Regional cerebral artery mean flow velocity and blood flow during dynamic exercise in humans.

Transcranial Doppler ultrasound-determined middle (MCA) and anterior (ACA) cerebral artery mean flow velocities (Vmean) and pulsatility indexes (PI) were measured during "no-load" [21, 60, and 102 revolutions/min (rpm)] and loaded cycling (30, 60, and 149 W) at approximately 60 rpm. At rest Vmean MCA was 51 (36-55) cm/s (median and range; n = 10) and Vmean ACA was 41 (36-49) cm/s (n = 7; P < 0.05). With no load on the cycle Vmean MCA increased 4 (2-36), 10 (0-47), and 27% (4-58) (P < 0.05) at the three pedaling frequencies, respectively; arterial PCO2 (PaCO2) remained constant. During loaded cycling the increases were 19 (6-42), 25 (2-45), and 32% (12-67) (P < 0.01), respectively, with only a minimal change in PaCO2. No significant changes were observed in Vmean ACA. Changes in Vmean MCA were similar to those recorded by the initial slope index (ISI) of the 133Xe clearance method (n = 11), which in turn were smaller than increases recorded by the fast-compartment flow. PI ACA followed PI MCA during no-load as well as loaded exercise and increased with work rate, perhaps reflecting an increase in pulse pressure from 56 (48-63) mmHg at rest to 109 (88-123) mmHg at 149 W (P < 0.01). Data demonstrate a graded increase in regional cerebral perfusion during dynamic exercise corresponding to the MCA territory.     

Cardiovascular responses to static and dynamic contraction during comparable workloads in humans

Previous studies suggest that the blood pressure response to static contraction is greater than that caused by dynamic exercise. In anesthetized cats, however, pressor responses to electrically induced static and dynamic contraction of the same muscle group are similar during equivalent workloads and peak tension development [i.e., similar tension-time index (TTI)]. To determine if the same relationship exists in humans, where contraction is voluntary and central command is present, dynamic (180 s; 1/s) and static (90 s) contractions at 30% of maximal voluntary contraction (MVC) were performed. Dynamic contraction also was repeated at the same TTI for 90 s at 60% MVC. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), MAP during postexercise arterial occlusion (an index of the metaboreceptor-induced activation of the exercise pressor reflex), and relative perceived exertion (RPE) (an index of central command) were assessed. No differences in these variables were found between static and dynamic contraction at a tension of 30% MVC. During dynamic contraction at 60% MVC, changes in MAP (16 +/- 3 vs. 19 +/- 4 mmHg) and absolute HR (92 +/- 6 vs. 69 +/- 5 beats/min), CO (7.9 +/- 0.4 vs. 6.3 +/- 0.3 l/min), RPE (16 +/- 1 vs. 13 +/- 1), and MAP during postexercise arterial occlusion (115 +/- 3 vs. 100 +/- 4 mmHg) were greater than during static contraction (P < 0.05). Thus increases in MAP and HR, activation of central command, and muscle metabolite-induced stimulation of the exercise pressor reflex during static and dynamic contraction in humans seem to be similar when peak tension and TTI are equal. Augmented responses to dynamic contraction at 60% MVC are likely related to greater activation of these two mechanisms.     

Gadolinium does not blunt the cardiovascular responses at the onset of voluntary static exercise in cats: a predominant role of central command

The cardiovascular adaptation at the onset of voluntary static exercise is controlled by the autonomic nervous system. Two neural mechanisms are responsible for the cardiovascular adaptation: one is central command descending from higher brain centers, and the other is a muscle mechanosensitive reflex from activation of mechanoreceptors in the contracting muscles. To examine which mechanism played a major role in producing the initial cardiovascular adaptation during static exercise, we studied the effect of intravenous administration of gadolinium (55 micromol/kg), a blocker of stretch-activated ion channels, on the increases in heart rate (HR) and mean arterial blood pressure (MAP) at the onset of voluntary static exercise (pressing a bar with a forelimb) in conscious cats. HR increased by 31 +/- 5 beats/min and MAP increased by 15 +/- 1 mmHg at the onset of voluntary static exercise. Gadolinium affected neither the baseline values nor the initial increases of HR and MAP at the onset of exercise, although the peak force applied to the bar tended to decrease to 65% of the control value before gadolinium. Furthermore, we examined the effect of gadolinium on the reflex responses in HR and MAP (18 +/- 7 beats/min and 30 +/- 6 mmHg, respectively) during passive mechanical stretch of a forelimb or hindlimb in anesthetized cats. Gadolinium significantly blunted the passive stretch-induced increases in HR and MAP, suggesting that gadolinium blocks the stretch-activated ion channels and thereby attenuates the reflex cardiovascular responses to passive mechanical stretch of a limb. We conclude that the initial cardiovascular adaptation at the onset of voluntary static exercise is predominantly induced by feedforward control of central command descending from higher brain centers but not by a muscle mechanoreflex.     

Differential contribution of central command to the cardiovascular responses during static exercise of ankle dorsal and plantar flexion in humans

To examine whether central command contributes differently to the cardiovascular responses during voluntary static exercise engaged by different muscle groups, we encouraged healthy subjects to perform voluntary and electrically evoked involuntary static exercise of ankle dorsal and plantar flexion. Each exercise was conducted with 25% of the maximum voluntary force of the right ankle dorsal and plantar flexion, respectively, for 2 min. Heart rate (HR) and mean arterial blood pressure (MAP) were recorded, and stroke volume, cardiac output (CO), and total peripheral resistance were calculated. With voluntary exercise, HR, MAP, and CO significantly increased during dorsal flexion (the maximum increase, HR: 12 ± 2.3 beats/min; MAP: 14 ± 2.0 mmHg; CO: 1 ± 0.2 l/min), whereas only MAP increased during plantar flexion (the maximum increase, 6 ± 2.0 mmHg). Stroke volume and total peripheral resistance were unchanged throughout the two kinds of voluntary static exercise. With involuntary exercise, there were no significant changes in all cardiovascular variables, irrespective of dorsal or plantar flexion. Furthermore, before the force onset of voluntary static exercise, HR and MAP started to increase without muscle contraction, whereas they had no significant changes with involuntary exercise at the moment. The present findings indicate that differential contribution of central command is responsible for the different cardiovascular responses to static exercise, depending on the strength of central control of the contracting muscle.     

Muscle pump and central command during recovery from exercise in humans.

We sought to determine the relative contributions of cessation of skeletal muscle pumping and withdrawal of central command to the rapid decrease in arterial pressure during recovery from exercise. Twelve healthy volunteers underwent three exercise sessions, each consisting of a warm-up, 3 min of cycling at 60% of maximal heart rate, and 5 min of one of the following recovery modes: seated (inactive), loadless pedaling (active), and passive cycling. Mean arterial pressure (MAP), cardiac output, thoracic impedance, and heart rate were measured. When measured 15 s after exercise, MAP decreased less (P < 0.05) during the active (-3 +/- 1 mmHg) and passive (-6 +/- 1 mmHg) recovery modes than during inactive (-18 +/- 2 mmHg) recovery. These differences in MAP persisted for the first 4 min of recovery from exercise. Significant maintenance of central blood volume (thoracic impedance), stroke volume, and cardiac output paralleled the maintenance of MAP during active and passive conditions during 5 min of recovery. These data indicate that engaging the skeletal muscle pump by loadless or passive pedaling helps maintain MAP during recovery from submaximal exercise. The lack of differences between loadless and passive pedaling suggests that cessation of central command is not as important.     

Changes in regional blood volume and blood flow during static handgrip

Increased blood pressure (BP) and heart rate during exercise characterizes the exercise pressor reflex. When evoked by static handgrip, mechanoreceptors and metaboreceptors produce regional changes in blood volume and blood flow, which are incompletely characterized in humans. We studied 16 healthy subjects aged 20-27 yr using segmental impedance plethysmography validated against dye dilution and venous occlusion plethysmography to noninvasively measure changes in regional blood volumes and blood flows. Static handgrip while in supine position was performed for 2 min without postexercise ischemia. Measurements of heart rate and BP variability and coherence analyses were used to examine baroreflex-mediated autonomic effects. During handgrip exercise, systolic BP increased from 120 +/- 10 to 148 +/- 14 mmHg, whereas heart rate increased from 60 +/- 8 to 82 +/- 12 beats/min. Heart rate variability decreased, whereas BP variability increased, and transfer function amplitude was reduced from 18 +/- 2 to 8 +/- 2 ms/mmHg at low frequencies of approximately 0.1 Hz. This was associated with marked reduction of coherence between BP and heart rate (from 0.76 +/- 0.10 to 0.26 +/- 0.05) indicative of uncoupling of heart rate regulation by the baroreflex. Cardiac output increased by approximately 18% with a 4.5% increase in central blood volume and an 8.5% increase in total peripheral resistance, suggesting increased cardiac preload and contractility. Splanchnic blood volume decreased reciprocally with smaller decreases in pelvic and leg volumes, increased splanchnic, pelvic and calf peripheral resistance, and evidence for splanchnic venoconstriction. We conclude that the exercise pressor reflex is associated with reduced baroreflex cardiovagal regulation and driven by increased cardiac output related to enhanced preload, cardiac contractility, and splanchnic blood mobilization.     

Role of cardiopulmonary baroreflexes during dynamic exercise

To examine the role of cardiopulmonary (CP) mechanoreceptors in the regulation of arterial blood pressure during dynamic exercise in humans, we measured mean arterial pressure (MAP), cardiac output (Q), and forearm blood flow (FBF) during mild cycle ergometer exercise (77 W) in 14 volunteers in the supine position with and without lower-body negative pressure (LBNP). During exercise, MAP averaged 103 +/- 2 mmHg and was not altered by LBNP (-10, -20, or -40 mmHg). Steady-state Q during exercise was reduced from 10.2 +/- 0.5 to 9.2 +/- 0.5 l/min (P less than 0.05) by application of -10 mmHg LBNP, whereas heart rate (97 +/- 3 beats/min) was unchanged. MAP was maintained during -10 mmHg LBNP by an increase in total systemic vascular resistance (TSVR) from 10.3 +/- 0.5 to 11.4 +/- 0.6 U and forearm vascular resistance (FVR) from 17.5 +/- 1.9 to 23.3 +/- 2.6 U. The absence of a reflex tachycardia or reduction in arterial pulse pressure during -10 mmHg LBNP supports the hypothesis that the increase in TSVR and FVR results primarily from the unloading of CP mechanoreceptors. Because CP mechanoreceptor unloading during exercise stimulates reflex circulatory adjustments that act to defend the elevated MAP, we conclude that the elevation in MAP during exercise is regulated and not merely the consequence of differential changes in Q and TSVR. In addition, a major portion of the reduction in FBF in our experimental conditions occurs in the cutaneous circulation. As such, these data support the hypothesis that CP baroreflex control of cutaneous vasomotor tone is preserved during mild dynamic exercise.     

Muscle metaboreflex control of coronary blood flow

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF) and vascular conductance (CVC) in conscious, chronically instrumented dogs during treadmill exercise ranging from mild to severe workloads. Metaboreflex responses were also observed during mild exercise with constant heart rate (HR) of 225 beats/min and beta(1)-adrenergic receptor blockade to attenuate the substantial reflex increases in cardiac work. The muscle metaboreflex was activated via graded partial occlusion of hindlimb blood flow. During mild exercise, with muscle metaboreflex activation, hindlimb ischemia elicited significant reflex increases in mean arterial pressure (MAP), HR, and cardiac output (CO) (+39.0 +/- 5.2 mmHg, +29.9 +/- 7.7 beats/min, and +2.0 +/- 0.4 l/min, respectively; all changes, P < 0.05). CBF increased from 51.9 +/- 4.3 to 88.5 +/- 6.6 ml/min, (P < 0.05), whereas no significant change in CVC occurred (0.56 +/- 0.06 vs. 0.59 +/- 0.05 ml. min(-1). mmHg(-1); P > 0.05). Similar responses were observed during moderate exercise. In contrast, with metaboreflex activation during severe exercise, no further increases in CO or HR occurred, the increases in MAP and CBF were attenuated, and a significant reduction in CVC was observed (1.00 +/- 0.12 vs. 0.90 +/- 0.13 ml. min(-1). mmHg(-1); P < 0.05). Similarly, when the metaboreflex was activated during mild exercise with the rise in cardiac work lessened (via constant HR and beta(1)-blockade), no increase in CO occurred, the MAP and CBF responses were attenuated (+15.6 +/- 4.5 mmHg, +8.3 +/- 2 ml/min), and CVC significantly decreased from 0.63 +/- 0.11 to 0.53 +/- 0.10 ml. min(-1). mmHg(-1). We conclude that the muscle metaboreflex induced increases in sympathetic nerve activity to the heart functionally vasoconstricts the coronary vasculature.     

Muscle mechanoreceptor sensitivity in heart failure

Prior work in animals suggests that muscle mechanoreceptor control of sympathetic activation (MSNA) during exercise in heart failure (HF) is heightened and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether 1) muscle mechanoreceptor control of MSNA is enhanced in HF patients and 2) lactic acid sensitizes muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in healthy humans and patients with HF. Dichloroacetate (DCA), which reduces the production of lactic acid, or saline control was infused in 12 patients with HF and 13 controls during RHG. MSNA was recorded (microneurography). After saline was administered and during exercise thereafter, MSNA increased earlier in HF compared with controls, consistent with baseline-heightened mechanoreceptor sensitivity. In both HF and controls, MSNA increased during the 3-min exercise protocol, consistent with further sensitization of muscle mechanoreceptors by metabolic by-product(s). During posthandgrip circulatory arrest, MSNA returned rapidly to baseline levels, excluding the muscle metaboreceptors as mediators of the sympathetic excitation during RHG. To isolate muscle mechanoreceptors from central command, we utilized passive exercise in 8 HF and 11 controls, and MSNA was recorded. MSNA increased significantly during passive exercise in HF but not in controls. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in healthy humans, and this muscle mechanoreceptor control is augmented further in HF. Neither lactate generation nor the fall in pH during RHG plays a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli resulting in exaggerated early increases in MSNA.     

Autonomic and vascular responses to reduced limb perfusion.

The purpose of this study was to examine hemodynamic responses to graded muscle reflex engagement in human subjects. We studied seven healthy human volunteers [24 +/- 2 (SE) yr old; 4 men, 3 women] performing rhythmic handgrip exercise [40% maximal voluntary contraction (MVC)] during ambient and positive pressure exercise (+10 to +50 mmHg in 10-mmHg increments every minute). Muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and mean blood velocity were recorded. Plasma lactate, hydrogen ion concentration, and oxyhemoglobin saturation were measured from venous blood. Ischemic exercise resulted in a greater rise in both MSNA and MAP vs. nonischemic exercise. These heightened autonomic responses were noted at +40 and +50 mmHg. Each level of positive pressure was associated with an immediate fall in flow velocity and forearm perfusion pressure. However, during each minute, perfusion pressure increased progressively. For positive pressure of +10 to +40 mmHg, this was associated with restoration of flow velocity. However, at +50 mmHg, flow was not restored. This inability to restore flow was seen at a time when the muscle reflex was clearly engaged (increased MSNA). We believe that these findings are consistent with the hypothesis that before the muscle reflex is clearly engaged, flow to muscle is enhanced by a process that raises perfusion pressure. Once the muscle reflex is clearly engaged and MSNA is augmented, flow to muscle is no longer restored by a similar rise in perfusion pressure, suggesting that active vasoconstriction within muscle is occurring at +50 mmHg.     

Hemodynamic responses to static and dynamic muscle contractions at equivalent workloads

We tested the hypothesis that static contraction causes greater reflex cardiovascular responses than dynamic contraction at equivalent workloads [i.e., same tension-time index (TTI), holding either contraction time or peak tension constant] in chloralose-anesthetized cats. When time was held constant and tension was allowed to vary, dynamic contraction of the hindlimb muscles evoked greater increases (means +/- SE) in mean arterial pressure (MAP; 50 +/- 7 vs. 30 +/- 5 mmHg), popliteal blood velocity (15 +/- 3 vs. 5 +/- 1 cm/s), popliteal venous PCO(2) (15 +/- 3 vs. 3 +/- 1 mmHg), and a greater decrease in popliteal venous pH (0.07 +/- 0.01 vs. 0.03 +/- 0.01), suggesting greater metabolic stimulation during dynamic contraction. Similarly, when peak tension was held constant and time was allowed to vary, dynamic contraction evoked a greater increase in blood velocity (13 +/- 1 vs. -1 +/- 1 cm/s) without causing any differences in other variables. To investigate the reflex contribution of mechanoreceptors, we stretched the hindlimb dynamically and statically at the same TTI. A larger reflex increase in MAP during dynamic stretch (32 +/- 8 vs. 24 +/- 6 mmHg) was observed when time was held constant, indicating greater mechanoreceptor stimulation. However, when peak tension was held constant, there were no differences in the reflex cardiovascular response to static and dynamic stretch. In conclusion, at comparable TTI, when peak tension is variable, dynamic muscle contraction causes larger cardiovascular responses than static contraction because of greater chemical and mechanical stimulation. However, when peak tensions are equivalent, static and dynamic contraction or stretch produce similar cardiovascular responses.     

Cerebral blood flow during static exercise in humans

Cerebral blood flow (CBF) was determined in humans at rest and during four consecutive unilateral static contractions of the knee extensors. Each contraction was maintained for 3 min 15 s with the subjects in a semisupine position. The contractions corresponded to 8, 16, 24, and 32% of the maximal voluntary contraction (MVC) and utilized alternate legs. CBF (measured by the 133Xe clearance technique) was expressed by a noncompartmental flow index (ISI). Heart rate and mean arterial pressure increased from resting values of 73 (55-80) beats/min and 88 (74-104) mmHg to 106 (86-138) beats/min and 124 (102-146) mmHg, respectively (P less than 0.0005), during the contraction at 32% MVC. Arterial PCO2 and central venous pressure did not change. Corrected to the average resting PCO2, CBF during control was 55 (35-73) ml.100 g-1.min-1 and remained constant during contractions. Cerebral vascular resistance increased from 1.5 (1.0-2.2) to 2.4 (1.4-3.0) mmHg. 100 g.min.ml-1 (P less than 0.025) at 32% of MVC. There was no difference in CBF between the two hemispheres at rest or during exercise. In contrast to dynamic leg exercise, static leg exercise is not associated with an increase in global CBF when measured by the 133Xe clearance technique.     

Cardiovascular responses to voluntary and nonvoluntary static exercise in humans.

We have measured the cardiovascular responses during voluntary and nonvoluntary (electrically induced) one-leg static exercise in humans. Eight normal subjects were studied at rest and during 5 min of static leg extension at 20% of maximal voluntary contraction performed voluntarily and nonvoluntarily in random order. Heart rate (HR), mean arterial pressure (MAP), and cardiac output (CO) were determined, and peripheral vascular resistance (PVR) and stroke volume (SV) were calculated. HR increased from approximately 65 +/- 3 beats/min at rest to 80 +/- 4 and 78 +/- 6 beats/min (P < 0.05), and MAP increased from 83 +/- 6 to 103 +/- 6 and 105 +/- 6 mmHg (P < 0.05) during voluntary and nonvoluntary contractions, respectively. CO increased from 5.1 +/- 0.7 to 6.0 +/- 0.8 and 6.2 +/- 0.8 l/min (P < 0.05) during voluntary and nonvoluntary contractions, respectively. PVR and SV did not change significantly during voluntary or nonvoluntary contractions. Thus the cardiovascular responses were not different between voluntary and electrically induced contractions. These results suggest that the increases in CO, HR, SV, MAP, and PVR during 5 min of static contractions can be elicited without any contribution from a central neural mechanism (central command). However, central command could still have an important role during voluntary static exercise.     

Exercise pressor reflex in decerebrate and anesthetized rats

I investigated whether muscular contraction evokes cardiorespiratory increases (exercise pressor reflex) in alpha-chloralose- and chloral hydrate-anesthetized and precollicular, midcollicular, and postcollicular decerebrated rats. Mean arterial pressure (MAP), heart rate (HR), and minute ventilation (Ve) were recorded before and during 1-min sciatic nerve stimulation, which induced static contraction of the triceps surae muscles, and during 1-min stretch of the calcaneal tendon, which selectively stimulated mechanosensitive receptors in the muscles. Anesthetized rats showed various patterns of MAP response to both stimuli, i.e., biphasic, depressor, pressor, and no response. Sciatic nerve stimulation to muscle in precollicular decerebrated rats always evoked spontaneous running, so the exercise pressor reflex was not determined from these preparations. None of the postcollicular decerebrated rats showed a MAP response or spontaneous running. Midcollicular decerebrated rats consistently showed biphasic blood pressure response to both stimulations. The increases in MAP, HR, and Ve were related to the tension developed. The static contractions in midcollicular decerebrated rats (381 +/- 65 g developed tension) significantly increased MAP, HR, and Ve from 103 +/- 12 to 119 +/- 24 mmHg, from 386 +/- 30 to 406 +/- 83 beats/min, and from 122 +/- 7 to 133 +/- 25 ml/min, respectively. After paralysis, sciatic nerve stimulation had no effect on MAP, HR, or Ve. These results indicate that the midcollicular decerebrated rat can be a model for the study of the exercise pressor reflex.     

Muscle oxygen extraction and perfusion heterogeneity during continuous and intermittent static exercise.

The purpose of this study was to compare the effects of intermittent and continuous static exercise on muscle perfusion, perfusion heterogeneity, and oxygen extraction. Perfusion and oxygen uptake of quadriceps femoris muscle were measured in 10 healthy men by using positron emission tomography and [(15)O]H(2)O and [(15)O]O(2) first during intermittent static exercise [10% of maximal static force (MSF)] and thereafter during continuous static exercise at the same tension-time level (5% static; 5% of MSF). In 4 of these subjects, perfusion was measured during continuous static exercise with 10% of MSF (10% continuous) instead of the second [(15)O]O(2) measurement. Muscle oxygen consumption was similar during intermittent and 5% continuous, but muscle perfusion was significantly higher during 5% continuous. Consequently, muscle oxygen extraction fraction was lower during 5% continuous. Perfusion was also more heterogeneous during 5% continuous. When exercise intensity was doubled during continuous static exercise (from 5% continuous to 10% continuous), muscle perfusion increased markedly. These results suggest that continuous, low-intensity static exercise decreases muscle oxygen extraction and increases muscle perfusion and its heterogeneity compared with intermittent static exercise at the same relative exercise intensity.     

Increases in intramuscular pressure raise arterial blood pressure during dynamic exercise.

This investigation was designed to determine the role of intramuscular pressure-sensitive mechanoreceptors and chemically sensitive metaboreceptors in affecting the blood pressure response to dynamic exercise in humans. Sixteen subjects performed incremental (20 W/min) cycle exercise to fatigue under four conditions: control, exercise with thigh cuff occlusion of 90 Torr (Cuff occlusion), exercise with lower body positive pressure (LBPP) of 45 Torr, and a combination of thigh cuff occlusion and LBPP (combination). Indexes of central command (heart rate, oxygen uptake, ratings of perceived exertion, and electromyographic activity), cardiac output, stroke volume, and total peripheral resistance were not significantly different between the four conditions. Mechanical stimulation during LBPP and combination conditions resulted in significant elevations in intramuscular pressure and mean arterial pressure from control at rest and throughout the incremental exercise protocol (P < 0.05). Conversely, there existed no significant changes in mean arterial pressure when the metaboreflex was stimulated by cuff occlusion. These findings suggest that under normal conditions the mechanoreflex is tonically active and is the primary mediator of exercise pressor reflex-induced alterations in arterial blood pressure during submaximal dynamic exercise in humans.     

Abnormal neurovascular control during exercise is linked to heart failure severity

The purpose of this study was to determine if abnormalities of sympathetic neural and vascular control are present in mild and/or severe heart failure (HF) and to determine the underlying afferent mechanisms. Patients with severe HF, mild HF, and age-matched controls were studied. Muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) in the nonexercising arm were measured during mild and moderate static handgrip. MSNA during moderate handgrip was higher at baseline and throughout exercise in severe HF vs. mild HF (peak MSNA 67 +/- 3 vs. 54 +/- 3 bursts/min, P < 0.0001) and higher in mild HF vs. controls (33 +/- 3 bursts/min, P < 0.0001), but the change in MSNA was not different between the groups. The change in FVR was not significantly different between the three groups during static exercise. During isolation of muscle metaboreceptors, MSNA and blood pressure remained elevated in normal controls and mild HF but not in severe HF. During mild handgrip, the increase in MSNA was exaggerated in severe HF vs. controls and mild HF, in whom MSNA did not increase. In summary, the increase in MSNA during static exercise in severe HF appears to be attributable to exaggerated central command or muscle mechanoreceptor control, not muscle metaboreceptor control.     

Cerebral blood flow responses to changes in oxygen and carbon dioxide in humans

This study characterized cerebral blood flow (CBF) responses in the middle cerebral artery to PCO2 ranging from 30 to 60 mmHg (1 mmHg = 133.322 Pa) during hypoxia (50 mmHg) and hyperoxia (200 mmHg). Eight subjects (25 +/- 3 years) underwent modified Read rebreathing tests in a background of constant hypoxia or hyperoxia. Mean cerebral blood velocity was measured using a transcranial Doppler ultrasound. Ventilation (VE), end-tidal PCO2 (PETCO2), and mean arterial blood pressure (MAP) data were also collected. CBF increased with rising PETCO2 at two rates, 1.63 +/- 0.21 and 2.75 +/- 0.27 cm x s(-1) x mmHg(-1) (p < 0.05) during hypoxic and 1.69 +/- 0.17 and 2.80 +/- 0.14 cm x s(-1) x mmHg(-1) (p < 0.05) during hyperoxic rebreathing. VE also increased at two rates (5.08 +/- 0.67 and 10.89 +/- 2.55 L min(-1) m mHg(-1) and 3.31 +/- 0.50 and 7.86 +/- 1.43 L x min(-1) x mmHg(-1)) during hypoxic and hyperoxic rebreathing. MAP and PETCO2 increased linearly during both hypoxic and hyperoxic rebreathing. The breakpoint separating the two-component rise in CBF (42.92 +/- 1.29 and 49.00 +/- 1.56 mmHg CO2 during hypoxic and hyperoxic rebreathing) was likely not due to PCO2 or perfusion pressure, since PETCO2 and MAP increased linearly, but it may be related to VE, since both CBF and VE exhibited similar responses, suggesting that the two responses may be regulated by a common neural linkage.     

Muscle metaboreflex modulates the arterial baroreflex dynamic effects on peripheral vascular conductance in humans

We aimed to investigate the interaction between the arterial baroreflex and muscle metaboreflex [as reflected by alterations in the dynamic responses shown by leg blood flow (LBF: by the ultrasound Doppler method), leg vascular conductance (LVC), mean arterial blood pressure (MAP), and heart rate (HR)] in humans. In 12 healthy subjects (10 men and 2 women), who performed sustained 1-min handgrip exercise at 50% maximal voluntary contraction followed immediately by an imposed postexercise muscle ischemia (PEMI), 5-s periods of neck pressure (NP; 50 mmHg) or neck suction (NS; -60 mmHg) were used to evaluate carotid baroreflex function both at rest (Con) and during PEMI. First, the decreases in LVC and LBF and the augmentation of MAP elicited by NP were all greater during PEMI than in Con (DeltaLVC, -1.2 +/- 0.2 vs. -1.9 +/- 0.2 ml.min(-1).mmHg(-1); DeltaLBF, -97.3 +/- 11.2 vs. -177.0 +/- 21.8 ml/min; DeltaMAP, 6.7 +/- 1.2 vs. 11.5 +/- 1.4 mmHg, Con vs. PEMI; each P < 0.05). Second, in Con, NS significantly increased both LVC and LBF (DeltaLVC, 0.9 +/- 0.2 ml.min(-1).mmHg(-1); DeltaLBF, 46.6 +/- 9.8 ml/min; significant change from baseline: each P < 0.05), and, whereas during PEMI no significant increases in LVC and LBF occurred during NS itself (DeltaLVC, 0.2 +/- 0.1 ml.min(-1).mmHg(-1); DeltaLBF, 10.8 +/- 9.6 ml/min; each P > 0.05), a decrease was evident in each parameters at 5 s after the cessation of NS. Third, during PEMI, the decrease in MAP elicited by NS was smaller (DeltaMAP, -8.4 +/- 1.0 vs. -5.8 +/- 0.4 mmHg, Con vs. PEMI; P < 0.05), and it recovered to its initial level more quickly after NS (vs. Con). Finally, however, the HR responses to NS and NP were not different between PEMI and Con. These results suggest that during muscle metaboreflex activation in humans, the arterial baroreflex dynamic effect on peripheral vascular conductance is modulated, as exemplified by 1) an augmentation of the NP-induced LVC decrease, and 2) a loss of the NS-induced LVC increase.     

Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG, and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of postexercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e., wrist dorsiflexion) was performed. The static stretch protocol was also performed during 1) a freely perfused condition, 2) ischemia alone, and 3) PEMI after nonfatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 +/- 74 to 673 +/- 90 U/min, P < 0.01) and mean blood pressure (102 +/- 2 to 106 +/- 2 mmHg, P < 0.001). Static stretch performed under the other three conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased above a certain threshold.