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 posture on cardiovascular responses to lower body positive pressure at rest and during dynamic exercise

We tested thehypothesis that cardiovascular responses to lower body positivepressure (LBPP) would be dependent on the posture of the subject andalso on the background condition (rest or exercise). We measured heartrate (HR), mean arterial blood pressure (MAP), and cardiac strokevolume in eight subjects at rest and during cycle ergometer exercise(76 ± 3 W) with and without LBPP (25, 50, and 75 mmHg) inthe supine and upright positions. At rest, the increase in MAP wasproportional to the increase in LBPP and was greater in the supine (6 ± 2, 15 ± 3, and 26 ± 3 mmHg) than in the upright (2 ± 3, 9 ± 3, and 17 ± 3 mmHg) position. During dynamic exercise,the increases in MAP evoked by 25, 50, and 75 mmHg LBPP were greater inthe supine (13 ± 2, 28 ± 3, and 40 ± 3 mmHg) than in theupright (7 ± 3, 12 ± 3, and 25 ± 3 mmHg)position. We conclude that the systemic pressure response to LBPP isclearly dependent on the body position, with the larger pressureresponses being associated with the supine position both at rest andduring dynamic leg exercise.

     

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.

     

Graded cutaneous vascular responses to dynamic leg exercise

The cutaneous vascular conductance-esophageal temperature (CVC-Tes) relationship was examined at five work loads (75-200 W) in each of four men to find whether there is a role for exercise intensity in the control of skin blood flow (SkBF). Several factors contributed to our evaluation of the CVC-Tes relationship during work. Laser-Doppler velocimetry (LDF) provided a continuous measure of SkBF that is not influenced by underlying muscle blood flow. Local warming to 39 degrees C at the site of measurement of SkBF provided a consistent skin temperature and facilitated observation of changes in LDF. Mean arterial pressure was measured noninvasively once per minute to calculate CVC. Supine exercise minimized baroreceptor-induced cutaneous vasoconstriction. Our major finding was that the internal temperature at which CVC began to rise during exercise (CVC threshold) was graded with work load beyond 125 W (P less than 0.05). In that range the CVC threshold increased by 0.16 degrees C for every increment of 25 W. The CVC threshold was never reached at the highest work load in three of the four subjects. There was no consistent effect of work load on the slope of the CVC-Tes relationship or on the internal temperature at which sweating began during exercise (sweat rate threshold). We conclude that the level of work beyond 125 W affects the CVC-Tes relationship in a graded fashion, principally through shifts in threshold.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.     

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.     

Effects of increased muscle perfusion pressure on responses to dynamic leg exercise in man

Ventilatory, cardiovascular and metabolic functions and work performance were studied in men performing incremental-load dynamic leg exercise until exhaustion. Part I: Responses to supine exercise were investigated in 8 subjects during exposure of the lower body to subatmospheric pressure at -6.67 kPa (-50 mm Hg) (Lower Body Negative Pressure, LBNP). Due to curtailment of stroke volume, cardiac output was reduced by LBNP over a wide range of work intensities, including heavy loads: ventilation, oxygen uptake and blood lactate concentrations increased with work load, but at lower rates than in the control condition. Part II: In 9 subjects, work performance was compared in three conditions: supine exercise with and without LBNP, and upright exercise. Performance in supine exercise was enhanced by LBNP, and was further improved in upright exercise. In supine exercise, the LBNP-induced reduction in blood lactate and enhancement of work performance are attributed to a more efficient muscle blood flow resulting from increased local perfusion pressure. This strongly suggests that the primary limitation of work performance was set by the peripheral circulation in working muscles rather than by cardiac performance. A similar mechanism may, in part, explain why work performance in dynamic leg exercise was greater in the upright than in the supine posture. It is also concluded that supine leg exercise during LBNP is a useful model of upright exercise, with regard to the central circulation and the circulation in working muscles.     

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.

     

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.     

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.     

Supine lower body negative pressure exercise during bed rest maintains upright exercise capacity.

Bed rest and spaceflight reduce exercise fitness. Supine lower body negative pressure (LBNP) treadmill exercise provides integrated cardiovascular and musculoskeletal stimulation similar to that imposed by upright exercise in Earth gravity. We hypothesized that 40 min of supine exercise per day in a LBNP chamber at 1.0-1.2 body wt (58 +/- 2 mmHg LBNP) maintains aerobic fitness and sprint speed during 15 days of 6 degrees head-down bed rest (simulated microgravity). Seven male subjects underwent two such bed-rest studies in random order: one as a control study (no exercise) and one with daily supine LBNP treadmill exercise. After controlled bed-rest, time to exhaustion during an upright treadmill exercise test decreased 10%, peak oxygen consumption during the test decreased 14%, and sprint speed decreased 16% (all P < 0.05). Supine LBNP exercise during bed rest maintained all the above variables at pre-bed-rest levels. Our findings support further evaluation of LBNP exercise as a countermeasure against long-term microgravity-induced deconditioning.     

间断下体负压暴露方式对下体负压耐力的影响

目的：探讨不同方式反复下体负压锻炼对下体负压耐力的影响,以期筛选最佳的负压锻炼方式。方法：27名男性健康受试者随机分成3组,分别进行－5.33kPa8min(A组）、6.67kPa4min（B组）、6.67kPa8min（C组）的下体负压锻炼后累积应激指数（CSI）、总耐受时间（DNP）较锻炼前显著提高,A、B组上述指标无显著变化,下体负压暴露时的心率较平静状态显著升高,收缩压显著降低,舒张压无显著变化。结论：经过－6.67kPa/d8min连续8d的间断下体负压可以显著提高下体负压耐力。     

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.     

Comparing cardiovascular responses during exercise between head-down tilt pedaling with lower body negative pressure and upright cycling in man

If lower body negative pressure (LBNP) loaded on exercise in weightlessness environment is able to derive a comparable cardiovascular responses to these in the ground, it should be identified as an optimal LBNP for exercise in space. To investigate the LBNP, 7 young subjects were exercised 4 work rates stepping up every 50 watts from 50 watts to 200 watts every 5 minutes in the upright position or 6 degree head down tilt position with each LBNP of 20, 40, 60, 80, and 100 mmHg. Oxygen uptake during tilt exercise with over 60 mmHg LBNP was not different from it in upright exercise. Heart rate and systolic arterial pressure responses to exercise were very similar between tilt exercise with 60 mmHg LBNP and upright exercise. In conclusion, the optimal LBNP loaded on exercise in space should be around 60 mmHg.     

Sympathetic nerve activity in arm and leg muscles during lower body negative pressure in humans

Nonhypotensive lower body negative pressure (LBNP) is reported to decrease forearm but not calf blood flow as measured by strain-gauge plethysmography. This suggests that unloading of cardiopulmonary receptors increases sympathetic outflow to arm but not to leg. To test this hypothesis we measured muscle sympathetic nerve activity (MSA) in the arm (radial nerve) and leg (peroneal nerve) simultaneously during LBNP. In eight healthy subjects, we measured heart rate, blood pressure, and radial and peroneal MSA during LBNP at 10 and 20 mmHg. There was no difference between radial and peroneal MSA at rest, and there were successive parallel increases of MSA in both nerves during LBNP at 10 and 20 mmHg. These data indicate that there are nearly identical increases of sympathetic outflow to the arm and leg during mild to moderate degrees of orthostatic stress.