Cardiovascular responses to lower body negative pressure in trained and untrained older men.

To determine whether aerobic conditioning alters the orthostatic responses of older subjects, cardiovascular performance was monitored during graded lower body negative pressure in nine highly trained male senior athletes (A) aged 59-73 yr [maximum O2 uptake (VO2 max) = 52.4 +/- 1.7 ml.kg-1 x min-1] and nine age-matched control subjects (C) (VO2 max = 31.0 +/- 2.9 ml.kg-1 x min-1). Cardiac volumes were determined from gated blood pool scintigrams by use of 99mTc-labeled erythrocytes. During lower body negative pressure (0 to -50 mmHg), left ventricular end-diastolic and end-systolic volume indexes and stroke volume index decreased in both groups while heart rate increased. The decreases in cardiac volumes and mean arterial pressure and the increase in heart rate between 0 and -50 mmHg were significantly less in A than in C. For example, end-diastolic volume index decreased by 32 +/- 4 ml in C vs. 14 +/- 2 ml in A (P < 0.01), mean arterial pressure declined 7 +/- 5 mmHg in C and increased by 5 +/- 3 mmHg in A (P < 0.05), and heart rate increased 13 +/- 3 beats/min in C and 7 +/- 1 beats/min in A (P < 0.05). These data suggest that increased VO2 max among older men is associated with improved orthostatic responses.     

Leg mass and lower body negative pressure tolerance in men and women

To explore the hypothesis that lower body musclemass correlates with orthostatic tolerance, 18 healthy volunteers (age18-48 yr; 10 men, 8 women) underwent a graded lower body negativepressure (LBNP) protocol consisting of six, 5-min stages of suction up to 60 mmHg in 10-mmHg increments. Forearm blood flow, heart rate, andblood pressure were measured, and forearm vascular resistance wascalculated. Leg muscle mass was assessed by dual-energy X-ray absorptiometry. All subjects received standard intravenous hydration for at least 8 h before the study. Six men and four women completed allstages of LBNP. Four men and four women developed presyncopal symptoms,including marked bradycardia and/or hypotension, at LBNP levelsof 30 mmHg (n = 2; 1 man, 1 woman), 40 mmHg (n = 2; 1 man, 1 woman), and 50 mmHg (n = 4; 2 men, 2 women). Thepresyncopal subjects had leg muscle masses ranging from 19.5 to 25.2 kgin men and from 11.7 to 16.6 kg in women. In subjects who completed allstages of LBNP, leg muscle mass ranged from 17.5 to 24.1 kg in men andfrom 10.4 to 18.0 kg in women. Leg muscle mass did not differ betweenpresyncopal subjects and those who completed the protocol. Furthermore,there were no differences in the hemodynamic responses to LBNP betweensubjects with low vs. high leg mass. These data suggest that leg musclemass is not a critical determinant of LBNP tolerance in otherwisehealthy men and women.

     

Cardiac responses to lower body negative pressure and dynamic leg exercise

Cardiac responses to dynamic leg exercise at 0, 50, and 100 W in the supine position were investigated with and without the lower portion of the body exposed to a pressure of -6.6 kPa (Lower Body Negative Pressure, LBNP). Resting values for heart rate (HR) and stroke volume (SV) were considerably higher and lower, respectively, during LBNP than in the control condition. At the transition from rest to the mildest exercise during LBNP SV showed a prompt increase by about 40%, but no significant change in the control condition. HR, which increased by 17 beats X min-1 in the control condition, showed during LBNP no change initially and subsequently a small but significant drop below its resting value. Steady-state values for HR at the various levels of exercise were not significantly affected by LBNP, whereas corresponding values for SV were considerably lowered, so that exercise values for cardiac output were about 3 l X min-1 less during LBNP than in the control condition. The reductions in SV and cardiac output indicate residual pooling of blood in intra- and extramuscular capacitance vessels of the legs. With a change from rest to exercise at 100 W during LBNP mean systolic ejection rate (MSER) increased by 67%, the relations between SV and MSER suggesting that ventricular performance was maintained by a combination of the Frank-Starling mechanism and enhanced contractile strength.     

Venous and arterial reflex responses to positive-pressure breathing and lower body negative pressure

Peters, Jochen K., George Lister, Ethan R. Nadel, and GaryW. Mack. Venous and arterial reflex responses to positive-pressure breathing and lower body negative pressure. J. Appl.Physiol. 82(6): 1889-1896, 1997.We examined therelative importance of arteriolar and venous reflex responses duringreductions in cardiac output provoked by conditions that increase[positive end-expiratory pressure (PEEP)] or decrease[lower body negative pressure (LBNP)] peripheral venous filling.Five healthy subjects were exposed to PEEP (10, 15, 20, and 25 cmH₂O) and LBNP (10,15, 20, and 25 mmHg) to induce progressive butcomparable reductions in right atrial transmural pressure (control tominimum): from 5.9 ± 0.4 to 1.8 ± 0.7 and from 6.5 ± 0.6 to2.0 ± 0.2 mmHg with PEEP and LBNP, respectively. Cardiac output(impedance cardiography) fell less during PEEP than during LBNP (from3.64 ± 0.21 to 2.81 ± 0.21 and from 3.39 ± 0.21 to 2.14 ± 0.24 l · min¹ · m²with PEEP and LBNP, respectively), and mean arterial pressure increased. We observed sustained increases in forearm vascular resistance (i.e., forearm blood flow by venous occlusionplethysmography) and systemic vascular resistance that were greaterduring LBNP: from 19.7 ± 2.91 to 27.97 ± 5.46 and from 20.56 ± 2.48 to 50.25 ± 5.86 mmHg · ml¹ · 100 mltissue¹ · min(P < 0.05) during PEEP and LBNP,respectively. Venomotor responses (venous pressure in thehemodynamically isolated limb) were always transient, significant onlywith the greatest reduction in right atrial transmural pressure, andwere similar for LBNP and PEEP. Thus arteriolar rather than venousresponses are predominant in blood volume mobilization from skin andmuscle, and venoconstriction is not intensified with venous engorgementduring PEEP.

     

Age- and fitness-related differences in limb venous compliance do not affect tolerance to maximal lower body negative pressure in men and women.

Aging and chronic exercise training influence leg venous compliance. Venous compliance affects responses to an orthostatic stress; its effect on tolerance to maximal lower body negative pressure (LBNP) in the elderly is unknown. The purpose of this study was to determine the influence of age and fitness, a surrogate measure of exercise training, on calf venous compliance and tolerance to maximal LBNP in men and women. Forty participants, 10 young fit (YF; age = 22.6 +/- 0.5 yr, peak oxygen uptake = 57.1 +/- 2.0 ml.kg(-1).min(-1)), 10 young unfit (YU; 23.1 +/- 1.0 yr, 41.1 +/- 2.0 ml.kg(-1).min(-1)), 10 older fit (OF; 73.9 +/- 2.0 yr, 39.0 +/- 2.0 ml.kg(-1).min(-1)), and 10 older unfit (OU; 70.9 +/- 1.6 yr, 27.1 +/- 2.0 ml.kg(-1).min(-1)), underwent graded LBNP to presyncope or 4 min at -100 mmHg. By utilizing venous occlusion plethysmography, calf venous compliance was determined by using the first derivative of the pressure-volume relation during cuff pressure reduction. We found that the more fit groups had greater venous compliance than their unfit peers (P < 0.05) as did the young groups compared with their older peers (P < 0.05) such that OU < YU = OF < YF. LBNP tolerance did not differ between groups. In conclusion, these data suggest that aging reduces, and chronic exercise increases, venous compliance. However, these data do not support a significant influence of venous compliance on LBNP tolerance.     

Comparison of cardiovascular responses between lower body negative pressure and head-up tilt.

To investigate local blood-flow regulation during orthostatic maneuvers, 10 healthy subjects were exposed to -20 and -40 mmHg lower body negative pressure (LBNP; each for 3 min) and to 60 degrees head-up tilt (HUT; for 5 min). Measurements were made of blood flow in the brachial (BF(brachial)) and femoral arteries (BF(femoral)) (both by the ultrasound Doppler method), heart rate (HR), mean arterial pressure (MAP), cardiac stroke volume (SV; by echocardiography), and left ventricular end-diastolic volume (LVEDV; by echocardiography). Comparable central cardiovascular responses (changes in LVEDV, SV, and MAP) were seen during LBNP and HUT. During -20 mmHg LBNP, -40 mmHg LBNP, and HUT, the following results were observed: 1) BF(brachial) decreased by 51, 57, and 41%, and BF(femoral) decreased by 40, 53, and 62%, respectively, 2) vascular resistance increased in the upper limb by 110, 147, and 85%, and in the lower limb by 76, 153, and 250%, respectively. The increases in vascular resistance were not different between the upper and lower limbs during LBNP. However, during HUT, the increase in the lower limb was much greater than that in the upper limb. These results suggest that, during orthostatic stimulation, the vascular responses in the limbs due to the cardiopulmonary and arterial baroreflexes can be strongly modulated by local mechanisms (presumably induced by gravitational effects).     

Reflex responses to regional venous pooling during lower body negative pressure in humans

Halliwill, John R., Lori A. Lawler, Tamara J. Eickhoff,Michael J. Joyner, and Sharon L. Mulvagh. Reflex responses toregional venous pooling during lower body negative pressure in humans.J. Appl. Physiol. 84(2): 454-458, 1998.Lower body negative pressure is frequently used to simulateorthostasis. Prior data suggest that venous pooling in abdominal orpelvic regions may have major hemodynamic consequences. Therefore, we developed a simple paradigm for assessing regional contributions tovenous pooling during lower body negative pressure. Sixteen healthy menand women underwent graded lower body negative pressure protocols to 60 mmHg while wearing medical antishock trousers to prevent venous poolingunder three randomized conditions:1) no trouser inflation (control),2) only the trouser legs inflated, and 3) the trouser legs andabdominopelvic region inflated. Without trouser inflation, heart rateincreased 28 ± 4 beats/min, mean arterial pressure fell 3 ± 2 mmHg, and forearm vascular resistance increased 51 ± 9 units at 60 mmHg lower body negative pressure. With inflation of eitherthe trouser legs or the trouser legs and abdominopelvic region, heartrate and mean arterial pressure did not change during lower bodynegative pressure. By contrast, although the forearm vasoconstrictorresponse to lower body negative pressure was attenuated by inflation ofthe trouser legs (forearm vascular resistance 33 ± 10 units,P < 0.05 vs. control), attenuation was greater with the inflation of the trouser legs and abdominopelvic region (forearm vascular resistance 16 ± 5 units,P < 0.05 vs. control and trouserlegs-only inflation). Thus the hemodynamic consequences of pooling inthe abdominal and pelvic regions during lower body negative pressureappear to be less than in the legs in healthy individuals.

     

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.     

Effect of hindlimb suspension on cardiovascular responses to sympathomimetics and lower body negative pressure

To determine whether hindlimb suspension is associated with the development of cardiovascular deconditioning, male rats were studied before and after undergoing one of three treatment conditions for 9 days: 1) cage control (n = 15, CON), 2) horizontal suspension (n = 15, HOZ), and 3) head-down suspension (n = 18, HDS). Testing included lower body negative pressure administered during chloralose-urethan anesthesia and graded doses of sympathomimetic agents (norepinephrine, phenylephrine, and tyramine) administered to conscious unrestrained animals. Both HDS and HOZ were associated with a small decrease in the hypotensive response to lower body negative pressure. The HOZ group, but not the HDS group, exhibited augmented reflex tachycardia. Furthermore, both HDS and HOZ groups manifested reduced pressor responses to phenylephrine after treatment. These reductions were associated with significantly attenuated increases in mesenteric vascular resistance. However, baroreflex control of heart rate was not altered by the treatment conditions. Collectively, these results indicate that 9 days of HDS in rats does not elicit hemodynamic response patterns generally associated with cardiovascular deconditioning induced by hypogravic conditions.     

Effect of 6-week endurance training on hemodynamic and neurohormonal responses to lower body negative pressure (LBNP) in healthy young men.

Endurance training is considered as a factor impairing orthostatic tolerance although an improvement and lack of effect have been also reported. The mechanisms of the changes and their relation to initial tolerance of orthostasis are not clear. In the present study, effect of moderate running training on hemodynamic and neurohormonal changes during LBNP, a laboratory test simulating orthostasis, was investigated in subjects with high (HT) and low (LT) tolerance of LBNP. Twenty four male, healthy subjects were submitted to graded LBNP (-15, -30 and -50 mmHg) before and after training. During each test heart rate (HR), stroke volume (SV) and blood pressure, plasma catecholamines, ACTH, adrenomedullin, atrial natriuretic peptide, and renin activity were determined. Basing on initial test, 13 subjects who withstood LBNP at -50 mmHg for 10 min were allocated into HT group and 11 subjects who earlier showed presyncopal symptoms to LT group. Training improved LBNP tolerance in six LT subjects. This was associated with attenuated rate of HR increase and SV decline (before training, at -30 mmHg deltaHR was 21 +/- 4 beats/min and deltaSV - -36+/- 8 ml while after training the respective values were 8 +/- 4 beats/min and -11+/- 6 ml). No differences in hemodynamic response were found in HT subjects and those from LT group whose LBNP tolerance was unchanged. In neither group training affected neurohormonal changes except inhibition of plasma ACTH rise in subjects with improvement of LBNP tolerance. It is concluded that some subjects with low orthostatic tolerance may benefit from moderate training due to improvement of cardiac function regulation.     

Effects of a 6-mo endurance-training program on venous compliance and maximal lower body negative pressure in older men and women.

Aging and chronic exercise training influence leg venous compliance. Venous compliance affects responses to an orthostatic stress. The extent to which exercise training in a previously sedentary older population will affect venous compliance and tolerance to the simulated orthostatic stress of maximal lower body negative pressure (LBNP) is unknown. The purpose of this investigation is to determine the influence of a 6-mo endurance-training program on calf venous compliance and responses and tolerance to maximal LBNP in older men and women. Twenty participants (exercise group: n = 10, 5 men, 5 women; control group: n = 10, 6 men, 4 women; all >60 yr) underwent graded LBNP to presyncope or 4 min at -100 mmHg before and after a 6-mo endurance-training program. Utilizing venous occlusion plethysmography, calf venous compliance was determined in both groups using the first derivative of the pressure-volume relation during cuff pressure reduction before training, at 3 mo, and at the end of the training program. The exercise group improved their fitness with the 6-mo endurance-training program, whereas the control group did not change (14 +/- 3 vs. <1 +/- 2%; P < 0.05). LBNP tolerance did not differ between groups or across trials (P = 0.47). Venous compliance was not different between groups or trials, either initially or after 3 mo of endurance training, but tended to be greater in the exercise group after 6 mo of training (P = 0.08). These data suggest that a 6-mo endurance-training program may improve venous compliance without affecting tolerance to maximal LBNP in older participants.     

Effects of leg venous hemodynamics on cardiovascular responses to lower body negative pressure and aging

In aged people, decreases in stroke volume and cardiac output during orthostatic challenge are less. It is suggested that the stiffness of blood vessels is greater in the elderly, blunting leg venous pooling and drop in central blood volume in an upright position. Leg venous hemodynamics plays an important role in human cardiovascular homeostasis against gravitational stress. This study aimed to clarify how aging influences the leg venous hemodynamics and its contribution to cardiovascular homeostasis during lower body negative pressure (LBNP) in humans.     

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.     

Hemodynamic and neuroendocrine predictors of lower body negative pressure (LBNP) intolerance in healthy young men.

Exposure to LBNP results in body fluid shift to lower extremities similarly as under influence of orthostatic stress. In susceptible persons it leads to syncope. For better understanding why certain individuals are more susceptible to orthostatic challenges it seemed necessary to collect more data on hemodynamic and neuroendocrine adjustments occurring before onset of presyncopal symptoms Accordingly, in this study heart rate (HR), blood pressure (BP), stroke volume (SV), cardiac output (CO), hematocrit, plasma catecholamines, adrenomedullin, ACTH and plasma renin activity (PRA) were measured in 24 healthy men during graded LBNP (-15, -30 and -50 mmHg). Thirteen subjects completed the test (HT group) whereas 11 had presyncope signs or symptoms at -30 mmHg or at the beginning of -50 mmHg (LT group). Comparison of these groups showed that LT subjects had lower baseline total peripheral resistance and higher plasma adrenomedullin. During LBNP plasma catecholamine and PRA increases were even greater in LT than in HT group while plasma adrenomedullin elevations were similar in both groups. Plasma ACTH increased only in LT group following presyncope symptoms. Low tolerant group showed more rapid decline of SV and CO than HT subjects from the beginning of LBNP. It is suggested that measurements of SV at the level of LBNP which did not evoke any adverse symptoms may be of predictive value for lower orthostatic tolerance.     

Lower body negative pressure exercise plus brief postexercise lower body negative pressure improve post-bed rest orthostatic tolerance.

Orthostatic intolerance follows actual weightlessness and weightlessness simulated by bed rest. Orthostasis immediately after acute exercise imposes greater cardiovascular stress than orthostasis without prior exercise. We hypothesized that 5 min/day of simulated orthostasis [supine lower body negative pressure (LBNP)] immediately following LBNP exercise maintains orthostatic tolerance during bed rest. Identical twins (14 women, 16 men) underwent 30 days of 6 degrees head-down tilt bed rest. One of each pair was randomly selected as a control, and their sibling performed 40 min/day of treadmill exercise while supine in 53 mmHg (SD 4) [7.05 kPa (SD 0.50)] LBNP. LBNP continued for 5 min after exercise stopped. Head-up tilt at 60 degrees plus graded LBNP assessed orthostatic tolerance before and after bed rest. Hemodynamic measurements accompanied these tests. Bed rest decreased orthostatic tolerance time to a greater extent in control [34% (SD 10)] than in countermeasure subjects [13% (SD 20); P < 0.004]. Controls exhibited cardiac stroke volume reduction and relative cardioacceleration typically seen after bed rest, yet no such changes occurred in the countermeasure group. These findings demonstrate that 40 min/day of supine LBNP treadmill exercise followed immediately by 5 min of resting LBNP attenuates, but does not fully prevent, the orthostatic intolerance associated with 30 days of bed rest. We speculate that longer postexercise LBNP may improve results. Together with our earlier related studies, these ground-based results support spaceflight evaluation of postexercise orthostatic stress as a time-efficient countermeasure against postflight orthostatic intolerance.