Mild Lower Body Negative Pressure Research Articles

Cardiovascular Responses to Mild Lower Body Negative Pressure during Spaceflight

IntroductionWeightlessness during spaceflight causes a chronic cephalad fluid shift that has been hypothesized to underlie numerous risks associated with spaceflight, including the development of ocular structural and functional changes and in rare cases venous thrombosis. Acute use of 25 mmHg lower body negative pressure (LBNP) during spaceflight can partially reverse this headward fluid shift and thus, may represent a promising countermeasure. However, there are limited data on how the cardiovascular system responds to sustained use of mild LBNP during spaceflight when cardiovascular deconditioning and adaptation may cause crewmembers to be more susceptible to orthostatic stressors than they would have been on Earth.PurposeThe purpose of this study was to quantify the heart rate (HR) and blood pressure response throughout ~60 minutes of exposure to 25 mmHg LBNP during spaceflight and determine if this response was augmented at later time points during 6‐month spaceflight missions.HypothesisWe hypothesized that crewmembers would experience an increase in HR during LBNP that would be sufficient to maintain mean arterial pressure (MAP) and this would not be augmented later in spaceflight.MethodsBrachial arterial pressure and HR were measured before and throughout ~60 min of 25 mmHg LBNP after ~45 days (FD45) and ~150 days (FD150) of spaceflight in 12 crewmembers. Total LBNP session times varied slightly due to logistical constraints. MAP and HR changes from baseline with LBNP exposure were analyzed with splines models. Marginal means were used for estimation and statistical comparisons across time and between flight days.ResultsBefore LBNP use, HR was 59 beats per min (BPM 95% CI: 56 – 62) and MAP was 93 mmHg (95% CI: 90 – 96). During LBNP exposure on FD45, HR increased by 9 BPM (95% CI: +7 – +10) at 15 min of exposure, and increased further to +10 BPM (95% CI: +8 – +12) at 30 min, and +11 BPM (95% CI: +9 – +14) at 45 min. On FD150, HR increased by 8 BPM (95% CI: +5 – +11) at 15 min of exposure but plateaued thereafter. MAP decreased by 5 mmHg (95% CI: ‐8 – ‐2) at 15 min and remained lower thereafter. MAP responses during ~60 min of LBNP exposure were not statistically different between FD45 and FD150. A total of 46 sessions of LBNP were successfully completed, and only a single case of mild hypotensive symptoms was reported, and this session was completed.ConclusionThese data suggest that the cardiovascular system can accommodate up to 60 min of sustained use of mild levels of LBNP during long‐duration spaceflight. There was a single report of mild hypotensive symptoms during use of LBNP by an individual who had low blood pressure prior to the start of the LBNP session. Thus, the absolute arterial blood pressure should be taken into consideration when determining if an LBNP session will be a potential challenge to the cardiovascular system during spaceflight.

Effects of Mild Orthostatic Stimulation on Cerebral Pulsatile Hemodynamics.

The augmented cerebral hemodynamic pulsatility could lead to the elevated risk of cerebrovascular disease. To determine the impact of an acute orthostatic challenge on a pulsatile component of cerebral hemodynamics, mild lower body negative pressure (LBNP, -30 mmHg) was applied to 29 men. Middle cerebral artery blood flow velocity (MCAv) was measured by transcranial Doppler technique. Stroke volume (SV) was estimated by the Modelflow method with adjustment by the Doppler ultrasound-measured SV at rest. SV, peak and pulsatile MCAv, and pulsatility index were significantly lower during the LBNP stimulation than those at the baseline (e.g., supine resting) (P < 0.05 for all), whereas mean arterial pressure and mean MCAv remained unchanged. The change in SV with the LBNP stimulation significantly correlated with corresponding changes in peak and pulsatile MCAv (r = 0.617, P < 0.001; r = 0.413, P = 0.026, respectively). These results suggest that pulsatile components of cerebrovascular hemodynamics are dampened during the transient period of orthostatic challenge (as simulated using LBNP) when compared to supine rest, and which is partly due to the modified SV.

UBC-Nepal Expedition: acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea level and high altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g., shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that 1) at rest, SNA would be elevated and FMD would be reduced at HA compared with sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344 m) and HA (5,050 m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n = 5). Our findings were 1) at rest, SNA was elevated (P < 0.01), and absolute FMD was reduced (P = 0.024), but relative FMD remained unaltered (P = 0.061), at HA compared with SL; and 2) despite significantly altering SNA with LBNP (+60.3 ± 25.5%) and LBPP (-37.2 ± 12.7%) (P < 0.01), FMD was unaltered at SL (P = 0.448) and HA (P = 0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA.NEW & NOTEWORTHY The role of the sympathetic nervous system on endothelial function remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic nervous activity at sea level and high altitude and measured brachial endothelial function via flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no effect on endothelial function.

Impact of mild orthostatic stress on aortic-cerebral hemodynamic transmission: insight from the frequency domain.

High cerebral pressure and flow fluctuations could be a risk for future cerebrovascular disease. This study aims to determine whether acute systemic vasoconstriction affects the dynamic pulsatile hemodynamic transmission from the aorta to the brain. We applied a stepwise lower body negative pressure (LBNP) (-10, -20, and -30 mmHg) in 15 young men to induce systemic vasoconstriction. To elucidate the dynamic relationship between the changes in aortic pressure (AoP; estimated from the radial arterial pressure waveforms) and the cerebral blood flow velocity (CBFV) at the middle cerebral artery (via a transcranial Doppler), frequency-domain analysis characterized the beat-to-beat slow oscillation (0.02-0.30 Hz) and the intra-beat rapid change (0.78-9.69 Hz). The systemic vascular resistance gradually and significantly increased throughout the LBNP protocol. In the low-frequency range (LF: 0.07-0.20 Hz) of a slow oscillation, the normalized transfer function gain of the steady-state component (between mean AoP and mean CBFV) remained unchanged, whereas that of the pulsatile component (between pulsatile AoP and pulsatile CBFV) was significantly augmented during -20 and -30 mmHg of LBNP (+28.8% and +32.4% vs. baseline). Furthermore, the relative change in the normalized transfer function gain of the pulsatile component at the LF range correlated with the corresponding change in systemic vascular resistance (r = 0.41, P = 0.005). Regarding the intra-beat analysis, the normalized transfer function gain from AoP to CBFV was not significantly affected by the LBNP stimulation (P = 0.77). Our findings suggest that systemic vasoconstriction deteriorates the dampening effect on the pulsatile hemodynamics toward the brain, particularly in slow oscillations (e.g., 0.07-0.20 Hz).NEW & NOTEWORTHY We characterized the pulsatile hemodynamic transmission from the heart to the brain by frequency-domain analysis. The low-frequency transmission was augmented with a mild LBNP stimulation partly due to the elevated systemic vascular resistance. A systemic vasoconstriction deteriorates the dampening effect on slow oscillations of pulsatile hemodynamics toward the brain.

Cardiothoracic impedance does not reflect beat‐to‐beat changes in cardiac stroke volume during mild lower body negative pressure (707.1)

Background: Variability in cardiac stroke volume (SVV) has been proposed as a clinical tool to assess the magnitude of acute hemorrhage. We investigated how three non‐invasive methods represent the beat‐to‐beat changes of cardiac stroke volume (SV).Methods: Ten healthy subjects underwent mild simulated hemorrhage through lower body negative pressure (LBNP) at ‐30 mmHg after a five minutes resting period at baseline. SV beat‐to‐beat was estimated simultaneously by three non‐invasive methods: Ultrasound Doppler (SV_usd), finger arterial blood pressure curve (SV_bpc) and cardiothoracic impedance (SV_imp). SVV was calculated at respiratory frequency between 0.15 and 0.40 Hz from spectral analysis. The median and 95% confidence intervals (CI) were calculated by Hodges‐Lehman’s estimates from epochs of 120 seconds at baseline and at ‐30 mmHg of LBNP. Statistical differences were calculated by Wilcoxon matched‐pairs signed rank test.Results: SVV_usd and SVV_bpc decreased at ‐30 mmHg LBNP to 32% (18%, 47%) and 32% (21%, 43%) of baseline variability. In contrast, SVV_imp was unchanged at ‐30 mmHg (88% (42%, 182%), p=0.82) relative to baseline.Conclusion: Cardiac stroke volume estimated by Ultrasound Doppler and finger arterial blood pressure curve reflect the same variations beat‐to‐beat during simulated hemorrhage. Cardiothoracic impedance does not reflect beat‐to‐beat changes in SV.Grant Funding Source: The Research Council of Norway

Short-term variability of blood pressure: effects of lower-body negative pressure and long-duration bed rest

Mild lower-body negative pressure (LBNP) has been utilized to selectively unload cardiopulmonary baroreceptors, but there is evidence that arterial baroreceptors can be transiently unloaded after the onset of mild LBNP. In this paper, a black box mathematical model for the prediction of diastolic blood pressure (DBP) variability from multiple inputs (systolic blood pressure, R-R interval duration, and central venous pressure) was applied to interpret the dynamics of blood pressure maintenance under the challenge of LBNP and in long-duration, head-down bed rest (HDBR). Hemodynamic recordings from seven participants in the WISE (Women's International Space Simulation for Exploration) Study collected during an experiment of incremental LBNP (-10 mmHg, -20 mmHg, -30 mmHg) were analyzed before and on day 50 of a 60-day-long HDBR campaign. Autoregressive spectral analysis focused on low-frequency (LF, ~0.1 Hz) oscillations of DBP, which are related to fluctuations in vascular resistance due to sympathetic and baroreflex regulation of vasomotor tone. The arterial baroreflex-related component explained 49 ± 13% of LF variability of DBP in spontaneous conditions, and 89 ± 9% (P < 0.05) on day 50 of HDBR, while the cardiopulmonary baroreflex component explained 17 ± 9% and 12 ± 4%, respectively. The arterial baroreflex-related variability was significantly increased in bed rest also for LBNP equal to -20 and -30 mmHg. The proposed technique provided a model interpretation of the proportional effect of arterial baroreflex vs. cardiopulmonary baroreflex-mediated components of blood pressure control and showed that arterial baroreflex was the main player in the mediation of DBP variability. Data during bed rest suggested that cardiopulmonary baroreflex-related effects are blunted and that blood pressure maintenance in the presence of an orthostatic stimulus relies mostly on arterial control.

Evidence for unloading arterial baroreceptors during low levels of lower body negative pressure in humans

Low levels (i.e., </=20 mmHg) of lower body negative pressure (LBNP) have been utilized to unload "selectively" cardiopulmonary baroreceptors in humans, since steady-state mean arterial pressure and heart rate (HR) have been found unchanged at such levels. However, transient reductions in blood pressure (BP), followed by reflex compensation, may occur without detection, which could unload arterial baroreceptors. The purposes of this study were to test the hypothesis that the arterial baroreflex is engaged even during low levels of LBNP and to determine the time course of changes in hemodynamics. Fourteen healthy individuals (age range 20-54 yr) were studied. BP (Portapres and Suntech), HR (ECG), pulmonary capillary wedge pressure (PCWP) or pulmonary artery diastolic pressure (PDP) and right atrial pressure (RAP) (Swan-Ganz catheter) and hemodynamics (Modelflow) were recorded continuously at baseline and -15- and -30-mmHg LBNP for 6 min each. Application of -15-mmHg LBNP resulted in rapid and sustained falls in RAP and PCWP or PDP, progressive decreases in cardiac output and stroke volume, followed subsequently by transient reductions in both systolic and diastolic BP, which were then restored through the arterial baroreflex feedback mechanism after approximately 15 heartbeats. Additional studies were performed in five subjects using even lower levels of LBNP, and this transient reduction in BP was observed in three at -5- and in all at -10-mmHg LBNP. The delay for left ventricular stroke volume to fall at -15-mmHg LBNP was about 10 cardiac cycles. An increase in systemic vascular resistance was detectable after 20 heartbeats during -15-mmHg LBNP. Steady-state BP and HR remained unchanged during mild LBNP. However, BP decreased, while HR increased, at -30-mmHg LBNP. These results suggest that arterial baroreceptors are consistently unloaded during low levels (i.e., -10 and -15 mmHg) of LBNP in humans. Thus "selective" unloading of cardiopulmonary baroreceptors cannot be presumed to occur during these levels of mild LBNP.

Vasomotor responses to decreased venous return: effects of cardiac deafferentation in humans

We compared haemodynamic and peripheral vasomotor responses to lower body negative pressure (LBNP) in cardiac transplant recipients who had undergone bicaval anastomoses, involving right atrial deafferentation (-RA), and the conventional procedure in which some atrial baroreceptor afferents remain intact (+RA). We measured mean forearm blood flow (FBF) responses using Doppler/ultrasound during three randomised trials involving 0 (baseline), -20 and -40 mmHg LBNP in 15 transplant recipients (9 -RA, 6 +RA) and in eight healthy matched controls. A significant effect of LBNP on FBF existed between control and transplant groups (P < 0.05; two-way ANOVA). Mild LBNP (-20 mmHg), significantly decreased FBF by 29.7 +/- 10.0% relative to baseline in +RA subjects (P < 0.05), whereas the 17.7 +/- 10.3% decrease in -RA subjects was not significant. In response to -40 mmHg LBNP, FBF significantly decreased in control (42.4 +/- 4.6%, P < 0.05) and +RA subjects (33.3 +/- 11.4%, P < 0.05) with no significant change in the -RA group. The response of systolic blood pressure (SBP) to -40 mmHg significantly differed between groups (P < 0.05): -RA subjects decreased significantly (P < 0.05) whilst the decrease in SBP in +RA subjects did not achieve significance and control subjects exhibited an increase. The heart rate increase from baseline to -40 mmHg was significantly attenuated in -RA relative to controls and the +RA group (P < 0.05). The present study demonstrates that atrial deafferentation impairs reflex vasomotor control of the circulation in response to low- and high-level LBNP, indicating that atrial deafferentation may contribute to abnormal arterial pressure regulation.

Age-related changes in vasomotor reflex control of calf venous capacitance response to lower body negative pressure in humans.

The present study was performed to test the hypothesis that calf venous capacitance would be reduced by mild gravitational stress through a vasomotor reflex in humans, and this response could be diminished with advancing age. Nine young (31 +/- 1 years, mean +/- SE) and 9 elderly (69 +/- 1 years) healthy males were exposed to a lower body negative pressure (LBNP) of 15 mmHg. Venous occlusion plethysmography was used to measure calf venous capacitance and calf blood flow. Muscle sympathetic nerve activity (MSNA) was recorded microneurographically from the tibial nerve along with cardiovascular variables. It was found that baseline MSNA was higher [21 +/- 4 (mean +/- SE) vs. 37 +/- 5 bursts x min(-1), young vs. elderly; p < 0.05] and calf venous capacitance was lower (1.71 +/- 0.12 vs. 1.44 +/- 0.10, ml x 100 ml(-1), young vs. elderly; p < 0.05) in the elderly group. At 15 mmHg-LBNP, heart rate and mean arterial pressure both remained unchanged, MSNA was enhanced, and calf blood flow was reduced in all subjects. Calf venous capacitance during LBNP decreased in the young, but did not change in the elderly. A significant negative correlation between percent changes in MSNA and percent changes in calf venous capacitance existed in the young group (y = 20.171x-11.863, r = 20.682; p = 0.0432), but disappeared in the elderly group. The ratio of percent changes in calf venous capacitance to percent changes in MSNA was markedly lower in the elderly (p < 0.01). In conclusion, these results substantiate our hypothesis that calf venous capacitance is reduced by mild LBNP through the vasomotor reflex, and this response is diminished in the elderly.

Beat-to-beat cardiovascular responses to rapid, low-level LBNP in humans.

The hypothesis tested was that there are significant transient changes in the cardiovascular variables after rapid onset and release of mild lower body negative pressure (LBNP, -20 mmHg), even in experimental situations where there is no detectable change in steady-state values. Twelve subjects participated in the study. Heart rate, stroke volume (SV), cardiac output, mean arterial pressure (MAP), total peripheral resistance (TPR), acral and nonacral skin blood flow, and blood flow velocity in the brachial artery were continuously recorded during the pre-LBNP period (0-120 s), during LBNP (120-420 s), and during the post-LBNP period (420-600 s). The main finding was that MAP is transiently but strongly affected by rapid changes in LBNP as small as -20 mmHg. There was also a characteristic asymmetry in cardiovascular responses to the onset and release of LBNP, particularly in the responses in SV. The transient changes in MAP indicate that the neural responses that affect TPR are not fast enough to compensate for the rapid changes in LBNP. In this case, the arterial baroreceptors will be activated as well as the low-pressure baroreceptors that sense central venous pressure. This must be taken into consideration in future discussions of the results of LBNP protocols.

Carotid arterial hemodynamics in response to LBNP in normal subjects: methodological aspects.

Pulsatile changes in blood pressure and arterial diameter were studied noninvasively with applanation tonometry and echo-tracking techniques at the sites of the common carotid artery (CCA) and the carotid arterial bulb (CAB) in 12 healthy volunteers. Determinations were performed before and during application of -10 and -40 mmHg lower body negative pressure (LBNP) to investigate noninvasively the tensile forces acting on the CAB. Together with significantly decreased mean arterial pressure, increased heart rate, forearm vascular resistance, and plasma norepinephrine, the -40 mmHg LBNP stimulus produced the following significant changes in CCA and CAB hemodynamics: 1) for the same decrease in mean arterial pressure, a greater decrease in carotid than in brachial pulse pressure was observed (P < 0.01) due to a significant change in pressure wave transmission and in the timing of the carotid backward pressure wave; and 2) a highly significant decrease in pulsatile changes in diameter and tangential tension occurred, with a greater decrease in systolic than in diastolic tangential tension. Subsequently, cyclic tangential tension decreased more substantially than mean tangential tension. The cyclic changes in tension were quite significant after -40 mmHg LBNP but were already observed for mild -10 mmHg LBNP in which mean systemic blood pressure and heart rate were not modified. During -10 and -40 mmHg LBNP, CCA and CAB compliance and distensibility were unchanged. This study provides evidence that the autonomic nervous system activation produced by the LBNP procedure is associated with significant changes in pressure-wave amplification and in cyclic tensile forces acting on the CAB. These changes, which may occur even for mild LBNP, should be taken into account when interpreting results of the LBNP procedure in humans.

Increase of sympathetic discharge to skeletal muscle but not to skin during mild lower body negative pressure in humans.

1. Haemodynamic studies in humans have concluded that the cutaneous circulation is regulated by cardiopulmonary baroreceptors. In contrast, neurophysiological studies have indicated that skin sympathetic outflow, unlike muscle sympathetic outflow, is unaffected by perturbations in baroreceptor activity. 2. Thus, in an attempt to resolve this discrepancy, both muscle and skin sympathetic nerve activity was recorded during unloading of mainly cardiopulmonary afferents with non-hypotensive lower body negative pressure (LBNP) performed in both normothermic and hyperthermic conditions. The function of the sympathetic activity was studied by estimations of skin blood flow (laser Doppler velocimetry), of calf blood flow (plethysmography) and of sudomotor activity (electrodermal responses). 3. A level of LBNP that caused robust increases in sympathetic outflow and vascular resistance in the skeletal muscle of the lower leg had no effect on sympathetic activity and vascular resistance in the skin of the same region in the same subjects. Both at normothermia and during hyperthermia LBNP decreased electrodermal activity. Experiments performed during sham LBNP and with skin temperature kept constant suggest that the electrodermal response was due to a decrease in skin temperature produced by the LBNP. 4. In conclusion, these findings challenge the concept that the cutaneous circulation participates importantly in the peripheral circulatory adjustments to unloading of cardiopulmonary afferents during orthostatic stress in humans. During non-hypotensive LBNP, the skeletal muscle bed accounts for all of the reflex vasoconstriction in the calf.

Effect of angiotensin II on noradrenaline release in the human forearm.

The aim was to test the hypothesis that in normal humans angiotensin II would stimulate local release of noradrenaline under basal conditions or during a sympathetic stimulus provided by lower body negative pressure (LBNP). Nine healthy volunteers received intra-arterial infusions of angiotensin II, 5 ng.min-1, into the non-dominant forearm. Forearm blood flow (strain gauge plethysmography) and regional noradrenaline spillover (using the tracer methodology of Esler) were measured during angiotensin II alone, LBNP alone, and LBNP plus angiotensin II. Angiotensin II and LBNP decreased forearm blood flow comparably: from 3.1(SD 1.5) to 2.4 (0.9) ml.100 g-1.min-1 during angiotensin II, p < 0.05; and from 3.3(1.5) to 2.5(1.0) ml.100 g-1.min-1 during LBNP, p < 0.05 (p = NS, A-II v LBNP). Angiotensin II had no effect on forearm venous noradrenaline or regional noradrenaline spillover. LBNP increased venous noradrenaline outflow from the forearm, from 1.6(0.40) to 2.1(0.6) nmol.min-1 (p < 0.05), while regional noradrenaline spillover tended to increase, rising from 1.5(0.8) to 2.0(1.0) nmol.100 ml-1.min-1. Angiotensin II did not enhance forearm blood flow or noradrenaline responses to LBNP. In the human forearm, mildly vasoconstrictor infusions of angiotensin II do not increase local release of noradrenaline, either alone or during mild LBNP. At least under these conditions, angiotensin II would not appear to be a potent influence on local sympathetic activity.

Relative contributions of cardiopulmonary and sinoaortic baroreflexes in causing sympathetic activation in the human skeletal muscle circulation during orthostatic stress.

The aim of this study was to reexamine the hypothesis that cardiopulmonary baroreflexes are more important than sinoaortic baroreflexes in causing vasoconstriction in the skeletal muscle circulation during orthostatic stress. We recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve (and forearm blood flow with venous occlusion plethysmography) in normal subjects (innervated ventricles) and in heart transplant recipients (denervated ventricles) during graded lower body negative pressure (LBNP) performed alone and in combination with intravenous infusion of phenylephrine, which was titrated to eliminate the orthostatically induced fall in blood pressure and thus the unloading of both carotid and aortic baroreceptors. The principal new findings are as follows: (1) The increases in both MSNA and forearm vascular resistance during multiple levels of LBNP were not attenuated by heart transplantation, which causes ventricular but not sinoaortic deafferentation. (2) In heart transplant recipients, a small increase in MSNA during mild LBNP was dependent on a decrease in arterial pressure, but in normal subjects, a similar increase in MSNA occurred in the absence of any detectable decrease in the aortic pressure stimulus to the sinoaortic baroreceptors. (3) In normal subjects, the large increase in MSNA during a high level of LBNP was dependent on a decrease in arterial pressure and could be dissociated from the decrease in central venous pressure. Taken together, the findings strongly suggest that sinoaortic baroreflexes are much more important and ventricular baroreflexes are much less important than previously thought in causing reflex sympathetic activation and vasoconstriction in the human skeletal muscle circulation during orthostatic stress.

Paradoxical forearm vasodilatation and haemodynamic improvement during cardiopulmonary baroreceptor unloading in patients with congestive heart failure

1. To examine the contribution of paradoxical reflex forearm vasodilatation during unloading of cardiopulmonary baroreceptors to systemic haemodynamics, the responses of central and peripheral haemodynamics during lower-body negative pressure were measured in 24 patients with chronic congestive heart failure (New York Heart Association functional class II-IV) and were compared with those of 10 normal subjects. 2. Lower-body negative pressure of less than -20 mmHg caused a significant forearm vasoconstriction in normal subjects but not in patients with congestive heart failure. In the individual cases, however, eight patients (subgroup A) had a significant forearm vasoconstriction, whereas 10 patients (subgroup B) had a paradoxical forearm vasodilatation. The remaining six patients had a blunted forearm vascular response. Baseline pulmonary capillary wedge pressure (26 +/- 3 versus 20 +/- 1 mmHg, means +/- SEM) and left ventricular wall stress in end-diastole (57 +/- 6 versus 37 +/- 4 g/cm2) were significantly (P < 0.05) higher in subgroup B than in subgroup A. 3. During lower-body negative pressure of -20 mmHg, the plasma level of noradrenaline, systemic vascular resistance and cardiac index did not change significantly in subgroup A. In subgroup B, however, during this orthostatic stimulus systemic vascular resistance fell significantly from a baseline value of 2023 +/- 109 to 1740 +/- 110 dyn s-1 cm-5 (P < 0.01) and cardiac index increased significantly from a baseline value of 2.0 +/- 0.1 to 2.5 +/- 0.2 1 min-1 m-2 (P < 0.01) despite there being no significant change in the plasma level of noradrenaline. 4. After treatment, a second bout of lower-body negative pressure was applied to seven patients in subgroup B. The forearm vascular response to the second bout of lower-body negative pressure was normalized. 5. These data suggest that the patients with more severe heart failure show a paradoxical forearm vasodilatation during mild lower-body negative pressure and that this altered cardiopulmonary baroreflex control of the circulation serves to improve the depressed cardiac performance.

Carotid arterial haemodynamics after mild degrees of lower-body negative pressure in man

1. Pulsatile changes in the diameter of the common carotid artery were studied transcutaneously using an echo-tracking technique in 15 normal subjects: eight subjects before and during application of graded lower-body negative pressure from -5 to -15 mmHg, and seven subjects before and during weight-bearing head-up tilt at 30 and 60 degrees. 2. In concomitant studies of changes in forearm vascular resistance, it was seen that mild lower-body negative pressure produced deactivation of cardiopulmonary receptors without changes in systemic blood pressure or heart rate. 3. After lower-body negative pressure, a significant decrease in carotid arterial diastolic diameter [from 0.662 +/- 0.028 to 0.624 +/- 0.033 cm (lower-body negative pressure -10 mmHg) and 0.640 +/- 0.030 cm lower-body negative pressure -15 mmHg), P < 0.001 and < 0.05] was observed. 4. After head-up tilt, carotid arterial diameter was also significantly decreased at 30 and 60 degrees, whereas a significant increase in heart rate occurred only at 60 degrees and mean blood pressure did not change. 5. The study provides evidence that the geometry of the arterial wall is substantially modified by non-invasive manoeuvres such as head-up tilting and lower-body negative pressure. The latter is assumed to selectively deactivate human cardiopulmonary receptors, but the present data suggest that local changes may also influence carotid baroreceptors.

Effect of angiotensin converting enzyme inhibition on cardiovascular regulation during reflex sympathetic activation in sodium-replete patients with essential hypertension.

In order to investigate whether angiotensin II (Ang II) may contribute to cardiovascular regulation through facilitation of the adrenergic function, we examined the haemodynamic and humoral effects of the application of lower-body negative pressure (LBNP) in sodium-replete patients with essential hypertension before and after acute and chronic angiotensin converting enzyme (ACE) inhibition. We measured the changes in blood pressure, heart rate, central venous pressure, forearm blood flow, plasma noradrenaline, renin activity and Ang II induced by LBNP of two different magnitudes: a milder one deactivating predominantly the cardiopulmonary receptors (mild LBNP), and a greater one deactivating both the cardiopulmonary and the arterial baroreceptors (strong LBNP). We found that during mild LBNP systemic blood pressure was maintained after acute and chronic ACE inhibition, as in control studies; however, the decrements in forearm blood flow and the increments in forearm vascular resistance caused by LBNP were diminished after ACE inhibition (the latter by 69 and 67%, respectively, in acute and chronic studies), in spite of the fact that the falls in central venous pressure and the increases in noradrenaline (NA) were similar to those observed in control conditions. During strong LBNP, the fall in systemic blood pressure was greater after acute and chronic ACE inhibition than in control conditions and was associated with a reduction in the response of forearm vascular resistance similar to that observed during mild LBNP, while the increments in NA were again superimposable to those seen before ACE inhibition. These alterations in the haemodynamic responses to LBNP induced by ACE inhibition were associated with significant increments in basal plasma renin activity and with marked reductions in Ang II. These findings suggest that even in the sodium-replete state, Ang II exerts a facilitatory action on adrenergic function that is physiologically relevant for the regulation of forearm blood flow and the maintenance of blood pressure during the application of gravitational stresses.

Carotid baroreceptor reflex regulation of forearm vascular resistance in man.

The carotid baroreflex regulation of forearm vascular resistance in man is uncertain. Forearm vascular resistance, blood pressure and R-R interval responses to carotid sinus stimulation were therefore measured in seven healthy men. Carotid stimuli were delivered by gradually applying neck pressure, neck suction or neck suction during simultaneous low-level lower-body negative pressure. Mean arterial blood pressure and R-R interval responses to neck suction and pressure were immediate and were sustained throughout the periods of stimulation. In contrast, forearm vascular responses, were transient. During simultaneous mild lower-body negative pressure (which decreases cardiopulmonary baroreceptor stimulation and increases forearm vascular resistance), neck-suction-induced forearm vasodilation was exaggerated and sustained throughout the entire period of neck suction. There was a linear relationship between the level of resting forearm vascular resistance and the change in resistance produced by carotid stimuli. It is concluded that reflex changes in forearm vascular resistance provoked by carotid baroreceptor stimuli are immediate and evanescent in man. Simultaneous reduction of cardiopulmonary baroreceptor activity heightens the magnitude and duration of forearm vasodilation induced by carotid baroreceptor stimulation.