by using high-resolution vascular ultrasonography, from flow-mediated vasodilation (FMD) after ischemia. Endothelium-independent vasodilation was measured after administration of glyceryl trinitrate (GTN). Baseline function was compared with that of 10 control subjects. Compared with matched healthy control subjects, FMD and GTN responses were significantly impaired in the untrained CAD patients [3.0 +/- 0.8 (SE) vs. 5.8 +/- 0.8% and 14.5 +/- 1.9 vs. 20.4 +/- 1.5%, respectively; both P < 0.05]. Training significantly improved FMD in the CAD patients (from 3.0 +/- 0.8 to 5.7 +/- 1.1%; P < 0.05) but not responsiveness to GTN (14.5 +/- 1.9 vs. 12.1 +/- 1.4%; P = not significant). Exercise training improves endothelium-dependent conduit vessel dilation in subjects with CAD, and the effect, evident in the brachial artery, appears to be generalized rather than limited to vessels of exercising muscle beds. These results provide evidence for the benefit of exercise training, as an adjunct to routine therapy, in patients with a history of CAD.     

Relationship in humans between spontaneously chosen crank rate and power output during upper body exercise at different levels of intensity

The aim of this study was to assess the relationship between spontaneously chosen crank rate (SCCR) and power output during two upper body exercise tests: firstly, an incremental maximal aerobic power test (T1), with an initial intensity of 50 W followed by 15-W increases at each subsequent 90-s stage and secondly, a test (T2) with consecutive exercise periods set at 50%, 60%, 70%, 80%, 110% and 120% of maximal power (Pmax) separated by passive recovery periods. Eight nationally and internationally ranked kayakers, aged 20 (SD 2) years, performed the tests. During both T1 and T2, mean SCCR values were correlated (r = 1) and increased significantly (P < 0.05) in association with the increases in power output. The finding that the subjects consistently increased their crank rate as the power output increased in different tests, i.e. at submaximal, maximal and supramaximal intensities, strongly suggests that SCCR depended on power output and not on the type of exercise (incremental or rectangular exercise). Moreover, the equation relating crank rate and power output determined from T1 suggests that it may be used to predict the crank rate which will be chosen in upper body exercise, whatever the intensity. Finally, the results of testing at 110% and 120% of Pmax would suggest that a high crank rate (>90 rpm) should be used during the test procedure using supramaximal exercises where accumulated oxygen deficit is calculated, and more particularly when exercise is performed using the upper body.     

Cold induced vasodilatation and cardiovascular responses in humans during cold water immersion of various upper limb areas

To study the physiological responses induced by immersing in cold water various areas of the upper limb, 20 subjects immersed either the index finger (T1), hand (T2) or forearm and hand (T3) for 30 min in 5°C water followed by a 15-min recovery period. Skin temperature of the index finger, skin blood flow (Q_sk) measured by laser Doppler flowmetry, as well as heart rate (HR) and mean arterial blood pressure (ˉBP_a) were all monitored during the test. Cutaneous vascular conductance (CVC) was calculated as Q_sk / ˉBP_a. Cold induced vasodilatation (CIVD) indices were calculated from index finger skin temperature and CVC time courses. The results showed that no differences in temperature, CVC or cardiovascular changes were observed between T2 and T3. During T1, CIVD appeared earlier compared to T2 and T3 [5.90 (SEM 0.32) min in T1 vs 7.95 (SEM 0.86) min in T2 and 9.26 (SEM 0.78) min in T3, P < 0.01]. The HR was unchanged in T1 whereas it increased significantly at the beginning of T2 and T3 [+13 (SEM 2) beats · min⁻¹ in T2 and +15 (SEM 3) beats · min⁻¹ in T3, P < 0.01] and then decreased at the end of the immersion [−12 (SEM 3) beats · min⁻¹ in T2, and −15 (SEM 3) beats · min⁻¹ in T3, P < 0.01]. Moreover, ˉBP_aincreased at the beginning of T1 but was lower than in T2 and T3 [+9.3 (SEM 2.5) mmHg in T1, P < 0.05;  +20.6 (SEM 2.6) mmHg and 26.5 (SEM 2.8) mmHg in T2 and T3, respectively, P < 0.01]. The rewarming during recovery was faster and higher in T1 compared to T2 and T3. These results showed that general and local physiological responses observed during an upper limb cold water test differed according to the area immersed. Index finger cooling led to earlier and faster CIVD without significant cardiovascular changes, whereas hand or forearm immersion led to a delayed and slower CIVD with a bradycardia at the end of the test. Accepted: 26 November 1996