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J Appl Physiol 95: 159-166, 2003; doi:10.1152/japplphysiol.01079.2002
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Augmentation of the push-pull effect by terminal aortic occlusion during head-down tilt

Amy L. Hakeman, Jami L. Shepard, and Don D. Sheriff

Department of Exercise Science, The University of Iowa, Iowa City, Iowa, 52242

Submitted 25 November 2002 ; accepted in final form 26 February 2003


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the "push-pull effect." The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90° head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90° head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 ± 1.3, -23 ± 0.7, and -28 ± 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences (P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.

arterial blood pressure; tilt; gravitational stress; orthostatic stress

RELATIVELY BRIEF EXPOSURE to <1 G along the long (z) axis of the body [e.g., microgravity, 0 vertical acceleration (Gz), or negative Gz] reduces Gz tolerance during subsequent exposure to positive Gz stress. This pattern of gravitational (G) stress occurs in the flying environment when a pilot first pushes on the control stick to unload the aircraft to zero or negative G, and then subsequently pulls on the control stick, thereby imposing high positive Gz stress. For this reason, the phenomenon of reduced Gz tolerance after brief exposure to hypogravity has been termed the "push-pull effect" (2). The reduction in Gz tolerance is associated with an exaggerated reduction in eye-level blood pressure (ELBP) in response to positive Gz (2, 9, 10, 14). The push-pull effect has been demonstrated in human subjects (1, 2, 4) as well as in both conscious (14) and anesthetized (9, 10, 14) rats. The axis of rotation appears to be an important factor in humans (4) but not in rats (9), and gender does not appear to be a factor in rats (9). The autonomic nervous system appears to play an important role in producing the push-pull effect inasmuch as inhibition of autonomic ganglionic neurotransmission eliminates the push-pull effect (10).

Although the mechanism(s) responsible for the push-pull effect are incompletely understood, it has been speculated that the arterial baroreflexes play a role (4, 6, 8–10, 14). The hypothesis is that the rise in carotid distending pressure imposed during the push activates the carotid sinus baroreceptors, which in turn slows the heart and initiates peripheral vasodilation in an effort to restore carotid pressure back toward its baseline value. These blood pressure-lowering responses, initiated during the push, persist during the early phase of the subsequent pull due to the phase lag inherent in the baroreflex arc (13). At this time, the mechanical reduction in carotid artery pressure produced by the sudden reversal in acceleration is added to the pressure-reducing effects of the baroreceptor-induced bradycardia and peripheral vasodilation. This can lead to an unexpectedly large fall in cerebral perfusion pressure and loss of consciousness in extreme conditions (12). Conversely, the vestibular-autonomic system also constitutes a potential mechanism (4), but one that presumably operates independent of hydrostatic pressure changes.

One purpose of the present study was to test the hypothesis that baroreceptor reflexes are an important mechanism involved in the push-pull effect. If the hypothesis that carotid hypertension is a mechanism that induces a push-pull effect were true, then augmenting the carotid hypertension during the push phase should cause a more profound fall in blood pressure during subsequent positive Gz stress by eliciting a larger initial depressor response due to the higher initial carotid hypertension. One approach to studying the push-pull effect has been to subject rats to push-pull G stress by tilting (9, 10, 14). In these studies, positive Gz stress was imposed by tilting the animals 90° head up. Push-pull G stress was imposed by tilting the animals 90° head down immediately before head-up tilt. A limitation to ground-based tilting is that simulated hypogravity is limited to -1 Gz. (i.e., 90° head-down tilt). This is a particular limitation in small animals, such as rats, that have a short heart-to-eye distance. For example, 90° head-down tilt in rats raises ELBP by ~5 mmHg (9, 10, 14), whereas in humans this maneuver raises ELBP by ~25 mmHg. In the present study, we sought to overcome this limitation. Inasmuch as bilateral thigh cuff inflation is a useful means of increasing upper body arterial pressure and thereby activating baroreceptor reflexes in human subjects (16), we devised experiments employing terminal aortic vascular occlusion as a means of augmenting the effects of head-down tilt.

Specifically, we hypothesized that augmenting the blood pressure changes ordinarily induced by head-down tilt by the combined application of terminal aortic occlusion and head-down tilt would increase the magnitude of the push-pull effect as a test of the idea that baroreceptors are an important mechanism involved in this phenomenon. We also sought to shed light on the potential role of the vestibular-autonomic system in push-pull G stress. The approach here was to inflate the occluder cuff when the animal was supine before head-up tilt to test whether simulating head-down tilt with cuff inflation would produce a push-pull effect. Is head-down rotation and the associated vestibular stimulation obligatory for expression of a push-pull effect? A third purpose of this study was to determine the effect on ELBP during push-pull G stress of simulating the effects that G suit inflation exerts on vascular resistance. The occluder cuff surrounding the terminal aorta and vena cava was inflated during head-up tilt to increase vascular resistance and thereby increase Gz tolerance.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
The following procedures meet National Institutes of Health guidelines and were reviewed and approved by the Institutional Animal Care and Use Committee of The University of Iowa.

Surgical Preparation

Eighteen male and female Sprague-Dawley rats (274–413 g) were anesthetized with isoflurane and restrained supine on a homeothermically controlled surgical tilt table. The animal's body temperature was maintained at 37°C. Over ~60–90 min, a catheter was implanted in the right carotid artery in all animals and in the left femoral artery in six of the animals. A pneumatic vascular occluder cuff was implanted around the terminal aorta and inferior vena cava in all animals. The wounds were closed, and the protocols were begun within ~10 min.

Experimental Procedures

For all rotations, the tilt table was oriented such that Earth's gravity vector was applied across the animal's y-axis so that Gz stress could be imposed by manually rotating the table and thus the animal ±90° about the animal's x-axis (roll rotation). The starting position was 0 Gz. The control treatment consisted of rotating the animal 90° head up (+1 Gz) for 10 s. The push-pull treatment consisted of 10 s of head-up tilt that was immediately preceded by 2 s of 90° head-down tilt (-1 Gz). Movement times were ~0.5 s (2–4 g/s). Specific protocols are described below. The animal recovered for at least 90 s in the horizontal (0 Gz) position between tilts.

Augmented push-pull. The primary aim here was to increase the carotid hypertension during the push phase of a push-pull G profile. This protocol consisted of control and push-pull treatments and an augmented push-pull treatment achieved by full inflation of the occluder cuff during 2 s of head-down tilt. The cuff was rapidly inflated so that the vena cava and the aorta would be compressed in rapid succession to minimize blood volume from accumulating and being trapped distal to the cuff. The 16 animals used for this protocol were subjected to six G profiles in a counterbalanced design to minimize possible time effects of repeated exposure to G stress. See Fig. 1 for a schematic illustration of the experimental protocol. In six of the rats, 2 s of cuff inflation in isolation (no tilt) were imposed between the push-pull and the augmented push-pull trials in both the ascending and descending order.



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  		Fig. 1. Schematic illustration of gravitational (G) profiles in the augmented push-pull protocol. Sequence repeated in reverse order. Shaded oval indicates 2 s of terminal aortic and vena caval cuff inflation during negative vertical acceleration (Gz) G stress.

 

Simulated push-pull. The aim here was to mimic the hydrostatic pressure changes normally induced by head-down tilt by vascular occlusion alone. This protocol consisted of control and push-pull treatments and a simulated push-pull treatment that consisted of 10 s of head-up tilt immediately preceded by 2 s of vascular occlusion while the animal was supine. The 13 animals used for this protocol were subjected to six G profiles in a counterbalanced design, as illustrated in Fig. 2. In six of the rats, cuff inflation alone for 2 s was imposed between the push-pull and the simulated push-pull trials in both the ascending and descending order.



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  		Fig. 2. Schematic illustration of G profiles in the simulated push-pull protocol. Sequence repeated in reverse order. Shaded oval indicates 2 s of terminal aortic and vena caval cuff inflation applied to simulate the hydrostatic pressure changes normally produced by negative Gz stress.

 

Cuff only. To verify that cuff inflation had the intended effect of inducing reflex responses via upper body hypertension, 2 s of cuff inflation alone (no tilt) was imposed in seven rats before and after administration of hexamethonium (10 mg/kg) to inhibit autonomic ganglionic neurotransmission.

Simulated G suit. The aim here was to simulate the effects of a G suit by imposing aortic vascular occlusion during head-up tilt. This protocol consisted of control and push-pull G stress imposed with and without cuff inflation during head-up tilt. The 16 animals used for this protocol were subjected to eight G profiles in a counterbalanced design, as illustrated in Fig. 3.



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  		Fig. 3. Schematic illustration of G profiles in the simulated G suit protocol. Sequence repeated in reverse order. Shaded ovals indicate 10 s of terminal aortic and vena caval cuff inflation applied to simulate the resistance-raising effect of G suit inflation.

 

Data Collection

The carotid artery catheter was connected to a pressure transducer (PE10 EZ, Ohmeda, Madison, WI) secured at eye level. The femoral arterial catheter was connected to a similar transducer mounted at mid-thigh level.

Signals were digitized at 1 kHz and stored on the fixed disk of a laboratory microcomputer for subsequent analysis (PONEMAH Physiology Platform, P3, Gould Instruments, Valley View, OH).

Data Analysis

Data analysis was performed on 1-s averages of the digitized data. Baseline ELBP was established by calculating the average pressure over the 5 s immediately preceding tilt onset. The magnitude of the response of ELBP to negative Gz stress and to cuff inflation alone ({Delta}Push) was calculated as the difference between pressure observed 1 s before the transition from -1 Gz to +1 Gz (or immediately before cuff deflation) and baseline pressure. The magnitude of the response of ELBP to the positive Gz stress ({Delta}Pull) was calculated as the difference between baseline pressure and the nadir pressure observed after the onset of head-up tilt (or cuff deflation). Data from the multiple trials under each condition within each rat were averaged together such that each rat only contributed once to the group mean data and to the statistical analysis.

Statistical Analysis

For the augmented push-pull and simulated push-pull protocols, the baseline, {Delta}Push, and {Delta}Pull values of ELBP were analyzed statistically by repeated-measures ANOVA (7). Adjustment for multiple simultaneous comparisons was done by the Bonferroni procedure. Baseline, {Delta}Push, and {Delta}Pull values of ELBP from the trials in which the cuff was inflated in isolation before hexamethonium were compared by paired t-tests to the respective values from the trials in which the cuff was inflated in isolation after hexamethonium. Also, for the trials in which the cuff was inflated in isolation, a single sample t-test was used to test whether the {Delta}Pull value of ELBP after hexamethonium was significantly different from zero. Adjustment for multiple simultaneous comparisons was done by the Bonferroni procedure. For the simulated G suit trials, the baseline, {Delta}Push, and {Delta}Pull values of ELBP from the control trials with no cuff inflation were compared by paired t-tests to the respective values from the push-pull trials with no cuff inflation. Likewise, the baseline, {Delta}Push, and {Delta}Pull values from the control trials with cuff inflation were compared by paired t-tests to the respective values from the push-pull trials with cuff inflation. Finally, the baseline, {Delta}Push, and {Delta}Pull values of ELBP from the trials with no cuff inflation (control and push-pull combined) were compared by paired t-tests to the respective values from the trials with cuff inflation (control and push-pull combined). A P value of <0.05 was selected to indicate statistical significance. Data are reported as means ± SE.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Augmented Push-Pull

Group mean responses of ELBP and femoral arterial pressure from the control, push-pull, and augmented push-pull trials are shown in Fig. 4. Baseline ELBP, {Delta}Push, and {Delta}Pull along with femoral pressure are presented in Table 1. The values of {Delta}Push from both the push-pull (P < 0.001) and the augmented push-pull (P < 0.001) trials were significantly greater than the value of {Delta}Push from the control trials. Also, the value of {Delta}Push from the augmented push-pull trials was significantly greater than the value of {Delta}Push from the push-pull trials (P < 0.001). The {Delta}Pull values exhibited the same pattern. The values of {Delta}Pull from the push-pull (P < 0.01) and the augmented push-pull (P < 0.001) trials were significantly greater than the value of {Delta}Pull from the control trials. Also, the value of {Delta}Pull from the augmented push-pull trials was significantly greater than the value of {Delta}Pull from the push-pull trials (P < 0.001). Head-down tilt caused directionally opposite changes in ELBP and femoral arterial pressure. Cuff inflation caused an exaggerated fall in femoral arterial pressure.



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  		Fig. 4. Group mean responses of eye-level blood pressure (A) and femoral arterial pressure (B) during control positive Gz stress (Con; thick solid line), push-pull G stress (PP; thin solid line), and augmented push-pull G stress (Aug PP; dashed line). Cuff inflation imposed during head-down tilt augments the magnitude of the push-pull effect. Values are means ± SE.

 

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  		Table 1. Blood pressure responses to control, push-pull, and augmented push-pull gravitational stress

 

Simulated Push-Pull

Figure 5 shows representative data from one rat in response to push-pull G stress and simulated push-pull treatment. Head-down tilt raised ELBP, which subsequently fell during head-up tilt. Likewise, cuff inflation raised ELBP, which subsequently fell during head-up tilt. Group mean responses of ELBP and femoral arterial pressure for control, push-pull, and simulated push-pull treatments are shown in Fig. 6. Baseline ELBP, {Delta}Push, and {Delta}Pull values along with femoral pressure are presented in Table 2. The values of {Delta}Push from both the push-pull (P < 0.001) and the simulated push-pull (P < 0.001) trials were significantly greater than the value of {Delta}Push from the control trials. The value of {Delta}Push from the simulated push-pull trials was significantly less than the value of {Delta}Push from the push-pull trials (P < 0.05). The values of {Delta}Pull from both the push-pull trials (P < 0.05) and the simulated push-pull trials (P < 0.001) were significantly greater than the value of {Delta}Pull from the control trials. Also, the value of {Delta}Pull from the simulated push-pull trials was significantly greater than the value of {Delta}Pull from the push-pull trials (P < 0.01). Head-down tilt caused directionally opposite changes in ELBP and femoral arterial pressure. Cuff inflation caused an exaggerated fall in femoral arterial pressure.



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  		Fig. 5. Response of eye-level blood pressure to push-pull Gz stress imposed by tilt (A) and to simulated push-pull G stress imposed by cuff inflation followed by head-up tilt (D) in an anesthetized rat. The response of femoral arterial pressure to push-pull (B) and simulated push-pull (E) G stress is also shown. The degree of tilt during push-pull (C) and simulated push-pull (F) are shown schematically. Shaded oval denotes 2 s of cuff inflation.

 


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  		Fig. 6. Group mean responses of eye-level blood pressure (A) and femoral arterial pressure (B) during control +Gz stress (Con; thick solid line), push-pull G stress (PP; thin solid line), and simulated push-pull G stress (Sim PP; dashed line). Cuff inflation alone produces a push-pull effect. Values are means ± SE.

 

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  		Table 2. Blood pressure responses to control, push-pull, and simulated push-pull gravitational stress

 

Cuff Only

The response of ELBP to 2 s of cuff inflation alone (no tilt) before and after hexamethonium as a percentage of baseline pressure is shown in Fig. 7. Hexamethonium reduced baseline pressure from 104 ± 3.4 to 94 ± 3.2 mmHg (P < 0.05). Hexamethonium increased the value of {Delta}Push from 4 ± 0.7 to 7 ± 0.8 mmHg (P < 0.05). Hexamethonium reduced the value of {Delta}Pull from -7 ± 1.3 to -3 ± 0.5 mmHg (P < 0.05). The value of {Delta}Pull after hexamethonium (-3 mmHg) was significantly different from zero (P < 0.05).



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  		Fig. 7. Response of eye-level blood pressure to brief (2 s) terminal aortic and vena caval occlusion. Occlusion raises eye-level blood pressure, and cuff deflation induces hypotension. After hexamethonium (post-Hex), eye-level blood pressure rises further during cuff inflation and decreases less after cuff deflation. Pre-Hex, before hexamethonium.

 

Simulated G suit

The group mean response of ELBP and femoral arterial pressure for the control with no cuff inflation, push-pull with no cuff inflation, control with cuff inflation (simulated G suit), and push-pull with cuff inflation (simulated G suit) trials are shown in Fig. 8. Baseline ELBP, {Delta}Push, and {Delta}Pull values along with femoral pressure are presented in Table 3. The value of {Delta}Push from the push-pull trials with no cuff inflation was significantly greater (P < 0.001) than the value of {Delta}Push from the control trials with no cuff inflation. Likewise, the value of {Delta}Push from the push-pull trials with cuff inflation was significantly greater (P < 0.001) than the value of {Delta}Push from the control trials with cuff inflation. The value of {Delta}Push from the trials with no cuff inflation (control and push-pull combined; 4 ± 0.7 mmHg) was no different (P = 0.48) than the {Delta}Push value from the trials with cuff inflation (control and push-pull combined; 4 ± 0.7 mmHg). The value of {Delta}Pull from the push-pull trials with no cuff inflation was significantly greater (P < 0.05) than the value of {Delta}Pull from the control trials with no cuff inflation trials. The value of {Delta}Pull from the push-pull trials with cuff inflation and the value of {Delta}Pull from the control trials with cuff inflation were not different (P = 0.68). The value of {Delta}Pull from all trials with cuff inflation (control and push-pull combined; -17 ± 1.2 mmHg) was significantly less (P < 0.001) than the value of {Delta}Pull from all trials with no cuff inflation (control and push-pull combined; -22 ± 1.0 mmHg).



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  		Fig. 8. Group mean responses of eye-level blood pressure (A) and femoral arterial pressure (B) during control positive Gz stress (Con; thick solid line), push-pull G stress (PP; thin solid line), control positive Gz stress with aortic cuff inflation (Cuff+; simulated G suit; thick dashed line), and push-pull G stress with cuff inflation (Cuff+; simulated G suit; thin dashed line). Trials were done with cuff inflated (Cuff+) or with cuff not inflated (Cuff-). Cuff inflation during head-up tilt supports eye-level blood pressure and eliminates the push-pull effect. Values are means ± SE.

 

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  		Table 3. Blood pressure responses to control and push-pull gravitational stress with and without aortic cuff inflation (simulated G suit)

 


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
The major new findings of this study are as follows. Augmentation of head-down tilt with terminal aortic and inferior vena caval occlusion causes ELBP to increase to a greater extent during the push phase, and this augmentation leads to a greater fall in ELBP during subsequent head-up tilt. A push-pull effect can be elicited in anesthetized rats when negative Gz stress is simulated with abdominal vascular occlusion, i.e., actual rotation to the head-down position is not obligatory for expression of a push-pull effect. Cuff inflation alone produces carotid hypertension, which induces a baroreflex depressor response. Cuff deflation induces system hypotension, and this hypotension is reduced but not eliminated by inhibition of autonomic ganglionic neurotransmission with hexamethonium. Use of terminal aortic and inferior vena caval occlusion during head-up tilt to simulate a G suit reduces the fall in ELBP induced by head-up tilt and eliminates the push-pull effect.

The influence on the push-pull effect of altering the duration of exposure to simulated hypogravity has been examined in a number of studies with mixed results. Banks et al. (1) found that increasing the duration of exposure to -2 Gz resulted in a progressive fall in mean blood pressure during subsequent exposure to +2.25 Gz imposed by centrifugation of human subjects. In contrast, Cheung et al. (4) found that increasing the duration of exposure to -0.71 Gz led to lesser reductions in blood pressure during subsequent exposure to +0.96 Gz imposed by tilting human subjects. Finally, Sheriff et al. (14) showed that increasing head-down dwell time from 0.5 to 9 s had no effect on the magnitude of the push-pull effect in anesthetized rats. To our knowledge, no study has evaluated the effects of altering the magnitude of simulated hypogravity on the push-pull effect.

Limb vascular occlusion has been used by a number of investigators to explore cardiovascular regulatory mechanisms. Occlusion has been used to study the effects of reducing downstream pressure and blood flow as well as to study the effects of increasing pressure above the site of occlusion. Acute compression of the arterial supply of the lower limbs has been used to study vascular control mechanisms in limbs (3) as well as to elicit reflexes from active tissues during exercise (15). Alternatively, limb vascular occlusion has been used to study baroreceptor reflex responses to the increase in upper body arterial pressure evoked by this intervention (16). This was the primary reason we employed terminal aortic occlusion in the augmented push-pull and simulated push-pull experiments. It is unlikely that the very brief (2 s) occlusions imposed in the present study evoked metabolic vasodilation. For example, metabolic vasodilation does not occur in resting limbs when blood flow and perfusion pressure are reduced in graded steps for 8–10 min (3). It is possible that brief terminal aortic occlusion may have elicited myogenic vasodilation inasmuch as myogenic vasodilator responses have been reported to occur within this time frame (5). However, myogenic vasomotor responses are unlikely in the rat given the small changes in femoral pressure (in the absence of vascular occlusion) during tilt, owing to their relatively small size. Conversely, myogenic vasomotor responses are far more likely in humans because the pressure changes are much larger, owing to their relatively large size. Moreover, when isolated arterioles expressing myogenic tone are suddenly unloaded (as would occur in human legs during head-down tilt), they initially recoil to smaller diameters and then contract to even smaller diameters before eventually exhibiting myogenic relaxation (5). The extent to which arteriolar diameter would increase if the distending pressure was suddenly restored to baseline levels or higher (as would occur in human legs when positive Gz stress follows negative Gz stress) under these conditions is unknown. Nevertheless, if hindlimb myogenic vasodilation were to occur, it could also contribute to the push-pull effect.

Augmented Push-Pull

Our results support the hypothesis that the baroreceptors are involved in producing the push-pull effect. We found that increasing the magnitude of the stimulus to the carotid baroreceptors was associated with an increase in the magnitude of push-pull effect. The rationale for our approach was that vascular occlusion would increase total peripheral resistance and thereby raise blood pressure proximal to the occluder cuff. This should add to the increase in ELBP induced by the hydrostatic effects of head-down tilt, and indeed this is what we observed, i.e., ELBP rose by 12 mmHg with the combination of head-down tilt and vascular occlusion, whereas ELBP rose by only 8 mmHg during head-down tilt alone. Cuff inflation also augmented the fall in lower body pressure that accompanies negative Gz stress, which also constitutes a potential stimulus for inducing a push-pull effect via myogenic vasomotor responses. Augmentation of these stimuli increased the magnitude of the push-pull effect (Fig. 4; Table 1). The response of upper body arterial pressure to brief occlusion alone (no tilt) provides further support of the importance of the arterial baroreceptor reflexes in producing the push-pull effect. Cuff inflation alone raised arterial pressure, and cuff deflation induced hypotension. Importantly, hexamethonium increased the magnitude of the hypertension induced by cuff inflation, which indicates that the baroreceptors in fact elicit a depressor response to this stimulus. The observation that blood pressure fell less from baseline after cuff deflation after hexamethonium indicates that this depressor response contributed to the cuff deflation-induced fall in pressure when autonomic function was intact. To our knowledge, our study constitutes the first evaluation of the influence of altering the magnitude of simulated hypogravity on the push-pull effect, and the observed augmentation of the push-pull effect associated with augmented carotid hypertension induced by cuff inflation implicates the baroreflexes.

Simulated Push-Pull

The vestibular system has been shown to exert effects through the autonomic nervous system (11, 17) and has been implicated as a factor that can modulate the magnitude of the push-pull effect (4). In the simulated push-pull protocol, we sought to evaluate the overall importance of vestibular-autonomic regulatory mechanisms in producing the push-pull effect. Our approach was to impose the changes in regional blood pressure ordinarily elicited by negative Gz stress without the stimulation of the vestibular system that ordinarily results from altering the animal's orientation to gravity. If the vestibular system played a crucial role in producing the push-pull effect, our simulated push-pull protocol would not be expected to elicit an exaggerated reduction in ELBP during subsequent positive Gz stress. In contrast, we found that simulating the hydrostatic consequences of head-down tilt by cuff inflation produced a push-pull effect. In fact, as shown in Table 2, the magnitude of push-pull effect observed in the simulated push-pull trials (5 mmHg below ELBP during control Gz stress) was greater than was observed during the push-pull trials (2 mmHg below ELBP during control Gz stress). Across all experiments, the magnitude of {Delta}Pull observed during the simulated push-pull trials was exceeded only by the {Delta}Pull observed during the augmented push-pull trials. Thus, although the vestibular system can modulate the push-pull effect (4), actual rotation is not obligatory for expression of a push-pull effect. Overall, our results argue against a potent role for the vestibular-autonomic system in producing the push-pull effect in anesthetized rats subjected to tilting.

Simulated G suit

As expected, we found that an increase in vascular resistance imposed during head-up tilt attenuated the fall in ELBP that accompanies G stress. Cuff inflation during head-up tilt also eliminated the push-pull effect. Thus a more aggressive G suit pressurization schedule when positive Gz stress follows exposure to hypogravity may help protect pilots against the push-pull effect. The finding that hydraulic isolation of the hindbody during head-up tilt (simulated G suit) eliminated the push-pull effect points to the importance of changes in this region in producing this effect.

Relative Importance of Upper Body Hypertension Vs. Lower Body Hypotension

Compared with head-down tilt, cuff inflation alone produced a smaller rise in ELBP and an exaggerated fall in femoral arterial pressure. Thus this approach to simulating negative Gz stress likely provided a smaller-than-desired stimulation of baroreceptors and a larger-than-desired stimulation for myogenic vasodilation downstream from the cuff. Interestingly, the simulated push treatment lowered ELBP during subsequent positive Gz stress more so than did head-down tilt alone. Thus it appears that lower body hypotension of sufficient magnitude may contribute importantly to the push-pull effect. The observation that hypotension after isolated cuff inflation persisted after autonomic blockade (Fig. 7) indicates that a nonautonomic mechanism(s) causes hypotension and thus may contribute to the hypotension seen when autonomic function is intact. The nonautonomic hypotension could stem from myogenic relaxation, arterial refilling, or venous refilling. Clearly this is an underappreciated factor in light of the preponderance of attention given to baroreceptor-mediated mechanisms in previous investigations (4, 6, 8–10, 14).

Potential Limitations

Experiments were carried out in anesthetized rats so that our results would not be complicated by the cardiovascular consequences associated with excitement and/or muscular straining associated with tilting. Importantly, autonomic reflex function remains intact (although possibly attenuated compared with the conscious state) under isoflurane anesthesia, as evidenced by the partial restoration of arterial pressure during the 10 s of head-up tilt (Figs. 4, 5, 6, 8). This restoration is not seen under ketamine anesthesia nor under isoflurane anesthesia after hexamethonium (10).

In summary, simulation of an increase in the magnitude of negative Gz stress by abdominal vascular occlusion during head-down tilt increases the magnitude of the push-pull effect in anesthetized rats as assessed by ELBP. Push-pull G stress can be simulated by hindbody vascular occlusion in the absence of head-down tilt. Both the augmented and simulated push-pull effects are mediated in part by baroreceptor reflexes. Hindbody vascular occlusion (simulated G suit) during head-up tilt eliminates the push-pull effect.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
This work was supported by National Heart, Lung, and Blood Institute Grant HL-46314.


   FOOTNOTES
 

Address for reprint requests and other correspondence: D. D. Sheriff, Exercise Science, 518 Field House, Iowa City, IA 52242.

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

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