J Appl Physiol 99: 2144-2148, 2005.
First published August 4, 2005; doi:10.1152/japplphysiol.00336.2005
8750-7587/05 $8.00
Regional difference of blood flow in anesthetized rats during reduced gravity induced by parabolic flight
Kunihiko Tanaka,
Taro M. Gotoh,
Chihiro Awazu, and
Hironobu Morita
Department of Physiology, Graduate School of Medicine, Gifu University, Gifu, Japan
Submitted 23 March 2005
; accepted in final form 28 July 2005
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ABSTRACT
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To examine a hypothesis that change in regional blood flow due to decreased hydrostatic pressure gradient and redistribution of blood during reduced gravity (rG) is different between organs, changes in cerebrocortical blood flow (CBF) and blood flow in the temporal muscle (MBF) with exposure to rG were measured in anesthetized rats in head-up tilt and flat positions during parabolic flight. Carotid arterial pressure (CAP), jugular venous pressure (JVP), and abdominal aortic pressure were also measured simultaneously. In the head-up tilt group, CBF increased by 15 ± 3% within 3 s of entry into rG and rapidly recovered during rG. MBF also increased, but the change was significantly greater than that of CBF. JVP increased by 1.8 ± 0.5 mmHg, probably due to loss of hydrostatic pressure gradient, since the measuring point of JVP was 2–3 cm above the hydrostatic indifference point. CAP and abdominal aortic pressure increased by 16.7 ± 2 and 7.7 ± 2 mmHg, respectively, compared with the 1-G condition. Muscle vascular resistance [(CAP – JVP)/MBF] decreased on entry into rG, but no significant change was observed in cerebrocortical vascular resistance [(CAP – JVP)/CBF]. In the flat group, no significant change was observed in all the variables. The results indicate that arteriolar vasodilatation occurs in the temporal muscle but not in the cerebral cortex. Thus the blood flow control mechanism at the onset of rG is different between intra- and extracranial organs.
cerebral blood flow; cerebral perfusion pressure; muscle blood flow; carotid arterial pressure; head-up tilt
EXPOSURE OF A HUMAN BODY to reduced gravity (rG) results in a disappearance of the gravitational fluid-pressure gradient and a cephalad fluid shift (21). This shift might cause various symptoms such as facial puffiness, nasal congestion, and decrease in leg volume in the space (13, 14). During simulated rG with head-down tilt or bed rest in humans, the cutaneous blood flow in the forehead and cheek, which is perfused by the external carotid artery, increases (1, 20).
Recently, we have measured acute responses of cerebral hemodynamics with exposure to rG in rats. Cerebral perfusion pressure increases in rats in the head-up tilt (HUT) position during rG induced by a free drop but does not change in rats in the horizontal position (2, 3). The increase is caused by a larger increase in carotid arterial pressure (CAP) than that in the jugular venous pressure (JVP). Despite the increase in CAP, the flow velocity in the internal carotid artery does not change significantly (2); this maintenance of flow velocity is considered a result of cerebral vasoconstriction (2, 12, 17). However, the capillary blood flow velocity and the diameters of vessels in the iris, which is also perfused by the internal carotid artery, are significantly increased by 33 and 9%, respectively, based on the increase in cerebral perfusion pressure (3). The blood flow velocity in the internal carotid artery reflects the cerebral blood flow rather than the ophthalmic artery (11, 21, 27). On the basis of these results, we hypothesize that the local blood flow response due to change in hydrostatic pressure is different between tissues or organs despite the same height during exposure to rG. To examine this hypothesis, we simultaneously measured the cerebrocortical blood flow (CBF) and muscle blood flow (MBF) at the same height by using the same method during exposure to actual rG.
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METHODS
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Male Sprague-Dawley rats (n = 10) weighing 320–360 g (10–12 wk old) were used and maintained in accordance with the Guiding Principles for Care and Use of Animals in the Field of Physiological Science of the Physiological Society of Japan. The Animal Research Committee of Gifu University approved the experimental protocol.
Five to eight days before parabolic flight study, the first surgical intervention was performed. The rats were anesthetized with pentobarbital sodium (50 mg/kg ip) and placed in a stereotaxic apparatus (Summit Medical, Tokyo, Japan). To measure CBF, a guide cannula for a laser Doppler flow probe was inserted. A hole of 
1-mm diameter was drilled through the interparietal bone (3.5 mm left to the midline and 1.3 mm caudal to the frontal suture), and the guide cannula was inserted into the cerebral cortex to a depth of 3 mm. The bone and the cannula were fixed with dental cement, and no bleeding was observed. On the day of the experiment, the rats were anesthetized with urethane and 
-chloralose (450 and 50 mg/kg ip, respectively). Through a midcervical incision, tracheotomy and intubation were performed. To measure CAP, a polyethylene catheter (PE-50, Becton Dickinson, Sparks, MD) was inserted into the right common carotid artery via the external carotid artery. The tip of the catheter was placed at the bifurcation to the internal carotid artery. To measure aortic pressure (AoP), a second catheter was inserted into the jugular vein via a small branch. A third catheter was also inserted into the abdominal aorta via the left femoral artery to measure AoP. Thus catheter tips for CAP and AoP were above hydrostatic indifference point (HIP), and the tip for the aorta was below HIP (23). All catheters were exteriorized and connected to pressure transducers (MP5200, Baxter, Deerfield, IL), each of which was fixed at the same level as the tip of the corresponding catheter to avoid gravitational pressure difference (4). The signals from the transducers were transmitted to amplifiers (AP-621G, Nihon Kohden, Tokyo, Japan). A laser Doppler flow probe was inserted into the cerebral cortex via the guide cannula described above (n = 10), and a second flow probe was inserted into the left temporal muscle at eye level to measure MBF (n = 6). The probes were connected to a flowmeter (FLO-N1, Omega Wave, Tokyo, Japan), and regional blood flows were simultaneously and continuously measured. For later analysis, these signals and the gravity level were recorded using a digital audiotape data recorder (RD-145T, TEAC, Tokyo, Japan) and an analog-to-digital converter with a data-acquisition program at a rate of 100 Hz (PowerLab, AD Instruments, New South Wales, Australia)
The rats were fixed in the prone position and placed in the 30° whole body HUT position (n = 10) or the flat position (n = 10). Their skulls were fixed using a stereotaxic apparatus. All rats were examined in both HUT and flat positions, but the order of positions was randomized.
After the stability of all the variables was ascertained, rG was acquired. In the present study, gravity was reduced from a horizontal flight. Thus the gravity condition directly changed from 1.1–1.2 G to rG, and the rG condition was continued for 12–13 s. The duration of rG was shorter than a usual parabolic flight maneuver; however, preceding hypergravity could be avoided. Between each parabolic flight, all variables were returned to the control value.
The data pertaining to gravity level, CAP, JVP, AoP, CBF, and MBF were averaged every 1 s. Data from 10 s of 1 G and 12 s from starting rG were analyzed. Time point that gravity reached to 0.9 G was considered starting rG. All data were expressed as means ± SE. CAP, JVP, and AoP were expressed as difference from averaged values during 10 s of 1 G. In the case of CBF and MBF, the averaged values during 10 s at the 1-G condition were considered as 100%, and the percent changes during rG were calculated. CAP – JVP was considered as perfusion pressure of the head region. Cerebrovascular resistance [(CAP – JVP)/CBF] (9) and vascular resistance in the temporal muscle [(CAP – JVP)/MBF] were also analyzed. Heart rate was calculated from waveform of CAP. For statistical analysis, a repeated-measures two-way analysis of variance was performed with time and groups as factors. The Bonferroni/Dunn post hoc test was employed for comparison of means within a group and between groups. Significance level was set at P < 0.05/number of comparisons.
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RESULTS
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The variables during the 1-G condition are summarized in Table 1. No significant difference was observed in all variables between the HUT and flat positions. Figure 1 shows the representative responses of gravity level, JVP, CAP, AoP, CBF, and MBF for HUT and flat positions before and during parabolic flight in the same rat. The gravity level transited from 1.1 to 0.04 G in 2 s, and the condition lasted through the measurement. In the HUT position, mean JVP changed from –1.3 to 0.6 mmHg by rG. This change was considered as a result of loss of hydrostatic pressure gradient. With rG, mean CAP also increased promptly from 138 to 169 mmHg. These changes were large when compared with those in JVP. Mean AoP also showed a simultaneous increase from 149 to 164 mmHg. CBF also slightly increased, but the change was small when compared with that in MBF. In the flat position, CVP, CAP, AoP, CBF, and MBF did not show any obvious change with rG.
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Table 1. Averaged values for jugular venous pressure, carotid arterial pressure, aortic pressure, cerebrocortical blood flow, and muscle blood flow in the temporal muscle during 1-G condition
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Fig. 1. Representative change in gravity (G) with a parabolic flight and responses of jugular venous pressure (JVP), carotid arterial pressure (CAP), aortic pressure (AoP), cerebrocortical blood flow (CBF), and muscle blood flow in the temporal muscle (MBF) in the same rat with head-up tilt (HUT; top) and flat (bottom) positions.
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Figure 2 shows the summarized data for gravity level and the changes in JVP, CAP, AoP, CBF, and MBF in the HUT and flat groups. The gravity level decreased to 0.06 ± 0.01 G at 2 s after the entry of the rG. AoP increased by 1.8 ± 0.5 mmHg at 3 s after the entry into rG, and the value was maintained throughout the rG condition. On entry into rG condition, CAP in the HUT group increased by 16.7 ± 2 mmHg and gradually decreased. AoP also increased significantly, but the change was significantly smaller than that of CAP. On entry into the rG condition, MBF increased by 81 ± 21% and gradually decreased. CBF also significantly increased by 15 ± 3% at 3 s after entry into rG, and the change was significantly smaller than that in MBF. Heart rate did not change significantly through the measurement (from 395 ± 14 to 393 ± 14 beats/min in the HUT group and 395 ± 16 to 395 ± 16 beats/min in the flat group).
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Fig. 2. Summarized values for variables during 1-G and reduced gravity (rG) condition. A: gravity (n = 10). B: changes in JVP (n = 10). C: changes in CAP and AoP (n = 10). D: changes in local CBF (n = 10) and MBF (n = 6). All variables were measured in both HUT and flat positions.
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Figure 3 shows the changes in the cerebral perfusion pressure calculated from CAP and JVP and relative changes in the regional vascular resistance calculated from the perfusion pressure and regional blood flow in the HUT and flat groups. The perfusion pressure in the HUT group during the rG condition significantly increased because the changes in CAP were greater than those in AoP. The perfusion pressure in the flat group did not change significantly because both CAP and JVP did not change despite the change in gravity. The vascular resistance in the cerebral cortex of both HUT and flat groups did not change significantly during the rG condition. However, the vascular resistance in the temporal muscle in the HUT group decreased on entry into rG. The resistance did not change significantly in the flat position.
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Fig. 3. Top: changes in perfusion pressure for the head region (n = 10). Bottom: local vascular resistance for cerebral cortex (CBF; n = 10) and temporal muscle (MBF; n = 6). All variables were measured with HUT and flat positions.
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DISCUSSION
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The following are the major findings of the present study. First, we clarify that MBF rapidly increases by 80% after entry into rG, and the local vascular resistance is significantly decreased when compared with that in the 1-G condition. On the other hand, CBF increases according to the increase in the perfusion pressure of the cephalic region on entry into rG, and the cerebral vascular resistance is maintained with rG exposure in HUT group. Second, the change in CAP on entry into rG is significantly greater than that in AoP. Third, these changes are not observed in the flat group.
Local blood flow is determined by perfusion pressure and vascular resistance (28). In the present study, the perfusion pressure in the cephalic region was increased on exposure to rG. MBF increased significantly, and the calculated vascular resistance was significantly smaller than that in the 1-G condition. In other words, on entry into rG, the diameter of the arterioles in the temporal muscle was larger than that of the 1-G condition because the vascular resistance is dominated by the diameter of blood vessels within a few seconds under physiological conditions (9). With this arteriolar dilatation, a larger number of capillaries are open and perfused (18). An increase in perfusion pressure not only increases the driving force required for perfusion but also leads to passive dilatation of the capillary bed within a second (7). The anatomical reason that muscles on the head are not restricted by the hard skull might help to lower the vascular resistance (19). Furthermore, the decrease in sympathetic nerve activity, which is observed during rG (10, 16), and the release of nitric oxide induced by increased flow (8, 18) might be also involved for the vasodilatation in the temporal muscle.
On the other hand, on entry into rG, the increase in CBF is significantly smaller than that of MBF. The calculated cerebrocortical vascular resistance was not significantly different from that in the 1-G condition since both CBF and perfusion pressure increased 15%. Thus the increase in CBF can be explained by increase in perfusion pressure. It is well known that CBF is fairly independent of perfusion pressure on account of autoregulation (12, 17, 22). However, the function is not accomplished within this short period since autoregulation of CBF is observed after 1 min of change in the cerebral perfusion pressure in rats (6). A different mechanism should dominate under a longer exposure to rG since relatively longer or chronic cephalad fluid shift causes cerebral vasoconstriction and lower cerebral blood flow (25, 26)
CAP increases on entry into rG, and the change is significantly higher than that of AoP and JVP. With exposure to rG, the hydrostatic pressure gradient in the blood vessel disappeared (23). Above HIP, hydrostatic pressure increases, and below HIP hydrostatic pressure decreases compared with those in the 1-G condition (23) Measuring points for CAP and JVP were higher than HIP, but that of AoP was lower than HIP in the HUT group. Height of HIP in rats is unclear, but it might be close to the heart level like in humans; the averaged change in JVP of 1.8 mmHg (2.3 cmH2O) in the present study is reasonable for consideration of the height difference between the HIP and measuring point (3). Of the 16.7-mmHg increase in CAP, 1.8 mmHg is caused by the loss of gravitational hydrostatic pressure gradient as observed in JVP. The other 14.9-mmHg change might be derived from a momentary increase in cardiac output. The loss of hydrostatic pressure gradient might facilitate venous return and increases cardiac output. Furthermore, a decrease in the intrathoracic pressure on exposure to rG increases the transmural pressure and diameter of the aorta (15) and the heart size (24). These changes lead to a further increase in stroke volume or cardiac output through a Starling-type mechanism (5). AoP increased only 7.7 mmHg. It is 9 mmHg (11.7 cmH2O) lower than dynamic change in CAP. The difference is also probably due to the loss of gravitational hydrostatic pressure gradient and height difference between measuring points of CAP and AoP. The measuring point of CAP is higher than HIP, and changes in CAP are +1.8 mmHg from that in 1 G, as discussed above. However, the measuring point of AoP is lower than HIP, and changes in AoP should be –7.2 mmHg from that in 1 G due to a decrease in hydrostatic pressure at the point.
In conclusion, MBF significantly increased, and the vascular resistance is decreased on entry into rG in the anesthetized HUT rats. CBF changed due to the change in the cerebral perfusion pressure, but the vascular resistance remained fairly constant, unlike that in the temporal muscle. These results indicate that vascular control mechanism is different between cerebral cortex and temporal muscle during rG despite the same height. On entry into rG, the increase in CAP is significantly greater than that in AoP, possibly due to the regional change in hydrostatic pressure at each height.
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GRANTS
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This research is supported by a "Ground-based research for space utilization" research grant from Japan Space exploration Agency and Japan Space Forum.
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ACKNOWLEDGMENTS
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The authors thank the pilots and ground support staffs for parabolic flights (Diamond Air Service, Aichi, Japan). The authors also appreciate the technical advice provided by Gotoda (Omega Wave, Tokyo, Japan).
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FOOTNOTES
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Address for reprint requests and other correspondence: K. Tanaka, Dept. of Physiology, Gifu Univ., Graduate School of Medicine, Gifu, 501-1194, Japan (e-mail: kutanaka{at}cc.gifu-u.ac.jp)
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.
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