Higher Levels Of Lower Body Negative Pressure Research Articles

Impact of Increasing Lower Body Negative Pressure and Its Abrupt Release on Left Ventricular Hemodynamics in Anesthetized Pigs.

Lower body negative pressure (LBNP) has been implemented as a tool to simulate systemic effects of hypovolemia, understand orthostatic challenges and study G load stress in humans. However, the exact hemodynamic mechanisms of graded LBNP followed by its abrupt release have not been characterized in detail, limiting its potential applications in humans. Here, we set out to investigate the immediate hemodynamic alterations occurring during LBNP in healthy Landrace pigs. Invasive cardiac monitoring via extensive pressure volume loop analysis was carried out during application of incremental LBNP up to life threatening levels from −15 to −45 mmHg as well as during its abrupt release. Three different sealing positions were evaluated. Incremental LBNP consistently induced a preload dependent depression of systemic hemodynamics according to the Frank-Starling mechanism. Overall, the pressure–volume loop progressively shifted leftwards and downwards with increasing LBNP intensity. The abrupt release of LBNP reverted the above-described hemodynamic changes to baseline values within only three respiratory cycles. These data provide quantitative translational insights into hemodynamic mechanisms of incremental and very high levels of LBNP, levels of seal and effect of abrupt release for future human applications, such as countermeasure development for long spaceflight.

Internal Jugular Vein Volume Pulsatility during Head‐Down Tilt and Lower Body Negative Pressure

The objective of this study was to investigate the impact of internal jugular vein (IJV) distension on blood volume pulsatility. We hypothesized that pulsatility would be enhanced during cephalad fluid shifts and attenuated during caudal fluid shifts. Thirteen young healthy participants (8/5 male/female) were assessed during supine rest (repeated); 3 and 6 degrees of head-down tilt (HDT); and -20, -30, -40 mmHg of lower body negative pressure (LBNP) after at least 5 minutes in each condition. The order of the HDT and LBNP protocols was randomized. Right-side IJV blood volume was estimated using widefield near-infrared spectroscopy and quantified as jugular venous optical attenuation (JVA). Central venous pressure (CVP) was measured using a transducer attached to a catheter inserted into an antecubital vein in the right arm and corrected to the level of the heart. Participants were rightward tilted throughout to facilitate venous pressure measurements. Continuous signals were acquired for 30s in each condition and time-synced at 60Hz. Volume and pressure pulsatility were calculated as the differences between peak and nadir points along the cardiac cycle in JVA and CVP, respectively. Pressure-volume loops were created after ensemble averaging waveforms normalized to the cardiac cycle. Area of the pressure-volume loops and slope of the pressure-volume relationship during atrial filling (i.e., venous drainage) were assessed. Group mean JVA and CVP were highest during 6° HDT and lowest during -40 mmHg LBNP (see figure). Compared to baseline, JVA pulsatility was attenuated during -30 mmHg LBNP (P=0.048) and -40 mmHg LBNP (P=0.004) and was unchanged during each level of HDT (P>0.9). In contrast, CVP pulsatility was attenuated compared to baseline during -20, -30, and -40 mmHg LBNP (P<0.001) and was unchanged during each level of HDT (P>0.68). Area (P=0.088) and slope (P=0.269) of the pressure-volume loop were unchanged across all conditions. In multiple regression analysis, loop area was associated directly with pressure amplitude (P<0.001) but not volume amplitude (P=0.130); model r2=0.69. These data suggest that, while volume pulsatility did decrease when venous distension was reduced by higher levels of LBNP, this was primarily a function of changes in pressure pulsatilty. IJV compliance appeared to be unchanged across a wide range of venous distension. This work has relevance to states where venous pressure and distension are altered, including heart failure and hemorrhagic shock.

Effect of Graded Sympathetic Activation on Regional Cerebral Vascular Conductance

The role of sympathetic nervous system in cerebral blood flow regulation remains poorly characterized. Previous studies have shown heterogeneity in regional cerebral circulation in response to various stimuli such as exercise, hypoxia, hypocapnia, etc. Recently, Ogoh et al. demonstrated that a moderate level (−50 Torr) of lower body negative pressure (LBNP) caused a significant reduction in internal carotid artery (ICA) blood flow, whereas vertebral artery (VA) blood flow remained unchanged, albeit trending towards a lower blood flow. Although a moderate increase in sympathetic nerve activity (SNA) occurs at −50 LBNP, it has been shown that SNA increases progressively with higher levels of LBNP. Whether VA blood flow is protected at higher levels of LBNP remains unknown. In this study, we tested the hypothesis that greater reflex‐mediated sympathetic activation via a higher level of LBNP will reduce conductance and blood flow to both the ICA and VA. In 9 young, healthy men, heart rate (ECG), arterial blood pressure (brachial sphygmomanometer), VA, ICA, and brachial artery blood flow (duplex Doppler ultrasound), middle cerebral artery (MCA) blood velocity (transcranial Doppler) and end‐tidal CO2 (ETCO2; capnograph) were measured at rest, and during 3–5 min of low, moderate and high LBNP (−30, −50, and −70 Torr, respectively). Conductance was calculated as blood flow of the respective artery/mean arterial pressure. Brachial artery blood flow and conductance were significantly reduced during all LBNP trials, indicating reflex‐mediated sympathetic vasoconstriction. Neither ETCO2 (Δ −1.9 ± 1.3 mmHg relative to baseline, p=0.18) nor any of the cerebral blood vessel measures were affected during −30 Torr LBNP. At −50 Torr LBNP, a reduction in ETCO2 (Δ −5.3 ± 1.6 mmHg relative to baseline, p=0.01) was accompanied by a reduction in ICA conductance (Δ −17.0 ± 8.4% baseline, p=0.057) whereas VA conductance remained unchanged (Δ −8.6 ± 5.6% baseline, p=0.24). Interestingly, with a similar reduction in ETCO2 at −70 Torr LBNP (Δ −4.3 ± 1.3 mmHg relative to baseline, p=0.04), there was a significant reduction in both ICA (Δ −13.1 ± 3.1% baseline, p=0.017) and VA conductance (Δ −20.4 ± 5.3% baseline, p=0.019). Thus, VA conductance was unaffected during low and moderate levels of LBNP however, high levels of LBNP induced a significant reduction in VA conductance and blood flow and this reduction appeared to be independent of the decrease in ETCO2. Collectively, these preliminary findings suggest that large increases in reflex‐mediated sympathetic activation via high levels of LBNP causes significant reductions in both ICA and VA conductance and blood flow.Support or Funding Information1 RO1 HL 127071This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope.

Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 ± 5.0 yr) and 15 matched controls (22.8 ± 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P < 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P < 0.01) and the maximal percent increase in total peripheral resistance was reduced (P < 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P < 0.05) and reduced in VVS women at higher levels of LBNP (P < 0.05). Capillary fluid absorption from extra- to intravascular space was reduced by ∼40% in VVS women (P < 0.05). Accordingly, the reduction in cardiac output was more pronounced (P < 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.

Muscle sympathetic nerve activity during intense lower body negative pressure to presyncope in humans

Activation of sympathetic efferent traffic is essential to maintaining adequate arterial pressures during reductions of central blood volume. Sympathetic baroreflex gain may be reduced, and muscle sympathetic firing characteristics altered with head-up tilt just before presyncope in humans. Volume redistributions with lower body negative pressure (LBNP) are similar to those that occur during haemorrhage, but limited data exist describing arterial pressure-muscle sympathetic nerve activity (MSNA) relationships during intense LBNP. Responses similar to those that occur in presyncopal subjects during head-up tilt may signal the beginnings of cardiovascular decompensation associated with haemorrhage. We therefore tested the hypotheses that intense LBNP disrupts MSNA firing characteristics and leads to a dissociation between arterial pressure and sympathetic traffic prior to presyncope. In 17 healthy volunteers (12 males and 5 females), we recorded ECG, finger photoplethysmographic arterial pressure and MSNA. Subjects were exposed to 5 min LBNP stages until the onset of presyncope. The LBNP level eliciting presyncope was denoted as 100% tolerance, and then data were assessed relative to this normalised maximal tolerance by expressing LBNP levels as 80, 60, 40, 20 and 0% (baseline) of maximal tolerance. Data were analysed in both time and frequency domains, and cross-spectral analyses were performed to determine the coherence, transfer function and phase angle between diastolic arterial pressure (DAP) and MSNA. DAP-MSNA coherence increased progressively and significantly up to 80% maximal tolerance. Transfer functions were unchanged, but phase angle shifted from positive to negative with application of LBNP. Sympathetic bursts fused in 10 subjects during high levels of LBNP (burst fusing may reflect modulation of central mechanisms, an artefact arising from our use of a 0.1 s time constant for integrating filtered nerve activity, or a combination of both). On average, arterial pressures and MSNA decreased significantly the final 20 s before presyncope (n = 17), but of this group, MSNA increased in seven subjects. No linear relationship was observed between the magnitude of DAP and MSNA changes before presyncope (r = 0.12). We report three primary findings: (1) progressive LBNP (and presumed progressive arterial baroreceptor unloading) increases cross-spectral coherence between arterial pressure and MSNA, but sympathetic baroreflex control is reduced before presyncope; (2) withdrawal of MSNA is not a prerequisite for presyncope despite significant decreases of arterial pressure; and (3) reductions of venous return, probably induced by intense LBNP, disrupt MSNA firing characteristics that manifest as fused integrated bursts before the onset of presyncope. Although fusing of integrated sympathetic bursts may reflect a true physiological compensation to severe reductions of venous return, duplication of this finding utilizing shorter time constants for integration of the nerve signal is required.

Does local heating-induced nitric oxide production attenuate vasoconstrictor responsiveness to lower body negative pressure in human skin?

We tested the hypothesis that local heating-induced nitric oxide (NO) production attenuates cutaneous vasoconstrictor responsiveness. Eleven subjects (6 men, 5 women) had four microdialysis membranes placed in forearm skin. Two membranes were perfused with 10 mM of N(G)-nitro-L-arginine (L-NAME) and two with Ringer solution (control), and all sites were locally heated to 34 degrees C. Subjects then underwent 5 min of 60-mmHg lower body negative pressure (LBNP). Two sites (a control and an L-NAME site) were then heated to 39 degrees C, while the other two sites were heated to 42 degrees C. At the L-NAME sites, skin blood flow was elevated using 0.75-2 mg/ml of adenosine in the perfusate solution (Adn + L-NAME) to a similar level relative to control sites. Subjects then underwent another 5 min of 60-mmHg LBNP. At 34 degrees C, cutaneous vascular conductance (CVC) decreased (Delta) similarly at both control and L-NAME sites during LBNP (Delta7.9 +/- 3.0 and Delta3.4 +/- 0.8% maximum, respectively; P > 0.05). The reduction in CVC to LBNP was also similar between control and Adn + L-NAME sites at 39 degrees C (control Delta11.4 +/- 2.5 vs. Adn + L-NAME Delta7.9 +/- 2.0% maximum; P > 0.05) and 42 degrees C (control Delta1.9 +/- 2.7 vs. Adn + L-NAME Delta 4.2 +/- 2.7% maximum; P > 0.05). However, the decrease in CVC at 42 degrees C, regardless of site, was smaller than at 39 degrees C (P < 0.05). These results do not support the hypothesis that local heating-induced NO production attenuates cutaneous vasoconstrictor responsiveness during high levels of LBNP. However, elevated local temperature, per se, attenuates cutaneous vasoconstrictor responsiveness to LBNP, presumably through non-nitric oxide mechanisms.

Effect of skin surface cooling on central venous pressure during orthostatic challenge

Orthostatic stress leads to a reduction in central venous pressure (CVP), which is an index of cardiac preload. Skin surface cooling has been shown to improve orthostatic tolerance, although the mechanism resulting in this outcome is unclear. One possible mechanism may be that skin surface cooling attenuates the drop in CVP during an orthostatic challenge, thereby preserving cardiac filling. To test this hypothesis, CVP, arterial blood pressure, heart rate, and skin blood flow, as well as skin and sublingual temperatures, were recorded in nine healthy subjects during lower body negative pressure (LBNP) in both normothermic and skin surface cooling conditions. Cardiac output was also measured via acetylene rebreathing. Progressive LBNP was applied at -10, -15, -20, and -40 mmHg at 5 min/stage. Before LBNP, skin surface cooling lowered mean skin temperature, increased CVP, and increased mean arterial blood pressure (all P < 0.001) but did not change mean heart rate (P = 0.38). Compared with normothermic conditions, arterial blood pressure remained elevated throughout progressive LBNP. Although progressive LBNP decreased CVP under both thermal conditions, during cooling CVP at each stage of LBNP was significantly greater relative to normothermia. Moreover, at higher levels of LBNP with skin cooling, stroke volume was significantly greater relative to normothermic conditions. These data indicate that skin surface cooling induced an upward shift in CVP throughout LBNP, which may be a key factor for preserving preload, stroke volume, and blood pressure and improving orthostatic tolerance.

Angiotensin II receptor blockade prevents acute renal sodium retention induced by low levels of orthostatic stress

Depending on its magnitude, lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal, renal tubular, and renal hemodynamic responses, thereby mimicking the renal responses observed in clinical conditions characterized by a low effective arterial volume such as congestive heart failure. Our objective was to evaluate the impact of angiotensin II receptor blockade with candesartan on the renal hemodynamic and urinary excretory responses to a progressive orthostatic stress in normal subjects. Twenty healthy men were submitted to three levels of LBNP (0, -10, and -20 mbar or 0, -7.5, and -15 mm Hg) for 1 hour according to a crossover design with a minimum of 2 days between each level of LBNP. Ten subjects were randomly allocated to receive a placebo and ten others were treated with candesartan 16 mg orally for 10 days before and during the three levels of LBNP. Systemic and renal hemodynamics, renal sodium excretions, and the hormonal response were measured hourly before, during, and for 2 hours after LBNP. During placebo, LBNP induced no change in systemic and renal hemodynamics, but sodium excretion decreased dose dependently with higher levels of LBNP. At -20 mbar, cumulative 3-hour sodium balance was negative at -2.3 +/- 2.3 mmol (mean +/- SEM). With candesartan, mean blood pressure decreased (76 +/- 1 mm Hg vs. 83 +/- 3 mm Hg, candesartan vs. placebo, P < 0.05) and renal plasma flow increased (858 +/- 52 mL/min vs. 639 +/- 36 mL/min, candesartan vs. placebo, P < 0.05). Glomerular filtration rate (GFR) was not significantly higher with candesartan (127 +/- 7 mL/min in placebo vs. 144 +/- 12 mL/min in candesartan). No significant decrease in sodium and water excretion was found during LBNP in candesartan-treated subjects. At -20 mbar, the 3-hour cumulative sodium excretion was + 4.6 +/- 1.4 mmol in the candesartan group (P= 0.02 vs. placebo). Selective blockade of angiotensin II type 1 (AT1) receptors with candesartan increases renal blood flow and prevents the antinatriuresis during sustained lower body negative pressure despite a modest decrease in blood pressure. These results thus provide interesting insights into potential benefits of AT1 receptor blockade in sodium-retaining states such as congestive heart failure.

Hemodynamics of orthostatic intolerance: implications for gender differences.

Women have a greater incidence of orthostatic intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced responsiveness of vascular resistance during orthostatic stress. We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP), stroke volume (SV), and stroke index (SI) during lower body negative pressure (LBNP) and saline infusion in 10 healthy young women and 13 men. Orthostatic tolerance was determined by progressive LBNP to presyncope. LBNP tolerance was significantly lower in women than in men (626.8 +/- 55.0 vs. 927.7 +/- 53.0 mmHg x min, P < 0.01). Women had steeper maximal slopes of Starling curves than men whether expressed as SV (12.5 +/- 2.0 vs. 7.1 +/- 1.5 ml/mmHg, P < 0.05) or normalized as SI (6.31 +/- 0.8 vs. 4.29 +/- 0.6 ml.m-2.mmHg-1, P < 0.05). During progressive LBNP, PCWP dropped quickly at low levels, and reached a plateau at high levels of LBNP near presyncope in all subjects. SV was 35% and SI was 29% lower in women at presyncope (both P < 0.05). Coincident with the smaller SV, women had higher heart rates but similar mean arterial pressures compared with men at presyncope. Vascular resistance and plasma norepinephrine concentration were similar between genders. We conclude that lower orthostatic tolerance in women is associated with decreased cardiac filling rather than reduced responsiveness of vascular resistance during orthostatic challenges. Thus cardiac mechanics and Frank-Starling relationship may be important mechanisms underlying the gender difference in orthostatic tolerance.

GENDER DIFFERENCE IN HEMODYNAMICS OF ORTHOSTATIC INTOLERANCE

PURPOSE To test the hypothesis that a greater incidence of orthostatic intolerance in young women compared with men is related to hemodynamics rather than to a reduced vascular responsiveness during orthostatic stress. METHODS We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP) and stroke volume (SV) during lower body negative pressure (LBNP) and rapid saline infusion in 10 healthy, sedentary women (29.6 ± 1.9 yrs, mean ± SE) and 13 control men (25.5 ± 1.4 yrs). Orthostatic tolerance was determined by progressive LBNP to presyncope with continuous hemodynamic monitoring including PCWP and right atrial pressure. RESULTS LBNP tolerance was significantly lower in females than males (626.8 ± 55.0 vs. 927.7 ± 53.0 mmHg x min, P <0.01). Women had steeper slopes of the linear portion of Frank-Starling curves than men (12.5 ± 2.0 vs. 7.1 ± 1.5 ml/mmHg, P <0.05). During progressive LBNP, PCWP dropped quickly at low levels of LBNP, then more slowly and reached a plateau at high levels of LBNP near presyncope in all the subjects. At presyncope, SV was 35% and stroke index was 29% lower for the females compared with the males (both P <0.05). Coincident with the smaller SV, females had higher heart rates (P <0.05), but similar mean arterial pressures compared with males at the onset of presyncope. Vascular resistance was similar and plasma norepinephrine concentration did not differ between the genders. CONCLUSION These results suggest that lower orthostatic tolerance in women is associated with a smaller SV at any given cardiac filling pressure, rather than a lower responsiveness of vascular resistance during an orthostatic challenge. Thus, the Frank-Starling relationship may be an important mechanism underlying the gender difference in orthostatic tolerance. Supported by NASA SCORT grant NAGW-3582, and NASA OLMSA grant NAG5–4846.

Assessment of cerebrovascular and cardiovascular responses to lower body negative pressure as a test of cerebral autoregulation

The aim of this study was to determine whether lower body negative pressure (LBNP), combined with noninvasive methods of assessing changes in systemic and cerebral vascular resistance, is suitable as a method for assessing cerebral autoregulation. In 13 subjects we continuously assessed heart rate, blood pressure, cerebral blood flow velocity (CBFV) and cardiac output during graded levels of LBNP from 0 to −50 mm Hg. With increasing levels of LBNP, cardiac output declined significantly (to 55.8±4.5% of baseline value) but there was no overall change in mean arterial pressure. CBFV also fell at higher levels of LBNP (to 81.4±3.2% of baseline) but the percentage CBFV change was significantly less than that in cardiac output ( P<0.01). The maximum increase in cerebrovascular resistance (pulsatility ratio) was significantly less than that in total peripheral resistance (17±6% vs. 105±16%, P<0.01). Spectral analysis showed that the power of low-frequency oscillations in mean arterial pressure, but not CBFV, increased significantly at the −50 mm Hg level of LBNP. These results show that, even during high levels of orthostatic stress, cerebral autoregulation is preserved and continues to protect the cerebral circulation from changes in the systemic circulation. Furthermore, assessment of cardiovascular and cerebrovascular parameters during LBNP may provide a useful clinical test of cerebral autoregulation.

Effects of Lower Body Negative Pressure on Cardiac and Vascular Responses to Carotid Baroreflex Stimulation.

The aim of this study was to assess carotid baroreflex responses during graded lower body negative pressure (LBNP). In 12 healthy subjects (age 29±4 years) we applied sinusoidal neck suction (0 to –30 mmHg) at 0.1 Hz to examine the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Responses to neck suction were determined as the change in spectral power of RR-interval and blood pressure from baseline values. Measurements were carried out during progressive applications (0 to –50 mmHg) of LBNP. Responses to 0.1 and 0.2 Hz carotid baroreceptor stimulations during low levels of LBNP (–10 mmHg) were not significantly different from those measured during baseline. At higher levels of LBNP, blood pressure responses to 0.1 Hz neck suction were significantly enhanced, but with no significant change in the RR-interval response. LBNP at all levels had no effect on the RR-interval response to 0.2 Hz neck suction. The unchanged responses of RR-interval and blood pressure to neck suction during low level LBNP at –10 mmHg suggest no effect of cardiopulmonary receptor unloading on the carotid arterial baroreflex, since this LBNP level is considered to stimulate cardiopulmonary but not arterial baroreflexes. Enhanced blood pressure responses to neck suction during higher levels of LBNP are not necessarily the result of a reflex interaction but may serve to protect the circulation from fluctuations in blood pressure while standing.

Attenuated sympathetic nerve responses after 24 hours of bed rest.

Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.

Augmented cardiopulmonary and integrative sympathetic baroreflexes but attenuated peripheral vasoconstriction with age.

Based on observations of smaller increases in limb vascular resistance during acute incremental hypovolemia in older adults, cardiopulmonary and integrative (combined cardiopulmonary and arterial) baroreflex control of sympatho-circulatory function is thought to be impaired with aging in humans. We tested this hypothesis directly by making intraneural measurements of skeletal muscle sympathetic nerve activity (MSNA; peroneal microneurography) in groups of young (23+/-1 years; n=11) and older (64+/-1 years; n=12) healthy adult men during progressive hypovolemia produced by graded (-5 to -40 mm Hg) lower body negative pressure (LBNP). Baseline levels of MSNA and arterial blood pressure were higher and heart rate was lower in the older subjects (P<0.05). Lower levels of LBNP (-5 to -20 mm Hg) did not affect arterial blood pressure or heart rate in either group; systolic and pulse pressures declined during higher levels of LBNP (-30 and -40 mm Hg) but only in the young subjects (P<0.05). Graded LBNP evoked progressive, linear reductions in peripheral venous pressure (PVP) and increases in MSNA, plasma norepinephrine concentration (PNE), and forearm vascular resistance (FVR) in both groups (all P<0.05). DeltaMSNA/ deltaPVP was approximately 150% greater in the older versus young men during both lower and higher levels of hypovolemia (P<0.01); however, deltaFVR/deltaPVP was approximately 50% smaller in the older men (P<0.05). There was no difference in the MSNA-PNE relation with age, but deltaFVR/deltaMSNA was approximately 65% to 70% smaller in the older subjects (P<0.05). Our findings indicate that cardiopulmonary and integrative baroreflex control of central sympathetic outflow during hypovolemia is augmented, not impaired, with age in healthy humans. However, the reflex-mediated increases in limb vascular resistance during hypovolemia are smaller in older adults because of attenuated vasoconstrictor responsiveness to sympathetic stimulation.

Exercise training mode affects the hemodynamic responses to lower body negative pressure in women.

To determine if different exercise modes used to improve cardiovascular fitness result in differing cardiovascular responses to lower body negative pressure (LBNP) in exercise-trained women, seven chronically exercising female runners (RUN) and 11 swimmers (SWIM) of similar fitness levels maximal oxygen uptake, [VO(2max), mean (SEM) = 50 (2) and 45 (2) ml*kg(-1)*min(-1), respectively; P > 0.05] underwent serial exposures to LBNP at pressures of 0, -1.3, -2.7 and -5.3 kPa (referenced to ambient barometric pressure). Forearm vascular resistance (venous occlusion plethysmography) increased with LBNP but did not differ between groups at any level of LBNP. At 0 and - 1.3 kPa, the total peripheral resistance index (TPRI; impedance cardiography) was significantly (P <0.05) higher in RUN than SWIM [1.118(0.028) vs 0.787 (0.040) at 0 kPa and 1.245 (0.100) vs 0.840 (0.040) 2 kPa*l* min(-1)*m(-2) at -1.3kPa]. At an LBNP of -2.7kPa, stroke index (SI) was significantly higher in SWIM than RUN [57.8(4.6) vs 41.9 (4.0) ml*beat(-1)*m(-2)] while TPRI remained greater in RUN than SWIM. At -5.3 kPa, SWIM exhibited a higher cardiac index [3.232 (0.209) vs 2.447 (0.189) l*min(-1)*m(-2)] and SI [49.4 (4.4) vs 31.0 (4.5) ml *beat(-1)*m(-2)] but reduced heart rate [71(3) vs 83(5) beats . min(-1)] and TPRI [0.968 (0.043) vs 1.655 (0.128) kPa*1*min(-1)* m(-2)]. Mean arterial pressure declined significantly at an LBNP of -5.3 kPa in both groups; pulse pressure was lower (P <0.05) in RUN than SWIM at LBNP values of -2.7 and -5.3 kPa. These data suggest that: (1) female runners experience a greater increase in systemic vasoconstriction even though female swimmers can better maintain their cardiac index at high levels of LBNP, and (2) training mode appears to affect the pulse pressure responses to LBNP in exercise-trained women.

Lidocaine and Cardiovascular Reflex Responses to Simulated Orthostatic Stress in Normal Volunteers

The interactions of lidocaine with baroreceptor reflexes during simulated orthostatic stress or moderate volume depletion were investigated in healthy volunteers using the lower body negative pressure (LBNP) test. Cardiopulmonary baroreceptors were selectively unloaded at low levels of LBNP (-15 mm Hg) since the central venous pressure (CVP) decreased (-1.4 +/- 0.3 mm Hg) without changes in arterial pressure (AP) and heart rate (HR) but significant increases in forearm vascular resistance (FVR) and plasma noradrenaline (PNA). Cardiopulmonary as well as arterial baroreflexes were both unloaded at higher levels of LBNP (-40 mm Hg) since the CVP (-3.4 +/- 0.4 mm Hg) and systolic AP (-10 +/- 3 mm Hg) decreased whereas FVR, PNA, and plasma renin activity (PRA) increased further (all p less than 0.05). Following lidocaine infusion (serum level of 3.8 +/- 0.2 micrograms/ml), the AP, HR, FVR, and PNA increased and CVP decreased (p less than 0.05). Compared to LBNP performed under saline, lidocaine did not alter the LBNP (-15 mm Hg)-induced changes in cardiovascular and biological parameters but significantly decreased the induced rises in HR, FVR, PNA, and PRA at a LBNP of -40 mm Hg (p less than 0.05). In an additional study, it was also demonstrated that lidocaine significantly decreased the sensitivity of the reflex-mediated bradycardia following phenylephrine injection and attenuated the vasoconstrictor response to the cold pressor test taken as a nonspecific somatic pressor reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal responses to lower body negative pressure in humans

Renal blood flow, renal sympathetic nerve activity, assessed by the renal overflows of norepinephrine (NE), dopamine (DA), and neuropeptide Y-like immunoreactivity (NPY-LI), as well as plasma renin activity and angiotensin II (ANG II) were evaluated during stepwise increases in lower body negative pressure (LBNP) in 10 healthy volunteers. The fractional extraction of epinephrine (Epi) was used to assess renal catecholamine removal (approximately 50%) from arterial plasma. Renal NE, DA, and NPY-LI overflows at rest were 235 +/- 31, 30 +/- 5, and 0.6 +/- 0.2 pmol/min, respectively. LBNP increased renal vascular resistance (RVR) by 52% and renal NE overflow by 31%. Renin release increased by 330% (from 64 +/- 12 units/min) and arterial ANG II levels by 119%, without altering the renal ANG II extraction (which was approximately 50%). Renal DA and NPY-LI overflows were unaffected. A "vaso-vagal" reaction in one subject was associated with cessation of renal NE overflow and marked elevations of arterial Epi, renal renin release, and arterial ANG II. Selective unloading of cardiopulmonary baroreceptors by low-level LBNP did not affect RVR, whereas higher levels of LBNP caused renal vasoconstriction probably mediated in part by increased renal sympathetic nerve activity and in part by ANG II.

Relationship of cardiac chamber volume to baroreflex activity in normal humans.

The objectives of this study were to examine the effect of incremental lower body negative pressure (LBNP) on cardiac chamber volume and assess the relationship between cardiac chamber volume and baroreflex activation of the neurohormonal axis. Accordingly, echocardiographic determination of cardiac chamber volume and neurohormonal responses were studied in 14 normal subjects during incremental LBNP. LBNP -10 mm Hg decreased left atrial diameter and left ventricular systolic volume index, but did not alter heart rate, systolic or pulse pressure, or stroke volume. During LBNP -10 mm Hg, plasma norepinephrine levels increased, suggesting activation of the sympathetic nervous system. LBNP -40 mm Hg caused a significant decrease in left atrial diameter and left ventricular systolic, diastolic, and stroke volume indices. During LBNP -40 mm Hg, heart rate increased, and systolic and pulse pressure fell. With this more negative level of LBNP, norepinephrine, angiotensin II, aldosterone, and arginine vasopressin concentrations and PRA all increased. The findings that left atrial diameter decreased and plasma norepinephrine concentration increased during LBNP -10 mm Hg suggest that the sympathetic nervous system is sensitive to changes in atrial receptor activity. At higher levels of LBNP (-40 mm Hg), activation of the renin-angiotensin system and release of vasopressin were associated with a fall in left ventricular diastolic volume as well as a decrease in the pressure input to the arterial baroreceptors. Under this condition, the differential contribution of the cardiopulmonary and arterial baroreceptors to the regulation of the renin-angiotensin system and vasopressin release cannot be distinguished.

Physical fitness and hemodynamic response of women to lower body negative pressure

Aerobic fitness as assessed by maximal aerobic capacity (VO2max) has been shown to be associated with an attenuated baroreflex function during lower body negative pressure (LBNP) in men. Sixteen women (mean age = 24.7 yrs) were evaluated during progressive LBNP to -50 torr. Each subject's VO2max was determined using indirect calorimetry during the Bruce protocol exercise test. Eight subjects [mean VO2max = 56.8 (ml O2 X min-1) X kg-1] were designated as trained, and eight subjects [mean VO2max = 39.4 (ml O2 X min-1) X kg-1] were designated as untrained. During LBNP, heart rate, blood pressure, cardiac index, forearm blood flow, and leg circumference were measured. All subjects completed the LBNP protocol without clinical symptoms of pre-syncope. The over-all hemodynamic responses of both groups to LBNP were qualitatively similar to previous findings reported for males. However, no significant differences in response of hemodynamic variables were observed between trained and untrained subjects during LBNP to -50 torr (P greater than 0.05) except for vascular resistance and diastolic blood pressure at -50 torr where the untrained value was greater than the trained value. This would suggest that a fitness-related difference may have been present at higher levels of LBNP. Furthermore, in contrast to previous reports in males, the index of baroreflex responsiveness (delta heart rate/delta systolic blood pressure) was similar for both groups (P greater than 0.05). When these data were compared with a similar subject pool of males, the females displayed a significantly greater (P less than 0.05) tolerance of LBNP to -50 torr regardless of fitness.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of age and coronary heart disease on the circulatory responses to graded lower body negative pressure.

Previous reports have demonstrated that haemodynamic responses to various autonomic stresses such as head-up tilt, Valsalva's manoeuvre, face immersion, cold pressor, and static exercise are altered with increasing age and cardiac disease. In the present investigation, we compared the responses of 20 to 27 year old and 50 to 59 year old healthy men and 50 to 59 year old ambulatory coronary heart disease patients to graded lower body negative pressure (LBNP). Noninvasive methods including transthoracic impedance cardiography and venous occlusion plethysmography were used to monitor changes in stroke index, thoracic blood volume and vascular resistance. The tachycardia and stroke index decline of the older men and cardiac patients at higher levels of LBNP were similar but less than those of the younger men; we also noted greater increases in forearm and total peripheral resistance during LBNP in the two older groups than in the younger group. However, the decreases in thoracic blood volume were less in the two older groups at the higher levels of LBNP indicating that older subjects had been subjected to a lesser stress. These differences in thoracic blood volume displacement may be due to a decreased peripheral venous compliance in older subjects. When we compared responses to similar decreases in thoracic blood volume, the heart rate and stroke index changes were similar in the three groups but the exaggerated forearm vascular resistance and total peripheral resistance index increases in the older groups persisted. Our data suggest: (1) the decreased haemodynamic response to postural stress previously reported in older subjects and cardiac patients is due at least in part to a lesser peripheral sequestration of blood in the older individuals; (2) the lesser heart rate and stroke index responses in coronary heart disease patients to diminished preload stress may be due primarily to normal aging; and (3) the greater increases in peripheral vascular resistance in the two older groups during LBNP may be a function of the higher baseline resistance levels in these older subjects.