Levels Of Lower Body Negative Pressure Research Articles

Comparison of muscle sympathetic responses to hemorrhage and lower body negative pressure in humans

We compared changes in muscle sympathetic nerve activity (SNA) during graded lower body negative pressure (LBNP) and 450 ml of hemorrhage in nine healthy volunteers. During LBNP, central venous pressure (CVP) decreased from 6.1 +/- 0.4 to 4.5 +/- 0.5 (LBNP -5 mmHg), 3.4 +/- 0.6 (LBNP -10 mmHg), and 2.3 +/- 0.6 mmHg (LBNP -15 mmHg), and there were progressive increases in SNA at each level of LBNP. The slope relating percent change in SNA to change in CVP during LBNP (mean +/- SE) was 27 +/- 11%/mmHg. Hemorrhage of 450 ml at a mean rate of 71 +/- 5 ml/min decreased CVP from 6.1 +/- 0.5 to 3.7 +/- 0.5 mmHg and increased SNA by 47 +/- 11%. The increase in SNA during hemorrhage was not significantly different from the increase in SNA predicted by the slope relating percent change in SNA to change in CVP during LBNP. These data show that nonhypotensive hemorrhage causes sympathoexcitation and that sympathetic responses to LBNP and nonhypotensive hemorrhage are similar in humans.

Effects of Preload Reduction on Left Atrial Pump Function in Hypertrophic Cardiomyopathy and Myocardial Infarction

To characterize the preload dependence of augmented left-atrial pump function in left-ventricular dysfunction, the changes in the transmitral flow velocity pattern induced by a lower-body negative pressure (LBNP) of –20 and –40 mm Hg were investigated in 19 patients with hypertrophic cardiomyopathy, 17 patients with myocardial infarction and 19 control subjects. The maximal early diastolic flow velocity and early diastolic flow velocity integral decreased with –20 mm Hg LBNP, with even greater decreases occurring with –40 mm Hg LBNP in all groups. The extent of the changes did not significantly differ between the three groups. On the other hand, the maximal late diastolic flow velocity and late diastolic flow velocity integral tended to decrease only in the patients with hypertrophic cardiomyopathy, whereas these indices were unchanged at any level of LBNP in the patients with myocardial infarction and control subjects. The late diastolic filling fraction tended to increase in all groups in proportion with the intensity of the negative pressure, but the extent of the changes was significantly smaller in the patients with hypertrophic cardiomyopathy than in those with myocardial infarction or control subjects. These results suggested that left-atrial performance decreases due to LBNP-induced preload reduction in patients with hypertrophic cardiomyopathy, whereas no change is seen in patients with myocardial infarction or control subjects.

Sympathetic activity during graded central hypovolemia in hypoxemic humans

To determine how hypoxemia (Hx) might alter muscle sympathetic nerve activity (MSNA) (microneurography, peroneal nerve), norepinephrine (NE) levels, and vasoconstriction during mild central hypovolemia, we exposed eight men to continuous graded lower body negative pressure (LBNP) (-5, -10, -15, -20, and -25 mmHg, 5 min per level) during both Hx (10 or 12% O2) and normoxia (Nx). Hx significantly augmented MSNA during LBNP. Total MSNA (average amplitude X burst frequency) rose at each level of LBNP by 2, 28, 93, 61, and 123% (Nx) and 32, 110, 127, 179, and 216% (Hx). Only at LBNP -20 and -25 mmHg did Hx significantly augment the increase in forearm venous NE concentration. Arterial pressure was unaffected by LBNP in Nx and Hx. Forearm blood flow (venous occlusion plethysmography) fell, and forearm vascular resistance (FVR) rose 23, 53, 65, 67, and 86% (Nx) vs. 22, 23, 60, 69, and 87% (Hx), but increments in FVR (absolute units) were significantly less in Hx. Correlations among MSNA and other variables were insignificant for pooled data owing to large inter-individual variations in slopes, but correlations were significant for total MSNA (and burst frequency) vs. FVR (Nx) and NE (Hx). Three men released epinephrine during LBNP; this was accompanied by forearm vasodilation and falling pressure, and in two men, decreased MSNA and bradycardia occurred (i.e., vasovagal reaction). Overall, we found no major defect in sympathetic control during graded hypovolemia and Hx as long as epinephrine levels did not rise.

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.

Baroreflex control of muscle sympathetic nerve activity in borderline hypertension.

Patients with borderline hypertension have exaggerated vascular responses to orthostatic stress produced by tilt or lower body negative pressure (LBNP). It has been suggested that 1) in the supine position, these patients have augmented activity of cardiopulmonary baroreceptors that exerts an increased restraint on sympathetic vasoconstrictor tone; 2) withdrawal of this augmented inhibitory baroreceptor activity during orthostatic stress elicits augmented reflex sympathetic vasoconstrictor outflow; and 3) augmented cardiopulmonary baroreceptor activity may be secondary to impaired arterial baroreflex mechanisms. To test these hypotheses, we recorded muscle sympathetic nerve activity from the peroneal nerve in seven borderline hypertensive subjects and seven age-, sex-, and weight-matched normotensive subjects during three levels of nonhypotensive LBNP and infusions of phenylephrine and nitroprusside. During LBNP, reductions of central venous pressure were similar in borderline hypertensive and normotensive subjects, and arterial pressure and heart rate values were unchanged. Increases of sympathetic nerve activity, however, were significantly greater in borderline hypertensive than in normotensive subjects at each level of LBNP, indicating an augmented gain of the cardiopulmonary baroreflex. To determine whether this augmentation is related to impairment of arterial baroreflexes, we measured changes of sympathetic nerve activity during increases and decreases of arterial pressure produced with infusions of intravenous phenylephrine and nitroprusside. Central venous pressure was held at control levels by LBNP during phenylephrine and saline infusion during nitroprusside. Changes of sympathetic nerve activity during alterations of arterial pressure were similar in borderline hypertensive and normotensive subjects. These data show that cardiopulmonary baroreflex control of SNA is augmented in borderline hypertensive subjects and that this augmentation does not result from an attenuation of the arterial baroreflex.

Blunted sympathetic response to cardiopulmonary receptor unloading in hypertensive patients with left ventricular hypertrophy. A possible compensatory role of atrial natriuretic factor.

To investigate whether or not hypertension with left ventricular hypertrophy (LVH) modifies the mechanisms underlying the vascular adjustments to orthostatic stress, we evaluated the hemodynamic and hormonal effects of graded lower-body negative pressure (LBNP) (-10 and -40 mm Hg) before and after sympathetic blockade in 10 hypertensive patients with LVH and in five age- and sex-matched normotensive subjects. In control conditions, LBNP elicited comparable vasoconstrictor responses in the forearm in the two groups. In normotensive subjects, graded increases in plasma norepinephrine and plasma renin activity (PRA) and reductions in plasma immunoreactive atrial natriuretic factor (irANF) were recorded. In hypertensive patients, a significant increase in plasma norepinephrine and plasma renin activity was obtained only with the higher level of LBNP, whereas irANF plasma levels decreased progressively. In both groups, sympathetic blockade abolished the increase in plasma renin activity and did not modify the changes in plasma irANF induced by both levels of LBNP in control conditions. The vascular response to -10 mm Hg LBNP remained unchanged after sympathetic blockade in both groups. However, after sympathetic blockade, the vasoconstrictor response to -40 mm Hg LBNP in normal subjects was no longer different from that elicited by -10 mm Hg LBNP, whereas in hypertensive patients the vasoconstrictor response was still significantly higher than that induced by -10 mm Hg LBNP. Direct correlations between the percent changes in forearm vascular resistance and those in plasma norepinephrine and plasma renin activity were found only in normal subjects in control conditions but were not observed after sympathetic blockade. On the contrary, the inverse correlation between changes in irANF plasma levels and in forearm vascular resistance found in control conditions in both groups was still observed after sympathetic blockade. In a separate group of hypertensive patients with left ventricular hypertrophy, exogenous infusion of ANF induced an increase in venous irANF plasma levels of the same magnitude of the decrease evoked by LBNP and significantly reduced forearm vascular resistance. These data show that in hypertensive patients with left ventricular hypertrophy, sympathetic activation does not contribute to the vascular response to cardiopulmonary receptor unloading (-10 mm Hg LBNP). They also suggest that in these patients inhibition of ANF secretion may play a role in the response to a low level of LBNP so that the peripheral vasoconstriction induced by cardiopulmonary receptor unloading is comparable to that observed in normal subjects despite the lack of appropriate sympathetic reflex vasoconstriction.

Atrial Natriuretic Peptide Attenuates the Reflex Sympathetic Responses to Lower Body Negative Pressure

The authors studied the effect of intravenous infusion of atrial natriuretic peptide (ANP) on the plasma catecholamine and forearm vasoconstrictor responses to cardiopulmonary baroreflex deactivation in six normal, male volunteers in order to determine whether ANP influences reflex forearm vasoconstriction in humans. Unloading of low-pressure cardiopulmonary baroreceptors (CPBR) was accomplished by application of low levels (-10 and -20 mm Hg) of lower body negative pressure (LBNP). The authors measured the plasma norepinephrine (NE) and epinephrine, the mean arterial pressure (MAP), and the forearm vascular resistance (FVR) responses to reflex sympathetic activation by LBNP. ANP infusion (0.1 microgram.kg-1.min-1) decreased (p less than 0.01) basal MAP, as well as plasma renin activity and plasma aldosterone levels (p less than 0.05). ANP infusion also reduced (p less than 0.01) plasma NE responses to both levels of LBNP and tended to decrease both epinephrine and FVR during ANP infusion at -20 mm Hg LBNP (p = 0.8). These data suggest that exogenous ANP inhibits the reflex sympathetic responses that occur with CPBR unloading. The blunted plasma NE responses to CPBR unloading parallel the attenuation of FVR response to LBNP during ANP infusion, despite significant LBNP-induced hypotension.

Baroreceptor sensitivity in prehypertensive young adults.

Decreased baroreceptor reflex sensitivity has been implicated in the pathogenesis of hypertension. The purpose of this study is to determine if alterations of baroreceptor function precede the development of hypertension in humans. Baroreceptor function was evaluated in 13 young adult white men with relatively high blood pressures sustained for 12 to 15 years and 12 age-matched men with sustained relatively low blood pressures. High pressure baroreceptor activity was evaluated by measuring change in pulse interval in response to decreases and increases of arterial pressure, induced by graded infusions of nitroprusside and angiotensin II, respectively. In response to both agents, baroreceptor slopes did not differ in the high and low blood pressure groups. Plasma norepinephrine also increased similarly in both blood pressure groups in response to nitroprusside. To study low-pressure baroreceptor function, responses to graded levels of lower-body negative pressure (LBNP) were measured. Comparing both blood pressure groups, there were similar increases of heart rate, total peripheral resistance, and plasma norepinephrine in response to LBNP. Both blood pressure groups also had similar increases of heart rate and blood pressure in response to isometric (handgrip) exercise. Thus, high-pressure and low-pressure baroreceptor function is not altered in prehypertensive young adults. However, continued follow-up will be required to determine if these individuals with sustained relatively high blood pressures are truly prehypertensive.

Reflex effects of prolonged cardiopulmonary baroreceptor unloading in humans.

Most studies of the reflex responses to cardiopulmonary baroreceptor unloading with lower body negative pressure (LBNP) have assessed responses during the first few minutes of LBNP. It is unknown if these early changes are representative of the steady state. Thus we determined the response of heart rate, arterial pressure, forearm vascular resistance (FVR), and plasma norepinephrine (NE), renin (PRA), and aldosterone to prolonged (20 min) LBNP in nine normal subjects. All measurements were obtained at base line and after 3, 10, and 20 min of LBNP (-10, -20, and -40 mmHg). A 20-min recovery period was interposed between each period of LBNP. The heart rate and mean arterial pressure responses to LBNP during all levels of suction were not significantly different at 3, 10, and 20 min of continuous suction. Changes in FVR at 3, 10, and 20 min, respectively, were 18.4 +/- 3.2, 26.3 +/- 4.2, and 19.6 +/- 4.2 U during LBNP -10 mmHg; 33 +/- 7, 30.5 +/- 7.6, and 30 +/- 5.2 U during LBNP -20 mmHg; and 53.6 +/- 11.7, 57 +/- 8.8, and 49.4 +/- 12 during LBNP -40 mmHg, thus indicating a near maximal vasoconstrictor response at 3 min that was sustained throughout the 20 min during all levels of LBNP. Plasma NE rose to near peak level by 3 min. However, PRA and aldosterone changed significantly only after 20 min during LBNP at -10 and -20 mmHg. These data indicate that LBNP activates the sympathetic nervous system early, whereas activation of the renin-angiotensin-aldosterone axis is delayed. Our data should be taken into consideration in the design of future investigations of reflex neurohumoral responses to LBNP.

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)

Beta blockade in the compensation for bed-rest cardiovascular deconditioning: Physiologic and pharmacologic observations

Beta-adrenergic blockade using intravenous propranolol was evaluated as a countermeasure for bed-rest-induced cardiovascular deconditioning. After propranolol administration, tolerance to a maximal lower body negative pressure (LBNP) test after bed rest improved to at least the −70 mm Hg level; following this, there was a sharp decrease in tolerance time. Propranolol decreased mean tolerance time by 36% (17.7 ± 2.4 to 11.5 ± 2.3 minutes) before bed rest, and by only half as much (16.6%) after bed rest (14.4 ± 2.2 to 12.0 ± 2.3 minutes). Systemic vascular resistance was maintained and even slightly increased after propranolol despite a decrease in cardiac output, indicating β 2-adrenergic blockade. Heart rates at all levels of LBNP were lower during β blockade, yet increases occurred with successive LBNP steps, both before and after bed rest, indicating withdrawal of parasympathetic nervous system influences. Results support the use of propranolol in small dosages as a countermeasure after bed rest, and the findings may also be extrapolated to space-flight deconditioning.

Effect of temperature and baroreceptor stimulation on reflex venomotor responses.

To investigate the interaction of thermal reflexes and baroreflexes in the control of the peripheral veins, we studied in supine humans the effects of lower body negative pressure (LBNP) and neck suction (NS) on forearm veins at ambient temperatures (Ta) of 18, 28, and 37 degrees C. Forearm venous volume (FVV)-venous pressure (FVP) relations (forearm venous capacitance) on six subjects showed an increase from 18 through 28 to 37 degrees C (P less than 0.001). Heart rate increased (P less than 0.001) and forearm venous capacitance decreased (P less than 0.001) in proportion to the level of LBNP applied from 20 to 50 Torr at all Ta. At 50 Torr LBNP, FVV at 30 cmH2O, FVP decreased from control values of 2.5, 3.8, and 4.4 to 1.6, 2.7, and 3.4 ml/100 ml at 18, 28, and 37 degrees C, respectively. We also studied venomotor responses using the occluded limb technique. Although LBNP caused venoconstriction, NS applied either alone or during LBNP produced no change in venomotor tone. Therefore we concluded that carotid baroreceptors play little role in reflex venomotor adjustments. Since changes in mean arterial and pulse pressures during LBNP did not account for the observed venomotor responses, we concluded that low-pressure baroreceptors initiate significant venoconstrictor reflexes over a wide range of Ta.

Response of vasopressin and norepinephrine to lower body negative pressure in humans.

To examine the contributions of cardiopulmonary and sinoaortic baroreceptors to the nonosmotic release of arginine vasopressin (AVP) in normal humans, we subjected nine individuals without evidence of hypertension or heart disease to graded, lower body negative pressure (LBNP). We also studied the effects of this maneuver on sympathetic nervous system activity using plasma norepinephrine (NE) as an index. Heart rate (HR), mean arterial pressure (MAP), pulse pressure (PP), and central venous pressure (CVP) were measured in the control state and during two consecutive levels of increasingly intense LBNP. At each stage blood was sampled for AVP and NE. AVP was analyzed by radioimmunoassay, NE by a radioenzymatic method. During the first level of LBNP, CVP decreased with no change in HR, MAP, or PP. NE increased from 147 +/- 47 to 212 +/- 53 (SD) pg/ml, P less than 0.01, whereas AVP (5.0 +/- 1.0 pg/ml) did not change. With increased suction CVP fell further, HR increased, and PP narrowed, but MAP did not change. NE further increased to 291 +/- 58 pg/ml (P less than 0.01), but AVP still did not change significantly. One subject became markedly hypotensive, and his AVP increased from 2.6 to 81 pg/ml. A fall in CVP that results in sympathetic activation presumably via cardiopulmonary receptors does not therefore increase AVP levels; a further fall in CVP that leads to modest unloading of the sinoaortic baroreceptor and further increased sympathetic activity also fails to stimulate AVP. Hypotension, however, is accompanied by a rapid and profound increase in circulating AVP.

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.

Summated circulatory responses of thermal and baroreflexes in humans.

Baroreceptor and thermal receptor mediated reflexes are important neural control systems that can markedly alter blood pressure in humans. These two systems have different afferent limbs and are integrated at different central sites. Although the circulatory effects of activating these individual reflexes have been examined, the effects of simultaneous activation of two or more separate reflexes have received relatively little attention. We used noninvasive methods in 13 normal men (20-27 yr) to examine the responses mediated by cardiopulmonary and arterial baroreceptors; the reflexes were elicited by alterations in central blood volume [lower body negative pressure (LBNP) and leg elevation (LE)] in the presence or absence of local thermal receptor stimulation induced by hand immersion (HI) in 10 degree C water. During all levels (-10, -25, and -40 Torr) of LBNP and during LE, forearm vascular resistance (FVR) was altered. At the two higher levels of LBNP, stroke volume, cardiac index, and blood pressure (BP) decreased, and heart rate (HR) and total peripheral resistance (TPR) increased. TPR, FVR, and BP increased during HI. Our analyses indicated that responses to combined stimuli, i.e., local cold during LBNP or LE, resulted in simple additive responses in all variables except HR. A central interaction between thermal and baroreflex control of HR is possible.

A new application of LBNP to measure orthostatic tolerance before and after 0-g simulation (water immersion)

Lower body negative pressure (LBNP) remains an important device for the generation of orthostatic stress in the space flight environment as well as a tool to measure inflight and postflight changes in orthostatic response. These applied levels of LBNP have typically not exceeded 50–60 mm Hg negative pressure. Information is incomplete as to the levels of absolute LBNP orthostatic tolerance, and the factors responsible for their variance. A better definition of the tolerance limits for males and females could be expected to aid the evaluation of lower levels of LBNP. An LBNP device was built to study absolute orthostatic tolerance; additionally, another LBNP device was constructed to permit orthostatic tolerance testing directly after a controlled water immersion period. Absolute LBNP orthostatic tolerance patterns are analyzed for a group of males and females (series I). A preliminary statement on the variations of LBNP orthostatic tolerance after limited periods of water immersion and bed rest is also provided (series II).