Peripheral Resistance Responses Research Articles

Long-duration bed rest augments sympathetic neurovascular responses to simulated orthostatic stress among females

Our understanding of the impact of long-duration head-down bed rest (HDBR) on sympathetic neurovascular regulation during orthostatic stress remains incomplete. Through retrospective analysis of the WISE-2005 long-duration bed rest trial, this study aimed to investigate the impact of 60 days of -6° HDBR on the transduction of integrated muscle sympathetic nerve activity (MSNA; peroneal microneurography) into total peripheral resistance (TPR; Finometer Modelflow) responses during rest and graded lower body negative pressure (LBNP; -20, -30, and -45 mmHg). Signal averaging quantified sympathetic transduction for 12 cardiac cycles (ECG) following integrated MSNA bursts in healthy females ( n = 12; 25-40 years). Mixed-effects modeling and post-hoct-tests assessed the impact of HDBR on sympathetic transduction during rest (5-min) and graded LBNP (3-min per level). Data are presented as mean ± SD. Long-duration HDBR did not affect resting total MSNA (pre-HDBR: 909 ± 368 AU/min, post-HDBR: 910 ± 254 AU/min; p = 0.999). HDBR did not affect total MSNA responses to -20 mmHg LBNP (pre-HDBR: 1430 ± 599 AU/min, post-HDBR: 1823 ± 433 AU/min), -30 mmHg LBNP (pre-HDBR: 1574 ± 549 AU/min, post-HDBR: 1924 ± 587 AU/min), or -45 mmHg LBNP (pre-HDBR: 1950 ± 819 AU/min, post-HDBR: 2328 ± 880 AU/min; p = 0.191). HDBR did not affect resting sympathetic transduction to TPR (pre-HDBR: 0.002 ± 0.16 mmHg/L/min, post-HDBR: -0.091 ± 0.12 mmHg/L/min; p = 0.296). However, HDBR augmented TPR transduction responses to graded LBNP (HDBR-by-LBNP interaction: p = 0.050). Pre-HDBR, TPR transduction responses were unchanged with graded LBNP (all p > 0.05). In contrast, post-HDBR, TPR transduction responses increased progressively with graded LBNP (rest: -0.09 ± 0.12 mmHg/L/min, -20 mmHg: 0.22 ± 0.31 mmHg/L/min, -30 mmHg: 0.30 ± 0.34 mmHg/L/min, -45 mmHg: 0.44 ± 0.12 mmHg/L/min; all p < 0.005). The same effect of HDBR was observed when sympathetic transduction of mean arterial pressure was analyzed (data not shown). These data suggest that long-duration HDBR augments sympathetic neurovascular responses to integrated MSNA bursts during orthostatic stress among females. This work was supported by the Canadian Space Agency, the French “Centre National d’Etudes Spatiales”, the European Space Agency, and the National Aeronautics and Space Administration of the USA. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Forearm vascular resistance responses to the Valsalva maneuver in healthy young and older adults.

Effective end-organ peripheral vascular resistance responses are critical to blood pressure control while upright, and prevention of syncope (fainting). The Valsalva maneuver (VM) induces blood pressure decreases that evoke baroreflex-mediated vasoconstriction. We characterized beat-to-beat forearm vascular resistance (FVR) responses to the VM in healthy adults, evaluated the impact of age and sex on these responses, and investigated their association with orthostatic tolerance (OT; susceptibility to syncope). We hypothesized that individuals with smaller FVR responses would be more susceptible to syncope. Healthy young (N = 36; 19 women; age 25.4 ± 4.6years) and older (N = 21; 12 women; age 62.4 ± 9.6years) adults performed a supine 40mmHg, 20s VM. Graded 60° head-up-tilt with combined lower body negative pressure continued to presyncope was used to determine OT. Non-invasive beat-to-beat blood pressure and heart rate (finger plethysmography) were recorded continuously. FVR was calculated as mean arterial pressure (MAP) divided by brachial blood flow velocity (Doppler ultrasound) relative to baseline. The VM produces a distinctive FVR pattern that peaks (+137.1 ± 11.6%) in phase 2B (17.5 ± 0.3s) as the baroreflex responds to low-pressure perturbations. This response increased with age overall (p < 0.001) and within male (p = 0.030) and female subgroups (p < 0.001). Maximum FVR during the VM was significantly correlated with maximal tilt FVR (r = 0.364; p = 0.0153) and with OT when expressed relative to the MAP decrease in phase 2A (Max FVR (%)/MAP2A-1; r = 0.337; p = 0.0206). This is the first characterization of FVR responses to the VM. The VM elicits large baroreflex-mediated increases in FVR; small FVR responses to the VM may indicate susceptibility to syncope.

Functional evidence of low-pressure cardiopulmonary baroreceptor reinnervation 1year after heart transplantation.

Heart transplantation (HTx) implies denervation of afferent neural connections. Reinnervation of low-pressure cardiopulmonary baroreceptors might impact the development and treatment of hypertension, but little is known of its occurrence. The present prospective study investigated possible afferent reinnervation of low-pressure cardiopulmonary baroreceptors during the first year after heart transplantation. A total of 50 heart transplant recipients (HTxRs) were included and were evaluated 7-12weeks after transplant surgery, with follow-up 6 and 12months later. In addition, a reference group of 50 healthy control subjects was examined once. Continuous, non-invasive recordings of cardiovascular variables were carried out at supine rest, during 15min of 20° head-up tilt, during Valsalva maneuver and during 1min of 30% maximal voluntary handgrip. In addition, routine clinical data including invasive measurements were used in the analyses. During the first year after HTx, the heart rate (HR) response to 20° head-up tilt partly normalized, a negative relationship between resting mean right atrial pressure and HR tilt response developed, low-frequency variability of the RR interval and systolic blood pressure at supine rest increased, and the total peripheral resistance response to Valsalva maneuver became stronger. Functional assessments suggest that afferent reinnervation of low-pressure cardiopulmonary receptors occurs during the first year after heart transplantation, partially restoring reflex-mediated responses to altered cardiac filling.

Difference in cardiovascular response during orthostatic stress in Parkinson's disease and multiple system atrophy.

Although orthostatic hypotension is more prominent in multiple system atrophy (MSA) than in Parkinson's disease (PD), there is no study comparing the degree of decrease in total peripheral resistance and cardiac response during orthostatic stress between both diseases. In this study, we examined whether there is a difference in cardiovascular response between MSA and PD. We examined the results of the head-up tilt test in 68 patients with MSA, 28 patients with cardiac non-denervated PD, and 70 patients with cardiac denervated PD whose total peripheral resistance after 60° tilting was lower than the value at 0°. Differences in cardiac output and blood pressure changes were compared against the decrease in total peripheral resistance. There was no difference in the degree of decrease in total peripheral resistance among the three groups. However, the slope of the regression line revealed that the increase in cardiac output against the change in total peripheral resistance was significantly lower in the MSA group than in the cardiac non-denervated and denervated PD groups, and that the decrease in systolic blood pressure against the change in total peripheral resistance was significantly greater in the MSA group than in the cardiac non-denervated and denervated PD groups. In MSA, the cardiac response during orthostatic stress is lower than that in PD, possibly underlying the fact that orthostatic hypotension is more prominent in MSA than in PD.

Maternal B12, Folate and Homocysteine Concentrations and Offspring Cortisol and Cardiovascular Responses to Stress.

ContextImbalances in maternal 1-carbon nutrients (vitamin B12, folate) have been shown to be associated with higher offspring cardiometabolic risk markers in India.ObjectiveWe examined the hypothesis that low plasma vitamin B12 (B12) and high folate and homocysteine concentrations in the mother are associated with higher hypothalamic–pituitary–adrenal axis (cortisol) and cardiovascular responses during the Trier Social Stress Test for Children (TSST-C) in an Indian birth cohort.MethodsAdolescents (n = 264; mean age: 13.6 years), whose mothers’ plasma B12, folate and total homocysteine concentrations had been measured during pregnancy, completed 5-minutes each of public speaking and mental arithmetic tasks in front of 2 unfamiliar “judges” (TSST-C). Baseline and poststress salivary cortisol concentrations were measured. Heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the TSST-C using a finger cuff; beat-to-beat values were averaged for these periods, respectively. ResultsMaternal low B12 status (plasma B12 < 150 pmol/L) was associated with greater cortisol responses to stress in the offspring (P < .001). Higher homocysteine concentrations were associated with greater offspring heart rate response (P < .001). After adjustment for multiple comparisons, there were nonsignificant associations between higher maternal folate concentrations and offspring total peripheral resistance response (P = .01).ConclusionOur findings suggest that maternal 1-carbon nutritional status may have long-term programming implications for offspring neuroendocrine stress responses.

Sex Differences in the Sympathetic Neural Recruitment and Hemodynamic Response to Head-Up Tilt in Older Hypertensives.

This study tested the hypothesis that older hypertensive women display augmented pressor responses and aberrant sympathetic neural discharge patterning in response to orthostatic stress versus older hypertensive men. We evaluated, in older hypertensive and normotensive men and women (n=12 each group), blood pressure, heart rate, cardiac index (acetylene rebreathing), total peripheral resistance, and muscle sympathetic nerve activity (microneurography) at baseline (supine; 3 minutes) and during graded head-up tilt (30° for 5 minutes and 60° for 20 minutes). Sympathetic action potential discharge patterns were studied using wavelet-based methodology. In the upright posture, systolic and diastolic blood pressure responses were greater in hypertensive women versus hypertensive men and normotensive women (P<0.05). No differences existed in the heart rate, stroke index, or cardiac index response between groups; however, the total peripheral resistance response throughout graded head-up tilt was markedly greater in hypertensive women (P<0.01). Yet, the increase in integrated muscle sympathetic nerve activity burst frequency and burst incidence were similar between hypertensive women and men in the supine and upright postures. However, the increase in the mean action potential content per integrated burst and recruitment of previously dormant, larger-sized action potentials during 60° head-up tilt was greater in hypertensive women versus hypertensive men and normotensive women (P<0.001). Therefore, total sympathetic action potential firing frequency was markedly greater in hypertensive women throughout 60° head-up tilt (P<0.001). In conclusion, older hypertensive women displayed exaggerated pressor and peripheral vasoconstrictor responses to orthostasis versus hypertensive men, under conditions of augmented and aberrant sympathetic neural recruitment, rather than increased burst frequency, in the upright posture.

Autonomic cardiovascular control changes in recent heart transplant recipients lead to physiological limitations in response to orthostatic challenge and isometric exercise

PurposeHeart transplantation causes denervation of the donor heart, but the consequences for cardiovascular homeostasis remain to be fully understood. The present study investigated cardiovascular autonomic control at supine rest, during orthostatic challenge and during isometric exercise in heart transplant recipients (HTxR).MethodsA total of 50 HTxRs were investigated 7–12 weeks after transplant surgery and compared with 50 healthy control subjects. Continuous, noninvasive recordings of cardiovascular variables were carried out at supine rest, during 15 min of 60° head-up tilt and during 1 min of 30% of maximal voluntary handgrip. Plasma and urine catecholamines were assayed, and symptoms were charted.ResultsAt supine rest, heart rate, blood pressures and total peripheral resistance were higher, and stroke volume and end diastolic volume were lower in the HTxR group. During tilt, heart rate, blood pressures and total peripheral resistance increased less, and stroke volume and end diastolic volume decreased less. During handgrip, heart rate and cardiac output increased less, and stroke volume and end diastolic volume decreased less. Orthostatic symptoms were similar across the groups, but the HTxRs complained more of pale and cold hands.ConclusionHTxRs are characterized by elevated blood pressures and total peripheral resistance at supine rest as well as attenuated blood pressures and total peripheral resistance responses during orthostatic challenge, possibly caused by low-pressure cardiopulmonary baroreceptor denervation. In addition, HTxRs show attenuated cardiac output response during isometric exercise due to efferent sympathetic denervation. These physiological limitations might have negative functional consequences.

Dietary nitrate improves muscle microvascular reactivity and lowers blood pressure at rest and during isometric exercise in untreated hypertensives.

This double-blind, cross-over study examined in drug-naïve hypertensives the effects of a single dose of dietary nitrate (beetroot juice, BRJ) on (a) office/ambulatory BP and arterial stiffness, (b) muscle microvascular function, and (c) hemodynamic responses and cardiovagal baroreceptor sensitivity (cBRS) at rest and during isometric exercise. Eighteen untreated hypertensives (44.0±2.6years) consumed randomly, a nitrate-rich (8.1mmol-BRJnitrate ) and a nitrate-depleted (BRJplacebo ) BRJ. Office BP and pulse wave velocity were assessed before/after BRJ. An occlusion-reperfusion maneuver with continuous monitoring of muscle oxygenated hemoglobin (O2 Hb) and total hemoglobin (tHb), via NIRS, followed. Participants performed submaximal isometric handgrip with beat-by-beat monitoring of hemodynamics and cBRS. Ambulatory BP assessment followed. During reperfusion, following arterial occlusion, the magnitude and rate of muscle microvascular reoxygenation (O2 Hb) and red blood cell content (tHb) were higher in BRJnitrate vs BRJplacebo (P<0.05), suggesting improved microvascular reactivity. Office/ambulatory BP were lower following BRJnitrate vs BRJplacebo (P<0.05); pulse-wave-velocity was not altered. During isometric handgrip, BP and peripheral resistance rise were smaller in BRJnitrate vs BRJplacebo (P<0.01-0.05), with no differences in cBRS. In drug-naïve hypertensives, a single dose of BRJ induces (a) short-term reductions in resting/ambulatory BP, (b) acute improvements in muscle microvascular function, and (c) attenuation in BP and peripheral resistance responses during isometric exercise.

Mechanisms of blood pressure control following acute exercise in adolescents: Effects of exercise intensity on haemodynamics and baroreflex sensitivity.

What is the central question of this study? What are the autonomic and vascular components of the baroreflex during hypotension following different exercise intensities in adolescents? What is the main finding and its importance? Hypotension after high-intensity exercise lasted 60min, whereas following moderate-intensity exercise, blood pressure was restored after 20min. Stroke volume and peripheral resistance responses were different between intensities. Post both exercise intensities, baroreflex sensitivity was lowered mainly due to the autonomic component, which returned to baseline 60min post-exercise. The different haemodynamic stimuli indicate potential differences in cardiovascular health benefits of exercise intensity in healthy adolescents. This work aimed to investigate the time course of changes in baroreflex sensitivity (BRS) and its vascular and autonomic components after different exercise intensities in adolescents. Thirteen male adolescents (age 13.9±0.5years) completed on separate days in a counterbalanced order (1) high-intensity interval exercise (HIIE): 8×1min running at 90% of maximal aerobic speed with 75s of active recovery; (2) moderate-intensity interval exercise (MIIE): 10-12 bouts of 1min running at 90% of gas exchange threshold with 75s of active recovery; and (3) resting as a control. Supine heart rate and blood pressure were monitored continuously at baseline, and 5 and 60min following the conditions. A cross-spectral method (low frequency gain; LFgain ) was used to determine BRS gain. Arterial compliance (AC) was assessed as the BRS vascular component. LFgain /AC was used as the autonomic component. LFgain decreased 5min post-exercise bouts (HIIE P<0.001; MIIE P=0.002), but returned to baseline at 60min post-exercise. AC increased at 5min post-exercise for all conditions (P=0.048), and returned to baseline at 60min post-exercise. LFgain /AC decreased 5min post-exercise bouts (HIIE P=0.001; MIIE P=0.004), but returned to baseline values at 60min post-exercise. Mean arterial pressure was lowered by both exercise intensities at 5min post-exercise, but remained decreased at 60min post-exercise following HIIE only. In conclusion, BRS decreases 5min following exercise in adolescents independent of exercise intensity and is mainly driven by a lowered autonomic response. At 60min post-exercise, the ability of BRS to regulate blood pressure is restored after MIIE but not after HIIE, indicating exercise intensity-dependent mechanisms.

Acute Aerobic Exercise Does Not Alter the Pressor Response to the Cold Pressor Test

Circulating vasodilator compounds are elevated after acute aerobic exercise, which contribute to post‐exercise hypotension and orthostatic intolerance. This suggests that the pressor response during sympathoexciation is blunted following acute aerobic exercise. The cold pressor test (CPT) is a sympathoexcitatory maneuver that increases heart rate and blood pressure. However, it is not known if cardiovascular dynamics during 2 minutes of the CPT are altered following acute aerobic treadmill exercise.PurposeTest the hypothesis that cardiovascular responses to the CPT following acute aerobic treadmill exercise are blunted.MethodsTwelve healthy participants (23±4 years, 6 females) completed a CPT before and 10 minutes after treadmill exercise (20 minutes at 65–70% of age predicted maximum heart rate). During the CPT, a hand was submerged up to the wrist in ice water (~0°C) for 120 seconds. Heart rate (ECG) and blood pressure (photoplethysmography) were continuously recorded. Stroke volume was determined using Modelflow. Cardiac output was calculated as the product of heart rate and stroke volume. Total peripheral resistance was determined by dividing mean arterial pressure by cardiac output. Data were analyzed in 30 second increments. Perceived pain (0 = no pain, 10 = most severe pain) was obtained after each CPT. Data during the CPT are presented as a change from baseline and analyzed using repeated measures ANOVA.ResultsBaseline heart rate was higher post exercise (64 ± 8 vs. 86 ± 13 bpm, P &lt; 0.01). Baseline mean arterial pressure (85 ± 10 vs. 80 ± 8 mmHg, P = 0.05) and systolic blood pressure (122 ± 14 vs. 114 ± 12 mmHg, P &lt; 0.01) were lower post exercise. Baseline diastolic blood pressure (63 ± 8 vs. 61 ± 6 mmHg, P = 0.25), stroke volume (99 ± 14 vs. 97 ± 16 mL, P = 0.35), cardiac output (6.2 ± 0.8 vs. 6.6 ± 0.8 L/min, P = 0.16), and total peripheral resistance (13.9 ± 2.8 vs. 12.3 ± 1.8 mmHg/L/min, P = 0.10) were not different between pre‐ and post‐exercise. During the CPT, the increase in heart rate was greater pre‐ vs. post‐exercise at 30 seconds (22 ± 16 vs. 17 ± 13 bpm, P = 0.02) and 60 seconds (18 ± 16 vs. 12 ± 9 bpm, P &lt; 0.01). Pre‐ and post‐exercise mean arterial pressure increased throughout the CPT and peaked at 90 seconds for pre‐ (26 ± 10 bpm, P &lt; 0.01) and post‐exercise (27 ± 9 mmHg, P &lt; 0.01). There were no differences in the mean arterial pressure responses to the CPT between pre‐and post‐exercise (P &gt; 0.99). Pre‐ and post‐exercise total peripheral resistance increased throughout the CPT and peaked at 120 seconds for pre‐ (5.7 ± 4.7 mmHg/L/min, P &lt; 0.01) and post‐exercise (5.0 ± 3.3 mmHg/L/min, P &lt; 0.01). There were no differences in the total peripheral resistance responses during the CPT between pre‐ and post‐exercise (P &gt; 0.13 for all). Perceived pain of the CPT was not different between pre‐ and post‐exercise (5 ± 2 vs. 6 ± 2 a.u., P = 0.13).ConclusionPost‐exercise heart rate responses to the CPT were blunted while mean arterial pressure and total peripheral resistance responses were not different between pre‐ and post‐exercise. These data indicate that the pressor responses to the CPT are not influenced by acute aerobic exercise whereas the heart rate response is attenuated.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abnormal haemodynamic postural response in patients with chronic heart failure.

AimThe objective was to evaluate in treated heart failure (HF) patients whether multidrug therapy interferes with the cardiovascular autonomic response to postural stress.Methods and resultsBlood pressure (BP; Finapres), heart rate (HR), stroke volume, and total peripheral resistance (TPR) responses to standing up were measured in 33 HF patients and 10 healthy age‐matched controls. Ten hypertensive (HT) patients treated with a similar combination of drugs but without heart failure served as reference subjects to account for use of medication. Frequency domain measures of HR and BP variability were calculated as correlates of cardiovascular autonomic function. Postural hypotension was found in 16 out of 33 HF patients independently from New York Heart Association functional class. In HF patients vs. HT patients and healthy controls the haemodynamic postural response was abnormal with a large initial BP fall and a slackened reflex increase in TPR resulting in inadequate BP recovery. HR and BP variability were normal in HT patients and healthy controls but attenuated in HF patients. The magnitude of the postural HR, stroke volume, and TPR responses as well as HR and BP variability was inversely related to the New York Heart Association class.ConclusionsIn HF patients, the autonomic vasomotor response to postural stress is abnormal, more pronounced with increasing disease severity, and frequently associated with overt postural hypotension. These phenomena appear related to the cardiac condition rather than treatment.

Peripheral Vascular Resistance Impairment during Isometric Physical Exercise in Normotensive Offspring of Hypertensive Parents.

BackgroundA family history of hypertension is associated with vascular and autonomic abnormalities, as well as an impaired neurohemodynamic response to exercise.ObjectiveTo test the hypothesis that normotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.MethodsThe study included 37 normotensive volunteers of both sexes who were sedentary, eutrophic, and nonsmokers, comprising 23 with (FH+; 24 ± 3 years) and 14 without (FH-; 27 ± 5 years) a family history of hypertension. Blood pressure, heart rate (DIXTAL®), forearm blood flow (Hokanson®), and peripheral vascular resistance were simultaneously measured for 3 minutes during rest and, subsequently, for 3 minutes during an isometric exercise at 30% of maximal voluntary contraction (Jamar®).ResultsAt rest, the FH+ and FH- groups present similar mean blood pressure (83 ± 7 versus 83 ± 5 mmHg, p = 0.96), heart rate (69 ± 8 bpm versus 66 ± 7 bpm, p = 0.18), forearm blood flow (3 ± 1 mL/min/100 mL versus 2.7 ± 1 mL/min/100 mL, p = 0.16), and peripheral vascular resistance (30 ± 9 units versus 34±9 units, p = 0.21), respectively. Both groups showed a significant and similar increase in mean blood pressure (∆ = 15 ± 7 mmHg versus 14 ± 7 mmHg, p = 0.86), heart rate (∆ = 12 ± 8 bpm versus 13 ± 7 bpm, p = 0.86), and forearm blood flow (∆ = 0.8 ± 1.2 mL/min/100 mL versus 1.4 ± 1.1 mL/min/100 mL, p = 0.25), respectively, during exercise. However, individuals in the FH+ group showed no reduction in peripheral vascular resistance during exercise, which was observed in the FH- group (∆ = -0.4 ± 8.6 units versus -7.2 ± 6.3 units, p = 0.03).ConclusionNormotensive individuals with a family history of hypertension present an impaired peripheral vascular resistance response to exercise.

Accelerometer-determined physical activity and the cardiovascular response to mental stress in children.

Cardiovascular reactivity has been associated with future hypertension and cardiovascular mortality. Higher physical activity (PA) has been associated with lower cardiovascular reactivity in adults, but little data is available in children. The purpose of this study was to examine the relationship between PA and cardiovascular reactivity to mental stress in children. Cross-sectional study. This study sample included children from the Oswego Lead Study (n=79, 46% female, 9-11 years old). Impedance cardiography was performed while children participated in a stress response protocol. Children were also asked to wear Actigraph accelerometers on their wrists for 3 days to measure intensity and duration of PA and sedentary time. In multivariable models, moderate to vigorous (MV) PA was associated with lower body mass index (BMI) percentile and lower total peripheral resistance (TPR) response to stress (beta=-0.025, p=0.02; beta=-0.009, p=0.05). After additional adjustment for BMI, MVPA was also associated with lower diastolic blood pressure response to stress (beta=-0.01, p=0.03). Total PA and sedentary time were not associated with BMI or cardiovascular responses to stress. A modest, inverse relation of PA to vascular reactivity to mental stress was observed in children. These data provide confirmatory evidence that the promotion of PA recommendations for children are important for cardiovascular health.

Maximal expiratory pressure and Valsalva manoeuvre do not produce similar cardiovascular responses in healthy men.

What is the central question of this study? This is the first study to evaluate and describe the cardiovascular responses during maximal expiratory pressure compared with the Valsalva manoeuvre, and whether those responses are similar. What is the main finding and its importance? This study showed that the duration of the manoeuvres appears to be responsible for the different physiological mechanisms involved in the cardiovascular responses to each manoeuvre and that the intensity of expiratory effort was related to the response in maximal expiratory pressure. These results are important to identify the risks to which subjects are exposed when performing these manoeuvres. The main purpose of this study was to compare the cardiovascular responses between the Valsalva manoeuvre (VM) and maximal expiratory pressure (MEP) and to evaluate the effect of age on these responses. Twenty-eight healthy men were evaluated and divided into two groups, younger (n=15, 25±5years) and middle aged (n=13, 50±5years), and they performed the VM and MEP measurement. The VM consisted of an expiratory effort (40mmHg) against a manometer for 15s, and the MEP was performed according to American Thoracic Society guidelines. The cardiovascular responses were analysed at rest, isotime (3s), peak, nadir and recovery, and the cardiovascular variations (Δ) were calculated as peak or isotime minus resting values. For the statistical analysis, we used two-way ANOVA (P<0.05). We observed that MEP and the VM generate similar changes in cardiac output (P>0.05), but MEP presents higher values for mean arterial pressure (MAPPeak , MAPIsotime , ΔMAP and ΔMAPIsotime ) than those observed in the VM (P<0.05). The execution time of the manoeuvres (VM ∼15s and MEP ∼5s) appears to be largely responsible for the activation of different physiological mechanisms involved in the cardiovascular control for each manoeuvre, and the intensity of expiratory effort is related to the higher response of MAP and peripheral vascular resistance (PVRIsotime and ΔPVRIsotime ) during MEP (P<0.05). Moreover, it appears that age affects only the heart rate and PVR responses (P<0.05), which were higher in the young and middle-aged group, respectively. Based on these findings, we can conclude that MEP and the VM do not generate similar cardiovascular responses, except for cardiac output.

Heterogenous haemodynamic effects of adaptive servoventilation therapy in sleeping patients with heart failure and Cheyne-Stokes respiration compared to healthy volunteers.

This study investigated the haemodynamic effects of adaptive servoventilation (ASV) in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) versus healthy controls. Twenty-seven HF patients with CSR and 15 volunteers were ventilated for 1h using a new ASV device (PaceWave™). Haemodynamics were continuously and non-invasively recorded at baseline, during ASV and after ventilation. Prior to the actual study, a small validation study was performed to validate non-invasive measurement of Stroke volume index (SVI). Non-invasive measurement of SVI showed a marginal overall difference of -0.03±0.41 L/min/m(2) compared to the current gold standard (Thermodilution-based measurement). Stroke volume index (SVI) increased during ASV in HF patients (29.7±5 to 30.4±6 to 28.7±5mL/m(2), p<0.05) and decreased slightly in volunteers (50.7±12 to 48.6±11 to 47.9±12mL/m(2)). Simultaneously, 1h of ASV was associated with a trend towards an increase in parasympathetic nervous activity (PNA) in HF patients and a trend towards an increase in sympathetic nervous activity (SNA) in healthy volunteers. Blood pressure (BP) and total peripheral resistance response increased significantly in both groups, despite marked inter-individual variation. Effects were independent of vigilance. Predictors of increased SVI during ASV in HF patients included preserved right ventricular function, normal resting BP, non-ischaemic HF aetiology, mitral regurgitation and increased left ventricular filling pressures. This study confirms favourable haemodynamic effects of ASV in HF patients with CSR presenting with mitral regurgitation and/or increased left ventricular filling pressures, but also identified a number of new predictors. This might be mediated by a shift towards more parasympathetic nervous activity in those patients.

Vascular Mechanisms of Post-exercise Blood Pressure Responses in Peripheral Artery Disease.

This study aimed to analyze the vascular mechanisms involved in post-resistance decreases in blood pressure in patients with peripheral artery disease. 17 patients underwent 2 experimental sessions conducted in random order: resistance exercise (REx-3×10 reps in 8 exercises with intensity of ~ 60% of 1 RM) and control (C- resting on the exercise machines for 50 min). Before and after each experimental session, blood pressure, reflected wave indicators, pulse wave velocity, blood flow, blood flow post-reactive hyperemia and peripheral vascular resistance responses were obtained. Both sessions increased brachial systolic, diastolic and mean blood pressure (greatest increase REx: 11 mmHg; greatest increase C: 19 mmHg; P<0.01); however, the increases were greater after the C session (P<0.01). Reflected wave indicators increased only after the C session (P<0.06), while pulse wave velocity increased similarly after both sessions (P=0.66). Individual analyses indicated a large variability between patients in vascular variables responses. A single bout of REx decreased blood pressure in peripheral artery disease patients, and these responses were followed by changes in reflected wave indicators. The other factors presented high individual variability, and thus it was not possible to identify specific factors associated with blood pressure reduction in peripheral artery disease patients.

Hemodynamic responses to angiotensin-(1-7) in women in their third trimester of pregnancy

Background: To understand the role of Angiotensin-(1-7) (Ang-(1-7)) in vasculature of pregnant women, we compared cardiac output (CO), total peripheral resistance (TPR) and forearm blood flow (FBF) responses to Ang-(1-7) infusion between normotensive pregnant women in their third trimester and healthy age matched non-pregnant women. The responses of skin microcirculation to Ang-(1-7) were tested in preeclamptic, normotensive pregnant and non-pregnant women. Responses to Angiotensin II (Ang II) were also determined. Methods: Non-invasive methods for systemic (bioimpedance and VascuMAP), FBF (venous occlusion strain gauge plethysmography), and skin (laser Doppler) hemodynamics assessments were used. Results: Compared to non-pregnant women, systemic infusion of Ang-(1-7) (2000 pmol/min) resulted in a greater increase in CO (9.4 ± 6.4 versus −3.3 ± 2.1%, n = 9–10) in normotensive pregnant women. Brachial local infusion of Ang-(1-7) had no effect on FBF in either group. In non-pregnant and normotensive pregnant women, local Ang II induced a dose-dependent decrease in FBF and increase in forearm resistance at 50 and 100 pmol/min (p < 0.05 versus corresponding baseline, n = 7–10). Following iontophoretic application of 5 mmol/l dose of Ang-(1-7), the change in skin flow was higher in normotensive pregnant versus preeclamptic women (182.5 ± 93 versus 15.76 ± 19.46%, n = 14–15). Skin flow was lower in normotensive pregnant versus preeclamptic women (−46.5 ± 48.7 versus 108.7 ± 49.1%, n = 14–15) following Ang II infusion at 1.0 pmol/min. Conclusion: In the third trimester of pregnancy, Ang-(1-7) induces alterations in CO and differentially regulates micro- and macro-circulations, depending on the dose. Dysregulation in skin vasculature may contribute to the development of vascular dysfunction and hypertension in preeclampsia.

The Impact of Emotion-Related Autonomic Nervous System Responsiveness on Pain Sensitivity in Female Patients With Fibromyalgia

Patients with fibromyalgia have shown hyporeactive autonomic nervous system (ANS) responses to physical stressors, augmented pain to ANS changes, and heightened negative emotions, which can increase pain. This study examined ANS reactivity to negative emotions and its association with pain in fibromyalgia and control participants. Sixty-two women with fibromyalgia and 59 women in a control group recalled neutral, and anger- and sadness-eliciting experiences while ANS activity was monitored. Clinical and experimental pain were assessed in response to each emotion. Compared with neutral recall, heart rate (p = .050), mean arterial pressure (p < .001), and high-frequency heart rate variability (p = .012) increased in response to sadness, whereas heart rate decreased (p = .002) and mean arterial pressure increased (p < .001) in response to anger; however, ANS responses did not differ between patients and control participants (all p > .29). Among patients only, decreased preejection period (anger-pain threshold: r = 0.31, p = .018) and total peripheral resistance in response to negative emotions (anger-pain tolerance: r = 0.35, p = .025; sadness-pain threshold: r = 0.51, p < .001; sadness-pain tolerance: r = 0.61, p < .001) correlated with more pain. These data suggest that the ANS is not hyporesponsive to elicited emotions in fibromyalgia; however, patients with a larger pain response showed an ANS response pattern reflecting heightened β-adrenergic and reduced α-adrenergic reactivity. Future research should test whether a specific ANS response pattern to emotions is a consequence of increased pain or whether it amplifies pain.

Autonomic effects of suggestive placebo interventions to increase or decrease blood pressure: A randomized controlled trial in healthy subjects

ObjectivePlacebo effects on pain and other subjective parameters are well-established, but the evidence for placebo effects on autonomic functions is scarce. Our randomized-controlled trial aimed to investigate autonomic responses after a suggestive placebo intervention intended to increase or decrease blood pressure (BP). Methods92 healthy subjects inhaled a placebo spray with the prior suggestion that it contained an effective drug to either increase or decrease BP, or the information that a placebo was administered (controls). BP, heart rate, stroke volume, peripheral resistance, heart rate variability and skin conductance level were monitored 30min before and after placebo administration. The expected and the subjectively perceived drug effect were measured by means of visual analog scales. ResultsWe found no statistically significant differences between the groups with respect to BP, heart rate, stroke volume, total peripheral resistance and heart rate variability responses to the verbal suggestions. Skin conductance response was more pronounced in the BP decrease group compared with controls (p=0.04), but this finding might be due to chance, given the multiple tests. Within the total study sample, BP, total peripheral resistance, low frequency power of heart rate variability and skin conductance were significantly higher after the placebo spray independent of the associated suggestions. Subjects in the BP increase and BP decrease condition had higher ratings of the expected and the subjectively perceived drug effect compared with controls (all p<0.05). ConclusionWe found no evidence that specific verbal suggestions during placebo interventions affect BP in healthy subjects.

Individual Differences in Cardiac and Vascular Components of the Pressor Responses to Isometric Handgrip Exercise in Humans

The aim of this study was to test the hypotheses that, in humans, cardiac output (CO) and total peripheral vascular resistance (TPR) responses to isometric exercise vary among individuals, and that the individual differences are related to the muscle metaboreflex and the arterial baroreflex functions. Healthy subjects (n = 32) performed 1‐min isometric handgrip exercise (HG) at 50% of maximal voluntary contraction, followed by a 4‐min period of post‐exercise muscle ischemia (PEMI) to selectively maintain activation of the muscle metaboreflex. In 11 subjects the pressor response to HG occurred solely by the increase in CO, but in 18 subjects it occurred due to both the increases in CO and TPR, and further it occurred solely via the increase in TPR in 3 subjects. Thus the pressor components varied widely among subjects. The CO and TPR responses during HG were positively correlated with those responses during PEMI, respectively. In addition, the CO response to PEMI was negatively correlated with the PEMI‐induced changes in an index of cardiac vagal tone and cardiac baroreflex sensitivity. We conclude that CO and TPR responses to HG vary among individuals, and that the individual differences in components of the pressor response could be attributed in part to the variations in the muscle metaboreflex and the arterial baroreflex functions. This study was supported by the grants from Japan Society for the Promotion of Science.