Echo Intensity of Gastrocnemius Is Independently Associated with 6-Minute Walking Distance in Male Patients with Peripheral Arterial Disease.

Background and Objectives: This study aimed to examine the differences in the thickness and echo intensity (EI) of the gastrocnemius muscle measured via ultrasonography between healthy adults and patients with peripheral arterial disease (PAD) and to determine the associations of gastrocnemius thickness (GT) and EI within a 6 min walking distance (6MD) in patients with PAD. Materials and Methods: This cross-sectional study targeted 35 male patients with PAD (mean age, 73.7 years; mean body mass index [BMI], 23.5 kg/m2) and age- and gender-matched 73 male healthy adults (mean age, 73.2 years; mean BMI, 23.3 kg/m2). The gastrocnemius thickness (GT) and EI were measured using ultrasound. Both legs of patients with PAD were classified based on higher and lower ankle brachial pressure index (ABI), and the GTs and EIs with higher and lower ABI were compared with those of healthy adults. Multiple regression analysis incorporated 6MD as a dependent variable and each GT and EI with higher and lower ABI, age, and BMI as independent variables. Results: This study showed that GT was considerably greater in healthy adults than in both legs with higher and lower ABI (median values, 13.3 vs. 11.3 vs. 10.7, p < 0.01), whereas EI was lower in healthy adults than in the lower ABI leg (72.0 vs. 80.8 vs. 83.6, p < 0.05). The 6MD was shown to be substantially related to EI in both legs with higher and lower ABIs (p < 0.01) but not in the GT. Conclusions: In patients with PAD, the GT was lower, and EI was higher than in healthy adults. In addition, EIs in both legs with higher and lower ABIs were independently associated with 6MD in male PAD patients. This study showed that the EI measured via ultrasonography could become an important indicator for treatments for patients with PAD.

Central command suppresses pressor-evoked bradycardia at the onset of voluntary standing up in conscious cats.

NEW FINDINGS: What is the central question of this study? Standing up can cause hypotension and tachycardia. Accumulated evidence poses the simple question, does the cardiac baroreflex operate at the onset of standing up? If the cardiac baroreflex is suppressed, what mechanism is responsible for baroreflex inhibition? What is the main finding and its importance? In cats, we found blunting of cardiac baroreflex sensitivity in the pressor range at the onset of voluntary hindlimb standing, but not of passive hindlimb standing. This finding suggests that central command suppresses pressor-evoked bradycardia at the onset of standing up, probably in advance, to prevent or buffer orthostatic hypotension. ABSTRACT: It remains unclear whether cardiac baroreflex function is preserved or suppressed at the onset of standing up. To answer the question and, if cardiac baroreflex is suppressed, to investigate the mechanism responsible for the suppression, we compared the sensitivity of the arterial cardiac baroreflex at the onset of voluntary and passive hindlimb standing in conscious cats. Cardiac baroreflex sensitivity was estimated from the maximal slope of the baroreflex curve between the responses of systolic arterial blood pressure and heart rate to a brief occlusion of the abdominal aorta. The systolic arterial blood pressure response to standing up without aortic occlusion was greater in the voluntary case than in the passive case. Cardiac baroreflex sensitivity was clearly decreased at the onset of voluntary standing up compared with rest (P = 0.005) and the onset of passive standing up (P = 0.007). The cardiac baroreflex sensitivity at the onset of passive standing up was similar to that at rest (P = 0.909). The findings suggest that central command would transmit a modulatory signal to the cardiac baroreflex system during the voluntary initiation of standing up. Furthermore, the present data tempt speculation on a close relationship between central inhibition of the cardiac baroreflex and the centrally induced tachycardiac response to standing up.

Central modulation of cardiac baroreflex moment-to-moment sensitivity during treadmill exercise in conscious cats.

It remains undetermined whether the cardiac component of the entire arterial baroreflex is blunted even at the onset of low-intensity exercise. We sought to examine the moment-to-moment sensitivity of the cardiac baroreflex during walking at different speeds and the presumed mechanisms responsible for baroreflex modulation in conscious cats. Arterial baroreflex sensitivity for heart rate was estimated from the baroreflex ratio between changes in systolic arterial blood pressure and heart rate and from the slope of the baroreflex curve between the cardiovascular responses to brief occlusion of the abdominal aorta. Treadmill walking was performed for 1 min at three levels of speed (low: 20-30 m/min, moderate: 40 m/min, and high: 50-60 m/min) or for 3 min at the stepwise change of speed (low to high to low transition). Cardiac baroreflex sensitivity was blunted at the onset of walking, irrespective of speed. Thereafter, the blunted cardiac baroreflex sensitivity was restored around 15 s of walking at any speed, while the blunting occurred again at 45 s of high-speed walking. The inhibition of cardiac baroreflex sensitivity also occurred (1) during the speed transition from low to high and (2) at 45 s of high-speed exercise of the stepwise exercise. The blunted cardiac baroreflex sensitivity was restored immediately to the resting level during the speed transition from high to low, despite sustained pressor and tachycardiac responses. Therefore, moment-to-moment modulation of the cardiac baroreflex during exercise would occur in association with motor intention (i.e., exercise onset) and effort (i.e., treadmill speed).

Incremental rate of prefrontal oxygenation determines performance speed during cognitive Stroop test: the effect of ageing.

Cognitive function declines with age. The underlying mechanisms responsible for the deterioration of cognitive performance, however, remain poorly understood. We hypothesized that an incremental rate of prefrontal oxygenation during a cognitive Stroop test decreases in progress of ageing, resulting in a slowdown of cognitive performance. To test this hypothesis, we identified, using multichannel near-infrared spectroscopy, the characteristics of the oxygenated-hemoglobin concentration (Oxy-Hb) responses of the prefrontal cortex to both incongruent Stroop and congruent word-reading test. Spatial distributions of the significant changes in the three components (initial slope, peak amplitude, and area under the curve) of the Oxy-Hb response were compared between young and elderly subjects. The Stroop interference time (as a difference in total periods for executing Stroop and word-reading test, respectively) approximately doubled in elderly as compared to young subjects. The Oxy-Hb in the rostrolateral, but not caudal, prefrontal cortex increased during the Stroop test in both age groups. The initial slope of the Oxy-Hb response, rather than the peak and area under the curve, had a strong correlation with cognitive performance speed. Taken together, it is likely that the incremental rate of prefrontal oxygenation may decrease in progress of ageing, resulting in a decline in cognitive performance.

Central command increases muscular oxygenation of the non-exercising arm at the early period of voluntary one-armed cranking.

This study aimed to examine whether central command increases oxygenation in non-contracting arm muscles during contralateral one-armed cranking and whether the oxygenation response caused by central command differs among skeletal muscles of the non-exercising upper limb. In 13 male subjects, the relative changes in oxygenated-hemoglobin concentration (Oxy-Hb) of the non-contracting arm muscles [the anterior deltoid, triceps brachii, biceps brachii, and extensor carpi radialis (ECR)] were measured during voluntary one-armed cranking (intensity, 35-40% of maximal voluntary effort) and mental imagery of the one-armed exercise for 1 min. Voluntary one-armed cranking increased (P < 0.05) the Oxy-Hb of the triceps, biceps, and ECR muscles to the same extent (15 ± 4% of the baseline level, 17 ± 5%, and 16 ± 4%, respectively). The greatest increase in the Oxy-Hb was observed in the deltoid muscle. Intravenous injection of atropine (10-15 µg/kg) and/or propranolol (0.1 mg/kg) revealed that the increased Oxy-Hb of the arm muscles consisted of the rapid atropine-sensitive and delayed propranolol-sensitive components. Mental imagery of the exercise increased the Oxy-Hb of the arm muscles. Motor-driven passive one-armed cranking had little influence on the Oxy-Hb of the arm muscles. It is likely that central command plays a role in the initial increase in oxygenation in the non-contracting arm muscles via sympathetic cholinergic vasodilatation at the early period of one-armed cranking. The centrally induced increase in oxygenation may not be different among the distal arm muscles but may augment in the deltoid muscle.

Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat.

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade.

Central command generated prior to arbitrary motor execution induces muscle vasodilatation at the beginning of dynamic exercise.

The purpose of this study was to examine the role of central command, generated prior to arbitrary motor execution, in cardiovascular and muscle blood flow regulation during exercise. Thirty two subjects performed 30 s of two-legged cycling or 1 min of one-legged cycling (66 ± 4% and 35% of the maximal exercise intensity, respectively), which was started arbitrarily or abruptly by a verbal cue (arbitrary vs. cued start). We measured the cardiovascular variables during both exercises and the relative changes in oxygenated-hemoglobin concentration (Oxy-Hb) of noncontracting vastus lateralis muscles as index of tissue blood flow and femoral blood flow to nonexercising leg during one-legged cycling. Two-legged cycling with arbitrary start caused a decrease in total peripheral resistance (TPR), which was smaller during the exercise with cued start. The greater reduction of TPR with arbitrary start was also recognized at the beginning of one-legged cycling. Oxy-Hb of noncontracting muscle increased by 3.6 ± 1% (P < 0.05) during one-legged cycling with arbitrary start, whereas such increase in Oxy-Hb was absent with cued start. The increases in femoral blood flow and vascular conductance of nonexercising leg were evident (P < 0.05) at 10 s from the onset of one-legged cycling with arbitrary start, whereas those were smaller or absent with cued start. It is likely that when voluntary exercise is started arbitrarily, central command is generated prior to motor execution and then contributes to muscle vasodilatation at the beginning of exercise. Such centrally induced muscle vasodilatation may be weakened and/or masked in the case of exercise with cued start.

Differential contribution of aortic and carotid sinus baroreflexes to control of heart rate and renal sympathetic nerve activity.

We examined the roles of aortic and carotid sinus baroreceptors in control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in 17 decerebrate rats. The baroreflex curves between the changes in mean arterial blood pressure (MAP) and HR or RSNA in response to intravenous injection of phenylephrine (10-20 µg/kg) or nitroprusside (10 µg/kg) were identified before and following sequential denervation of all four baroafferent nerves. The slope of the MAP-HR curve in the pressor range was decreased (P < 0.05) to 31 ± 7% of the control following denervation of bilateral aortic nerves, whereas it remained substantial (72 ± 10%) following denervation of bilateral carotid sinus nerves. The slope for HR became negligible following complete denervation of all four baroafferent nerves. In contrast, the slope of the MAP-RSNA curve decreased as the sequential baroafferent denervation progressed, irrespective of the denervation order, and it remained well as long as any single baroafferent nerve was intact. The similar influences of sequential baroafferent denervation on the responses of HR and RSNA were observed in the depressor range. Thus, it is likely that aortic and carotid sinus baroreceptors play differential roles in control of HR but they contribute similarly to control of RSNA.

Differential contribution of ACh-muscarinic and ß-adrenergic receptors to vasodilatation in noncontracting muscle during voluntary one-legged exercise.

We have demonstrated the centrally induced cholinergic vasodilatation in skeletal muscle at the early period of voluntary one-legged exercise and during motor imagery in humans. The purpose of this study was to examine whether central command may also cause ß-adrenergic vasodilatation during the exercise and motor imagery. Relative changes in oxygenated hemoglobin concentration (Oxy-Hb) of bilateral vastus lateralis (VL) muscles, as index of tissue blood flow, and femoral blood flow to nonexercising limb were measured during one-legged cycling and mental imagery of the exercise for 1 min before and after propranolol (0.1 mg/kg iv). The Oxy-Hb of noncontracting muscle increased (P < 0.05) at the early period of exercise and the increase was sustained throughout exercise, whereas the Oxy-Hb of contracting muscle increased at the early period but thereafter decreased. We subtracted the Oxy-Hb response with propranolol from the control response in individual subjects to identify the propranolol-sensitive component of the Oxy-Hb response during exercise. In both noncontracting and contracting VL muscles, the increase in Oxy-Hb at the early period of one-legged exercise did not involve a significant propranolol-sensitive component. However, as the exercise proceeded, the propranolol-sensitive component of the Oxy-Hb response was developed during the later period of exercise. Propranolol also failed to affect the initial increases in femoral blood flow and vascular conductance of nonexercising leg but significantly attenuated (P < 0.05) their later increases during exercise. Subsequent atropine (10-15 µg/kg iv) abolished the initial increases in Oxy-Hb of both VL muscles. Mental imagery of the one-legged exercise caused the bilateral increases in Oxy-Hb, which were not altered by propranolol but abolished by subsequent atropine. It is likely that the rapid cholinergic and delayed ß-adrenergic vasodilator mechanisms cooperate to increase muscle blood flow during exercise.

Discharges of aortic and carotid sinus baroreceptors during spontaneous motor activity and pharmacologically evoked pressor interventions.

Our laboratory has demonstrated that the cardiomotor component of aortic baroreflex is temporarily inhibited at the onset of spontaneous motor activity in decerebrate cats, without altering carotid sinus baroreflex. A reason for this dissociation may be attributed to a difference in the responses between aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity. The stimulus-response curves of AoNA and CsNA against mean arterial blood pressure (MAP) were compared between the pressor interventions evoked by spontaneous motor activity and by intravenous administration of phenylephrine or norepinephrine, in which the responses in heart rate (HR) were opposite (i.e., tachycardia vs. baroreflex bradycardia), despite the identical increase in MAP of 34-40 mmHg. In parallel to the pressor response, mean AoNA and CsNA increased similarly by 78-81 and by 88 % of the baseline control, respectively, irrespective of whether the pressor response was evoked by spontaneous motor activity or by a pharmacological intervention. The slope of the stimulus-response curve of the mean AoNA became greater (P < 0.05) during spontaneous motor activity as compared to the pharmacological intervention. On the other hand, the stimulus-response curve of the mean CsNA and its slope were equal (P > 0.05) between the two pressor interventions. Furthermore, the slopes of the stimulus-response curves of both diastolic AoNA and CsNA (defined as the minimal value within a beat) exhibited a greater increase during spontaneous motor activity. All differences in the slopes of the stimulus-response curves were abolished by restraining HR at the intrinsic cardiac frequency. In conclusion, mean mass activities of both aortic and carotid sinus baroreceptors are able to encode the beat-by-beat changes in MAP not only at rest but also during spontaneous motor activity and spontaneous motor activity-related reduction of aortic baroreceptor activity is denied accordingly.

Signal transduction of aortic and carotid sinus baroreceptors is not modified by central command during spontaneous motor activity in decerebrate cats.

Our laboratory has suggested that central command provides selective inhibition of the cardiomotor component of aortic baroreflex at the start of exercise, preserving carotid sinus baroreflex. It is postulated that central command may modify the signal transduction of aortic baroreceptors, so as to decrease aortic baroreceptor input to the cardiovascular centers, and, thereby, can cause the selective inhibition of aortic baroreflex. To test the hypothesis, we directly analyzed the responses in multifiber aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity in decerebrate, paralyzed cats. The increases of 62-104% in mean AoNA and CsNA were found during spontaneous motor activity, in proportion to a rise of 35 ± 3 mmHg (means ± SE) in mean arterial blood pressure (MAP), and had an attenuating tendency by restraining heart rate (HR) at the lower intrinsic frequency of 154 ± 6 beats/min. Brief occlusion of the abdominal aorta was conducted before and during spontaneous motor activity to produce a mechanically evoked increase in MAP and, thereby, to examine the stimulus-response relationship of arterial baroreceptors. Although the sensitivity of the MAP-HR baroreflex curve was markedly blunted during spontaneous motor activity, the stimulus-response relationships of AoNA and CsNA were not influenced by spontaneous motor activity, irrespective of the absence or presence of the HR restraint. Thus, it is concluded that aortic and carotid sinus baroreceptors can code beat-by-beat blood pressure during spontaneous motor activity in decerebrate cats and that central command is unlikely to modulate the signal transduction of arterial baroreceptors.

Evidence for centrally induced cholinergic vasodilatation in skeletal muscle during voluntary one-legged cycling and motor imagery in humans.

We have recently reported that central command contributes to increased blood flow in both noncontracting and contracting vastus lateralis (VL) muscles at the early period of voluntary one-legged cycling. The purpose of this study was to examine whether sympathetic cholinergic vasodilatation mediates the increases in blood flows of both muscles during one-legged exercise. Following intravenous administration of atropine (10 µg/kg), eight subjects performed voluntary 1-min one-legged cycling (at 35% of maximal voluntary effort) and mental imagery of the exercise. The relative concentrations of oxygenated- and deoxygenated-hemoglobin (Oxy- and Deoxy-Hb) in the bilateral VL were measured as an index of muscle tissue blood flow with near-infrared spectroscopy (NIRS). The Oxy-Hb in both noncontracting and contracting VL increased at the early period of one-legged cycling, whereas the Deoxy-Hb did not alter at that period. Atropine blunted (P < 0.05) the Oxy-Hb responses of both VL muscles but did not affect the Deoxy-Hb responses. The time course and magnitude of the atropine-sensitive component in the Oxy-Hb response were quite similar between the noncontracting and contracting VL muscles. With no changes in the Deoxy-Hb and hemodynamics, imagery of one-legged cycling induced the bilateral increases in the Oxy-Hb, which were completely abolished by atropine. In contrast, imagery of a circle (with no relation to exercise) did not alter the NIRS signals, irrespective of the presence or absence of atropine. It is concluded that central command evokes cholinergic vasodilatation equally in bilateral VL muscles during voluntary one-legged cycling and motor imagery.

Central command differentially affects aortic and carotid sinus baroreflexes at the onset of spontaneous motor activity.

Our laboratory has recently demonstrated that central command provides selective inhibition of the cardiomotor component of aortic (AOR) baroreflex during exercise, preserving carotid sinus (CS) baroreflex. To further explore the differential effects of central command on the arterial baroreflexes, we surgically separated the AOR and CS baroreflex systems, to identify the input-output relationship of each baroreflex system using brief occlusion of the abdominal aorta in decerebrate cats. Baroreflex sensitivity for heart rate (HR) was estimated from the baroreflex ratio between the pressor and bradycardia responses during aortic occlusion and from the slope of the baroreflex curve between the changes in mean arterial blood pressure (ΔMAP) and ΔHR. Spontaneous motor activity accompanied the abrupt increases in HR and MAP. When aortic occlusion was given at the onset of spontaneous motor activity, the baroreflex ratio was blunted to 11-25% of the preexercise value in either intact or AOR baroreflex. The slope of the ΔMAP-ΔHR curve was similarly attenuated at the onset of spontaneous motor activity to 11-18% of the slope during the preexercise period. In contrast, in the CS baroreflex, the baroreflex ratio and curve slope were not significantly (P>0.05) altered by spontaneous motor activity. An upward shift of the baroreflex curve appeared at the onset of spontaneous motor activity, irrespective of the intact, AOR, and CS baroreflex conditions. Taken together, it is concluded that central command provides selective inhibition for the cardiomotor limb of the aortic baroreflex at the onset of exercise, which in turn contributes to an instantaneous increase in HR.