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Departments of 1 Endocrinology, 2 Anesthesiology, and 3 Vascular and Renal Diseases, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Venous compliance in the legs of aging man has been found to be reduced with decreased blood pooling (capacitance response) in dependent regions, and this might lead to misinterpretations of age-related changes in baroreceptor function during orthostasis. The hemodynamic response to hypovolemic circulatory stress was studied with the aid of lower-body negative pressure (LBNP) of 60 cmH2O in 33 healthy men [18 young (mean age 22 yr) and 15 old (mean age 65 yr)]. Volumetric technique was used in the study of capacitance responses in the calf and arm as well as transcapillary fluid absorption in the arm. LBNP led to smaller increase in heart rate (P < 0.001) and peripheral resistance (P < 0.01) and reduced transcapillary fluid absorption in the arm (P < 0.05) in old subjects. However, blood pooling in the calf was reduced in old subjects (1.66 ± 0.10 vs. 2.17 ± 0.13 ml/100 ml tissue; P < 0.01). Accordingly, during similar blood pooling in the calf (LBNP 80 cmH2O in old subjects), no changes in cardiovascular reflex responses with age were found. The capacitance response in the arm (mobilization of peripheral blood to the central circulation) was still reduced, however (0.67 ± 0.10 vs. 1.37 ± 0.11 ml/100 ml tissue; P < 0.01). Thus the reduced cardiovascular reflex response found in the elderly during orthostatic stress seems to be caused by a reduced capacitance response in the legs with age and a concomitant smaller central hypovolemic stimulus rather than a reduced efficiency of the reflex response. With similar hypovolemic circulatory stress, no changes in cardiovascular reflex responses are seen with age. The capacitance response in the arm (mobilization of peripheral blood toward the central circulation) is reduced, however, by ~50% in the elderly. This might seriously impede the possibility of survival of an acute blood loss.
aging; venous compliance; baroreceptors; lower-body negative pressure
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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SEVERAL GROUPS have found reduced
baroreceptor efficiency with aging, which might reduce the capacity to
preserve homeostasis during hypovolemic circulatory stress induced by
orthostasis or hemorrhage (13, 22). Also, the possibility of
compensating for reduced circulating blood volume by means of
transcapillary fluid absorption from skeletal muscle and skin to the
intravascular space might be reduced, because this is controlled by
sympathetic 
- and 
-receptors in the microcirculation (37, 38).
When experimental approaches such as lower-body negative pressure
(LBNP) and tilting are used, age-related differences in unloading of central baroreceptors might lead to misinterpretations in changes of
baroreceptor function, and techniques that do not unload baroreceptors, such as the cold-pressor test, have shown unchanged sympathetic reflex
responses (8, 15). One confounding factor might be a reduced compliance
of the cardiopulmonary walls, where volume (stretch) receptors are
situated, because an attenuated reduction in left ventricular diastolic
diameter is seen with age during hypovolemic stress caused by LBNP (8).
An alternative explanation might be a decline of the venous capacitance
response in the lower limbs with age, thereby reducing the decrease in
central blood volume during orthostatic stress and thus the
deactivation of baroreceptors. Ebert et al. (14) found a smaller
decrease in thoracic blood volume during similar levels of lower body
suction in old compared with young individuals, suggesting a smaller
shift in thoracic blood volume to the lower extremities. This is in accordance with findings in our laboratory (33, 46) showing a reduction
in venous compliance with a concomitant decrease of the capacitance
response in dependent regions with age. The aim of this study was to
reevaluate the age-related changes during hypovolemic circulatory
stress found in the baroreceptor reflex function in humans, bearing
these confounding factors in mind.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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A total of 33 healthy male volunteers were divided into two separate age groups: 18 young (mean age 22 yr) and 15 old (mean age 65 yr) volunteers. Physical examination showed the absence of varicose veins, hypertension, diabetes, or other serious systemic diseases. All subjects were nonsmokers and were not taking any medication. Each subject gave informed consent to the experiments approved by the Ethics Committee of Lund University, Sweden. The experiments were started 1 h after a regular meal in the morning or at noon and were performed at a room temperature of 22-24°C. The subjects were instructed to abstain from coffee or tea on the day of the investigation. Throughout the experiments, which lasted ~3 h, continuous efforts were made to maintain a relaxed, quiet atmosphere.
Cardiovascular response to hypovolemic circulatory stress. The first part of the study was conducted on 24 of the 33 subjects: 12 young (mean age 22 yr; range 20-25 yr) and 12 old (mean age 65 yr; range 61-70 yr) subjects.
The subjects were placed in a supine position with the legs enclosed in an airtight box up to the level of the iliac crest with a rubber seal fitted hermetically around the waist. The box was connected to a vacuum source, permitting stable negative pressure to be rapidly produced (within 5 s) (LBNP). LBNP is a well-established technique in the study of orthostatic stress, is noninvasive and relatively comfortable to the subjects, and can also be discontinued quickly, promoting safety. The advantage of LBNP compared with passive tilt is that the subject remains at rest in the supine position, which facilitates physiological measurements and minimizes the likelihood of confounding activity in skeletal muscle. Furthermore, the transmural pressure change over the vascular walls is easier to define. LBNP of
40 to 50 mmHg
and passive tilt of 90° cause similar shifts in blood volume,
although the distribution of the pooled blood is probably not the same
because of the differences in transmural pressure gradients (3, 49,
65). The negative pressure in the LBNP chamber was measured
continuously by a manometer (DT-XX disposable transducer, Viggo
Spectramed, Helsingborg, Sweden) and held constant by a rheostat.
After at least 45 min of supine rest LBNP was rapidly instituted within
5 s and maintained for 8 min at 60 or 80 cmH2O. Two experiments were
performed with at least 30 min between each investigation to ensure
that the basal state was restored. To define the hypovolemic stimulus
caused by LBNP, the blood pooling in the legs was measured by means of
strain-gauge plethysmography (64). This method is designed for
measuring volume changes (ml/100 ml) of a limb by measurement of the
circumference. Comparison with air-filled plethysmography showed that
reliable results may be obtained (5). The strain gauge was applied at
the maximal circumference of the calf ~15 cm distal to the knee. Care
was taken to place the midpoint of the calf 5 cm below heart level in
all subjects. To avoid any confounding external pressure, the lowest
part of the calf was at least 2 cm above the floor of the vacuum
chamber. At onset, LBNP evoked an initial rapid increase of calf volume
(capacitance response) followed by a slower but continuous rise caused
by net transcapillary fluid filtration from blood to tissue. At
cessation, there was a rapid decrease of the volume corresponding well
with the increase at onset of LBNP (33, 46). The capacitance response was calculated from the volume increase at the onset of LBNP to the
line defined from the filtration slope between 3 and 8 min, because the
capacitance response is terminated within ~3 min (50).
Transcapillary fluid absorption from the upper arm was measured by
plethysmography. The air plethysmographs were cylindrical, 8 cm long,
and made of 3.5-mm-thick transparent plastic. They had openings of
different sizes to fit the upper arms of the subjects. When the
subjects were in the supine position, the right arm was placed at the
level of the heart. To avoid venous stasis caused by the
plethysmograph, the size of the proximal and distal openings was chosen
to be slightly larger than the circumference of the arm. The air slits
between the openings and the skin of the arm were then sealed with a
soft latex compound (Nordsjö, Malmö, Sweden) that did not
cause any additional pressure or irritation to the skin. The proximal,
middle, and distal circumferences of the enclosed segment were
measured, and the volume was calculated. Changes in tissue volume were
measured with a piston recorder connected to the plethysmograph. LBNP
was applied when upper arm volume was stable. In the analysis of the
tissue volume responses, abrupt changes are considered to reflect
alterations of regional blood volume, whereas gradual volume changes
reflect net transcapillary fluid transfer (see Fig. 2). This
interpretation of tissue volume changes during acute hypovolemic stress
has been validated with the aid of simultaneously measured blood and
tissue volume changes both in animals (1, 42) and in humans (38). Thus
the capacitance response in the upper arm was measured from the rapid
volume change between baseline volume and the line defined from the
transcapillary fluid absorption both at onset and at cessation of LBNP,
and the mean value was taken as the prevailing capacitance response. At the time of the capacitance response at onset of LBNP the paper speed
was also increased to make it possible to calculate the time(s) for
50% of the total capacitance response to be developed (C50). Mean
transcapillary fluid absorption during the LBNP stimulus was calculated
from the volume decrease after cessation of LBNP compared with baseline
volume before LBNP divided by the duration (8 min; see Fig. 2). To
avoid any influence of the hyperemic reaction, present in some of the
recordings immediately after LBNP, and to be sure that the blood volume
had returned to baseline level, the measurement of the change in volume
in relation to baseline was performed 1 min after discontinuation of
LBNP. Two experiments were performed at each LBNP step, and the mean
value was taken as the prevailing capacitance response as well as
transcapillary fluid absorption.
Arterial blood pressure was measured noninvasively in the left upper
arm with a semiautomatic blood pressure device (model HEM-700C, Omron,
Tokyo, Japan). Mean arterial pressure (MAP) was taken as the diastolic
pressure plus one-third of the pulse pressure.
The electrocardiogram signal, the plethysmograph recording, the
pressure in the LBNP chamber, and the calf volume were amplified (PC
polygraph, Synetics Medical, Stockholm, Sweden) and collected with a
modified computer program for medical examination (Gastrosoft polygram,
Synetics Medical) on a personal computer (SPC 386, SPC Trading,
Uppsala, Sweden).
In separate experiments on the subjects, blood flow was measured on the
right forearm by standard venous occlusion (50 mmHg) mercury-in-silicone elastomer (Silastic) strain-gauge plethysmography (Hokanson EC-4 D.E, Hokanson). The forearm was placed ~5 cm above the
level of the right atrium, and the strain gauge was placed 5 cm distal
to the elbow. Occlusion of hand blood flow was accomplished by a wrist
cuff inflated to 100 mmHg above systolic arterial pressure 1 min before
measurements (32). A computerized R wave-trigged system was used for
measurement of forearm blood flow using the first three to six heart
beats after institution of occlusion plethysmography (7). The blood
flow was measured six times at baseline and twice at 30 s and 1, 3, 6, and 8 min after institution of LBNP and 1, 2, and 4 min after LBNP was
discontinued. Peripheral resistance was calculated as MAP divided by
blood flow. Data are given with reference to soft tissue weight
excluding bone. Bone is taken as 10% in the upper arm and calf (29)
and 13% in the forearm (9).
In other experiments on 6 of the young and 10 of the old subjects, a
polyethylene catheter was inserted into an antecubital vein for blood
sampling to measure plasma norepinephrine, which has been shown to be a
good marker for the general sympathetic activation (16). LBNP at 60 and
80 cmH2O was applied as described above. Blood samples (3 ml) were taken from the vein before and at the
end of each LBNP level. The blood samples were collected in prechilled
tubes containing 5.7 mg of EGTA and 3.6 mg of reduced glutathione and
kept on ice until centrifuged at 4°C within 30 min. The plasma was
stored at 80°C. Venous plasma (VP) norepinephrine was
analyzed with HPLC (18). The duration of the LBNP stimulus was 4 min
because, during this period, the increase in venous norepinephrine is
almost completely developed (17).
Venous compliance in the calf. The second part of the study was performed on 11 of 33 subjects [6 young (median age 22 yr, range 20-24 yr) and 5 old (median age 64 yr, range 60-66 yr) subjects], in whom venous compliance was studied in the right calf. With the subjects placed in a supine position, the skin and muscle fascia of the posterolateral muscle tissue compartment at the level of maximal circumference of the lower leg, ~15 cm distal to the knee, was anesthetized by 1-2 ml of lignocaine (10 mg/ml; Astra, Södertälje, Sweden). A needle surrounded by a polyethylene catheter with an outer diameter of 1.7 mm was inserted perpendicular to the skin into the lateral gastrocnemius muscle (Venflon, Viggo Spectramed). The needle was withdrawn, and a 0.7-mm (ID) Teflon catheter with four side holes (Myopress, Athos Medical, Hörby, Sweden) was inserted via the Venflon catheter, after which the Venflon was withdrawn. The pressure catheter was fixed with adhesive tape to the skin and connected to a pressure transducer (DT-XX disposable transducer, Viggo Spectramed), which was placed at the height that corresponded to the midpoint of the studied tissue segment of the calf ~5 cm below heart level. A three-way stopcock close to the pressure transducer was used to connect the pressure catheter to a pump (Perfuser Secura FT, B. Braun, Kronberg, Germany) delivering saline at 0.5 ml/h during the experiment to preserve catheter patency. In each subject, tests on the dynamic function of the pressure-recording system were performed at the beginning of the experiment by applying external compression to the tissue and asking the subject to perform active muscle contractions. These procedures normally resulted in rapid changes in the recorded pressure. When occasionally such tests produced unusually slow and small pressure deflections, or if there was retrograde filling of blood into the catheter, this was taken as a sign of inadequate catheter patency. In these cases, the catheter was removed and a new one was inserted at an adjacent site. The test with active muscle contractions was also performed at intervals between the experiments, and in a few cases there were signs of deterioration in catheter patency. Data from such recordings were omitted from the results presented.
After the catheter was inserted at a 4-cm depth, the legs were enclosed in the LBNP chamber as described in Cardiovascular response to hypovolemic circulatory stress. Applied negative external pressure has been shown to be transmitted into the tissue, causing an increase in transmural vascular pressure with only transient effects on intravascular pressure (2, 36). Because compliance of the arterial bed is only ~3% of that of the venous bed, almost exclusively venous blood is pooled in the lower part of the body, with the degree of pooling proportional to the negative pressure. The subsequent volume increase was calculated by means of strain-gauge plethysmography with the strain gauge placed around the maximal calf circumference ~15 cm below the knee and adjacent to the insertion of the pressure catheter. The subject was lying supine in the box with the left foot resting on a wooden plate to counter the suction force created by the negative box pressure. The right foot had no contact with the plate, to avoid muscle tension in the calf because this may affect muscle pressure and induce mechanical compression of the vascular tree (51, 54). Care was taken to place the midpoint of the right calf 5 cm below heart level in all subjects. To avoid any confounding external pressure the lowest part of the calf was at least 2 cm above the floor of the vacuum chamber. Between each period of reduced external pressure, tissue pressure and calf volume were allowed to return to control levels. Repetitive analyses gave no indication that pressure transmission deteriorated with time or that control pressure increased with time because of possible edema formation. Tissue pressure was not affected by the discrete saline infusion, because no pressure changes were seen during arrested infusion. The applied transmural vascular pressure gradient was calculated from the measured tissue pressure change during LBNP, with the prevailing control level as baseline. The basic data from these experiments have already been reported (46), and this part of the study only addressed the possibility of mobilizing capacitance blood from skeletal muscle and skin to the central circulation during a standardized reduction of venous transmural pressure. Thus, initially, LBNP of 42 mmHg (increase in venous transmural pressure) was applied for 4 min to allow complete filling of the capacitance vessels (50). The applied external negative pressure was then reduced in a standardized linear fashion (0.35 mmHg/s) from 42 to 0 mmHg (120 s), during which the changes in tissue pressure and calf volume, i.e., capacitance response, were continuously collected. Because the veins account for 97% of the vascular compliance, this is denoted venous compliance (Cv, ml · 100 ml
1 · mmHg1)
Cv was then calculated
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(1) |
V denotes a change in calf volume (ml/100 ml) and P denotes a
change in muscle pressure (mmHg). The calculations were performed for
every 5-cmH2O (3.7 mmHg) decrease
of tissue pressure and were related to the induced level of transmural
pressure. At least two experiments were performed in all individuals,
and the mean values were calculated.
Statistical evaluation. Values are expressed as means ± SE. Area under the curve for the changes in heart rate, blood pressure, forearm blood flow, and peripheral resistance was calculated. The significance of difference between the two groups was tested by unpaired Student's t-test. To study Cv in the calf, a nonlinear mixed model was used that included Cv as a dependent variable and transmural pressure change as a covariate variable. The two groups of subjects (young and old) were included as fixed parameters, and the individual subjects as random-effect parameters. P < 0.05 was considered statistically significant.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Table 1 shows resting hemodynamic values in
young and old subjects. It is seen that the old subjects had higher
diastolic pressure and MAP (P < 0.001). Also, VP norepineprine was higher in the old than in the young
subjects (1.9 ± 0.2 vs. 1.1 ± 0.1 pmol/l;
P < 0.05).
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Both the young and old subjects showed good homogeneity of responses to hypovolemic circulatory stress and tolerated LBNP of 60 cmH2O (LBNPortho) well with no symptoms. One of the young men developed a more pronounced fall in systolic blood pressure and decrease in heart rate (vagal reaction) on one occasion. The results from this experiment are excluded.
Figure 1 shows the cardiovascular responses
in young and old subjects during the hypovolemic stress caused by 8-min
LBNPortho. This shows a
progressive increase in heart rate and decrease in pulse pressure. The
forearm blood flow decreased because of an increase in peripheral
resistance. The increase in heart rate was lower
(P < 0.001) and the decrease in
systolic blood pressure was less prominent
(P < 0.05) in old compared with
young subjects. Furthermore, the increase in peripheral vascular
resistance was lower in old subjects
(P < 0.01), with a less-pronounced
reduction in forearm blood flow (P < 0.01).
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Figure 2,
left, shows a representative original
recording in a 20-year-old subject, illustrating the changes of tissue
volume in the upper arm caused by
LBNPortho. There is an initial
rapid decline of tissue volume, followed by a much slower but
continuous decrease throughout the 8-min period of LBNP. At cessation
of LBNP, tissue volume rapidly increased again and tended to stabilize for a few minutes on a new level lower than that before LBNP. Later,
there was a slow and gradual increase toward the initial control level.
Previous analyses (see MATERIALS AND
METHODS) showed that this train of events reflects
1) an initial mobilization of
regional blood toward the central circulation at onset of LBNP (capacitance response), followed by
2) a net transcapillary fluid absorption of fluid from the extra- to the intravascular space, and
3) on cessation of LBNP, by a rapid
regain of regional blood content back to control level. The subsequent
slow increase of tissue volume represents a transcapillary filtration
of fluid that gradually restores the fluid volume prevailing in the
tissue before LBNP. The capacitance response was 1.40 ml/100 ml, and the transcapillary fluid absorption was 0.097 ml · 100 ml1 · min1.
Figure 2, right, shows a
representative recording in a 61-year-old subject during 8-min
LBNPortho. The capacitance
response was reduced by 50% to 0.61 ml/100 ml and the transcapillary
fluid absorption by 30% to 0.062 ml · 100 ml1 · min1
compared with the young subject.
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Figure 3A
shows that the capacitance response, i.e., the blood mobilization from
the upper arm to the central circulation, during
LBNPortho was decreased in old
compared with young subjects (0.64 ± 0.07 vs. 1.37 ± 0.11 ml/100 ml; P < 0.001). Also,
transcapillary fluid absorption (Fig.
3B) was lower in old compared with
young subjects (0.068 ± 0.007 vs. 0.091 ± 0.008 ml · 100 ml1 · min1;
P < 0.05).
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During LBNPortho, VP norepinephrine increased significantly (95 ± 28% in young and 61 ± 7% in old subjects; P < 0.001). The difference in increase between young and old was not significant (NS).
The blood pooling in the calf during LBNPortho was significantly lower in old compared with young subjects (1.66 ± 0.10 vs. 2.17 ± 0.13 ml/100 ml; P < 0.01). To accomplish similar hypovolemic circulatory stress (blood pooling in the lower part of the body), the LBNP stimulus was increased in a separate study to 80 cmH2O in old subjects (LBNPhypo). Of the 12 old individuals investigated with LBNPortho, 10 agreed to be included in the LBNPhypo study. One of these developed a more pronounced fall in systolic blood pressure and decrease in heart rate (vagal reaction) 1 min after onset of LBNP and was excluded. Thus data from nine old subjects were included when the hemodynamic circulatory responses to LBNPhypo were calculated. The hemodynamic responses to LBNPortho in the three individuals who did not participate in the LBNPhypo study did not differ compared with the study group. Blood pooling in the calf during LBNPhypo was found to be similar (2.23 ± 0.24 vs. 2.17 ± 0.13 ml/100 ml in old and young subjects; NS).
Figure 4 shows the hemodynamic responses to
LBNPhypo in the two
groups. There were no significant differences in the changes of heart
rate or blood pressure between the young and old subjects. There was a
slightly lower heart rate increase in the old subjects (P = 0.06). Furthermore, the
increase in peripheral resistance was similar, with a concomitant equal
reduction in forearm blood flow.
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Figure 5A
shows that the capacitance response, i.e., the blood mobilization from
the upper arm to the central circulation, during
LBNPhypo was still
significantly decreased by ~50% in the old subjects (0.67 ± 0.10 vs. 1.37 ± 0.11 ml/100 ml in old and young subjects;
P < 0.001). Figure
5B shows that the transcapillary fluid
absorption during LBNPhypo was
similar (0.091 ± 0.008 vs. 0.090 ± 0.009 ml · 100 ml1 · min1
in young and old subjects; P = NS). No
difference in venous norepinephrine increase (%) during
LBNPhypo was seen (95 ± 28 and
87 ± 15% in young and old subjects, respectively;
P = NS).
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Figure 6 shows the venous compliance in the
calf in young and old subjects. Only the decrease in transmural
pressure from 18 mmHg downward is shown. This reveals that the
compliance increased significantly both in young
(P < 0.0001) and old
(P < 0.005) subjects during a
decrease in transmural pressure gradient. In the young subjects the
increase in compliance, especially at low transmural pressures, was
nonlinear and much more apparent than in the old subjects
(P < 0.0001). For comparison,
earlier published values on Cv
calculated at higher transmural pressure gradients (interval 18-51
mmHg) in young and old subjects are also depicted in Fig. 6. This shows
a reduced Cv in the old subjects;
however, this was not pressure dependent (46).
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The time for 50% of the capacitance response in the upper arm to be developed (C50), i.e., the mobilization of the regional blood content from the upper arm to the central circulation, was calculated during LBNPhypo (similar hypovolemic circulatory stress in young and old subjects). This showed that C50 was significantly longer in the old than in the young subjects (16.4 ± 1.1 vs. 9.4 ± 0.9 s, respectively; P < 0.001).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Venous compliance Cv in the legs has been found to be reduced with age in humans, with a concomitant reduction in capacitance response (33, 46). This affects the blood pooling in dependent regions and might be a confounding factor in the study of cardiovascular responses during hypovolemic circulatory stress with experimental approaches such as LBNP and tilting, leading to misinterpretations in the changes of baroreceptor responses with age. The aim of this study was to reevaluate the changes found in baroreceptor function with age with confounding factors borne in mind. A reduced compensatory baroreceptor reflex response was found with age during a LBNP-induced orthostatic stimulus (LBNPortho, 60 cmH2O in young and old subjects), with smaller increases in heart rate and peripheral resistance as well as reduced transcapillary fluid absorption from skeletal muscle and skin to blood. This was found to be caused by reduced blood pooling (capacitance response) in the legs in response to LBNP with a concomitant smaller central hypovolemic stimulus in the old subjects rather than reduced efficiency of the reflex response. With similar blood pooling in the lower part of the body [LBNP 60 cmH2O vs. 80 cmH2O (LBNPhypo) in young and old subjects], and thus presumably similar central hypovolemic circulatory stress, no differences in the compensatory baroreceptor reflex responses with age were found. Our study implies that the reduced efficiency in the baroreceptor reflex axis found in earlier studies (22, 13) is well compensated with age. However, the capacitance response in skeletal muscle and skin not exposed to an increased hydrostatic pressure load, i.e., the first line of defense during hypovolemic circulatory stress (leading to mobilization of peripheral blood toward the central circulation, increasing the effective circulating blood volume), was reduced in the old subjects (Fig. 5). This might seriously impede the possibility of survival of an acute blood loss.
LBNP was used in this study to pool blood in the capacitance vessels in
the lower part of the body to create central hypovolemia to explore
baroreceptor function changes in aging. During
LBNPortho in young and old healthy
subjects we found a reduced increase in heart rate with age, which
earlier was related at least partly to an attenuation of responses to
-adrenergic agonists (Fig. 1; Refs. 13, 22, 56, 60, 63), although
limitations in the withdrawal of parasympathetic tone affecting the
initial phase of cardioacceleration may also play a role (59, 63).
Reduced -receptor-mediated responsiveness with attenuated
vasoconstriction was found with increasing age in humans in both in
vivo and in vitro studies (31, 44, 57). This may be the reason for the
elevated muscle sympathetic nerve activity (MSNA) found in older
humans, being compensatory sympathetic adjustments that offset
declining effector responses (12, 15, 43, 57). Furthermore, the active
transmitter reuptake mechanism seems to be attenuated, and these
mechanisms are likely to explain the elevated resting plasma
norepinephrine level found in the old subjects (Table 1; Ref. 20). MSNA
responses to intravenous administration of vasodilatory drugs are not
impaired, and baroreflex control of MSNA during orthostatic stress
seems rather to be augmented with advancing age in healthy humans (12).
Despite these facts, we found an attenuated forearm vasoconstrictor
response to sympathetic stimulation induced by
LBNPortho in the old subjects
(Fig. 1). This could have been caused by a smaller release from
sympathetic nerve endings and consequent lower synaptic concentration
of norepinephrine. This seems to be refuted, however, by the increase
in norepinephrine concentration during orthostatic stress that was
similar in the two groups and by the fact that norepinephrine clearance
decreases with age (19, 20).
There was a compensatory increase in circulating effective blood volume
in response to the hypovolemic circulatory stress caused by
LBNPortho, accomplished both by
mobilization of blood from capacitance vessels and by net
transcapillary fluid absorption from skeletal muscle and skin not
exposed to hydrostatic pressure load (Fig. 2; Ref. 38). The
transcapillary fluid absorption is caused by deactivation of central
baroreceptors with a concomitant sympathetic stimulation. This
establishes a reflex decline in capillary pressure caused by - and
-adrenergic adjustment of the precapillary-to-postcapillary
resistance ratio, initiating a transcapillary driving force (37, 41).
Both capacitance response and fluid absorption were significantly
reduced in the old subjects with a defective compensatory increase in
effective circulating blood volume in response to the hypovolemic
situation (Fig. 3). The reduced fluid flux could have been caused by
decreased responses to adrenergic - and -receptor agonists (31,
44, 57, 60). Another possibility that would affect the fluid absorption is a reduction of capillary fluid permeability and area in skeletal muscle and skin available for fluid exchange with age. This
possibility, however, seems incompatible with earlier studies that
showed no such changes in capillary fluid permeability characteristics
(25, 33).
Thus, in older humans, there seems to be a generalized reduction in baroreceptor reflexes in response to orthostasis (Figs. 1 and 3; Refs. 8, 14, 22, 61). These findings could result in more pronounced blood pressure alterations, and postural hypotension has been reported to be common in the elderly. Most studies on the capacity of the cardiovascular system to adapt to orthostatic stress in old age, however, have included more or less disabled persons or patients with physical inactivity, bed rest, obesity, or cardiovascular disease, which can independently influence autonomic circulatory control during orthostasis (24, 39, 40, 55). In contrast, Mader (40) reported that postural hypotension is a relatively uncommon finding in healthy elderly persons and that its prevalence is significantly related to risk factors. In fact, our data show a less-pronounced blood pressure fall during orthostatic stress in the old subjects despite a smaller increase in peripheral vascular resistance or reflex tachycardia (Fig. 1) and confirm earlier studies on healthy old subjects (12, 58). The lack of decline in arterial systolic and pulse pressures in the old subjects during orthostasis suggests that the central baroreceptors may not have been unloaded to the same extent as that observed in the young subjects. Thus the absence of a significant increase in peripheral vascular resistance and heart rate should not necessarily be interpreted as evidence for impaired arterial baroreflex control with aging (Fig. 1). An alternative explanation for the maintained regulation of arterial pressure despite an attenuated peripheral vasoconstriction in the old could be a smaller challenge to arterial blood pressure maintenance caused by decreased venous capacitance response with age in the lower limbs. This would reduce the decrease in central blood volume and, thus, the deactivation of baroreceptors. A smaller decrease in thoracic blood volume as well as in cardiac output was found during orthostatic stress in old compared with young subjects, suggesting a smaller shift in central blood volume to the lower extremities (14, 21). This is in accordance with the data presented here as well as earlier findings in our laboratory (33) showing a reduced capacitance response of the lower limbs with age. Frey and Hoffler (23) did not find such a reduction, however, but the age range in their study was lower, making the putative differences more difficult to detect. The causative factor for the reduction in capacitance response seems to be a reduced venous compliance in the lower limbs that decreases ~45% between 20 and 60 yr of age in healthy subjects (46). A possible explanation for the changes in vein compliance with a concomitant decrease in capacitance function might be the increase in collagen-to-elastin ratio as well as wall thickening found in veins with age (4).
To reveal the true physiological changes with age resulting from the chain of baroreceptor deactivation-sympathetic discharge-effector response, it is of fundamental importance to equalize the hypovolemic stimulus between young and old subjects. This was accomplished in separate experiments by using LBNP at 80 cmH2O (LBNPhypo) instead of 60 cmH2O in the old subjects, which led to similar blood pooling in the lower part of the body and, thus, presumably similar central hypovolemic circulatory stress in the two groups (see RESULTS).
The reflex cardiovascular response in the old subjects now reveals systolic blood pressure fall and reduction in pulse pressure similar to that in the young subjects (Fig. 4), suggesting that the baroreceptors may have been unloaded to the same extent in young as in old subjects. The resulting increases in peripheral vascular resistance and heart rate as well as the transcapillary fluid absorption from skeletal muscle and skin to blood were similar in the two groups (Figs. 4 and 5). These results are consistent with the study of Cléroux et al. (8) that showed unchanged sympathetic reflex responses to cold-pressor test with age, and they might be interpreted as evidence for a sustained arterial baroreflex control during aging (Fig. 4).
Although the baroreflex control seems to be sustained in elderly subjects, it is of interest to note the association between substantial hypotension and gastrointestinal vasodilatation during digestion as well as fluid loss or sodium depletion that has been found in elderly subjects (35). Blood volume is lower in older than in young humans, which might be related to total cell mass as well as to the level of physical activity in the elderly (11). Furthermore, fluid intake was reported to be decreased and fluid excretion by the kidneys increased in older subjects (52). Thus dehydration from whatever cause was shown to have more profound effects in the elderly, and a limitation in blood pressure homeostasis may be unmasked after a modest physiological stress such as diuretic-induced loss of sodium and reduction of extracellular volume (53).
A possible explanation for the increased cardiovascular susceptibility to hypovolemic challenge might be the fact that the capacitance response to hypovolemic circulatory stress, i.e., the mobilization of venous blood to the effective circulating blood volume, was reduced by 50% in old subjects (Figs. 3A and 5A). The veins can be looked upon as a voluminous reservoir containing 85% of the total blood volume that is designed to preserve a proper inflow of blood into the heart (49). The pronounced capacity and low resistance of this vascular section imply that even small pressure reductions in the central veins are followed by substantial mobilization of blood from peripheral vascular beds toward the heart. Although in vivo experiments on subcutaneous veins provided evidence for sympathetic constrictor responses (34), no evidence exists that active venoconstriction of capacitance vessels in skeletal muscle (40-45% of body wt) provides an important mechanism translocating blood into the central circulation (28). Thus the main part of the venous reservoir is adjusted simply by means of passive changes. The reduced capacitance response in the old subjects could be a result of several factors. The differences in body weight between the groups, with a larger weight in the old subjects, might introduce an error in the estimation of the soft tissue-to-bone ratio (Table 1). An increased amount of soft tissue in the arm would indicate an overestimation of the capacitance response and an underestimation of the differences between the groups. Furthermore, muscle atrophy that may occur with aging seems to increase Cv, at least in the calf, and would thus also lead to an underestimation of the differences in capacitance response between young and old subjects (6). Another confounding factor might be differences in venous filling before LBNP. The capacitance of an anatomic area relates the total volume contained within the vasculature to the prevailing transmural pressure. In our experiments, no measurements were made of the amount of blood held in the upper arm before the application of suction (V0), and there is no reason to believe that this volume is constant. To avoid inappropriate differences in V0 between individuals, care was taken to place the arms at the same level. Furthermore, the subjects rested at least 45 min before institution of LBNP, during which time arm volume and blood flow became stabilized (see MATERIALS AND METHODS). Our experiments were then concerned with the quantity of blood that was mobilized from the upper arm in response to the hypovolemic circulatory stress caused by LBNP. Because of the high Cv, small changes in intravenous pressure, owing to changes in blood flow, will have marked effects on venous volume. During LBNP arteriolar resistance increases by sympathetic stimulation of the arterial smooth muscle, and the flow tends to decrease (Figs. 1 and 4). This in turn decreases the pressure gradient from capillaries to large veins and the average small vein pressure decreases (48). Because the decrease in blood flow was attenuated during LBNPortho in the old subjects (Fig. 1), this might have led to differences between the groups, with a relatively larger venous volume in the older group which would result in an overestimation of the differences in capacitance response (48). During LBNPhypo, however, with a similar reduction in blood flow between the groups, the capacitance response was still 50% lower in the old subjects (Fig. 5). Thus the conclusion is reached that the hypothesis of venous capacitance decline with age is valid.
The decline in capacitance might be caused by the increase in collagen-to-elastin ratio as well as wall thickening found in the veins with age (4), with stiffening as a consequence. An increased venous stiffness was shown earlier in both arms and legs in humans, analogous to the known increase in arterial wall stiffness with age (26, 30, 46). The stiffness of a vein can be ascribed quantitatively in terms of a relationship between its volume and distending (transmural) pressure. This is nonlinear, and at low pressures a small change in pressure leads to a large change in volume, so that compliance is high. The early expansion phase of the veins involves no actual stretch of the elastic material in its wall, and a small change in distending pressure merely changes the geometry of the veins (45, 47). Once the veins have assumed a circular cross section, subsequent increases in their transmural pressure are opposed by the development of increased tension in the walls, and at higher pressure compliance is lower (62). In the experiments on Cv in the calf no data on baseline venous pressure were collected, which might be a confounding factor in the study of Cv. The precautions adopted in our protocol, however, make this unlikely (see MATERIALS AND METHODS). Another factor of concern might be differences in transmission of the applied external negative pressure around the calf in young and old subjects, with a concomitant difference in applied transmural pressure gradient. This seems refuted, however, by the fact that 80% of the pressure is found to be transmitted in both young and old subjects (46). Our recent study (46) showed reduced Cv in old subjects and was focused on the part of the volume-pressure curve that had assumed linearity (transmural pressure increase 18-51 mmHg), indicating that the venous section containing the majority of the blood volume, i.e., the venules, had assumed a circular cross-sectional area. In the present investigation, however, the attention was focused on the lower, more compliant level of the volume-pressure curve, i.e., where even small transmural pressure changes in the peripheral veins are followed by substantial differences in central blood volume. This part of the curve is the principal culprit for mobilization of venous blood to the effective circulating blood volume during hypovolemic circulatory stress. It is of interest to note that the venous compliance showed a much more rapid increase, especially in the lowest part of the curve, in the young rather than in the old subjects (Fig. 6).
The rate of the capacitance response (mobilization of blood from skeletal muscle and skin) in the arm during hypovolemic circulatory stress was also found to be slower in the old subjects. Thus it seems that not only the amount of blood that may be mobilized but also the rate of mobilization is reduced in the old. The volume-pressure curve of a limb at rest represents the distributed properties of all veins (microvessels to large veins). Factors other than venous properties may affect this curve, such as rigid fascia that restricts expansion, especially in the upper part of the curve. In the lower part of the volume-pressure curve, extensive tethering of veins may limit their emptying and changes in the tethering might perhaps be an explanation for the demonstrated differences with age; however, data are lacking in this context. The volume-pressure relationship will also be affected by the vascular anatomy, which determines how large a fraction of the total volume is distributed within the smallest veins as opposed to the largest ones. This means that total Cv of the limbs depends on the size, relative number, and wall structure of each venous segment. Another factor of importance is the resting state of the muscles, because muscle contraction increases muscle pressure and affects Cv (10, 51).
The pathophysiological significance of the changes in the venous system with age has clinical implications. In fact, this crucial first line of defense comes into play within seconds during an acute hypovolemic circulatory stress, where both the compensatory increase in effective circulating blood volume and the rate of compensation are important factors to preserve homeostasis (Fig. 2). Thus this might seriously impede the possibility of survival of acute blood loss in the aging.
In conclusion, a reduced compensatory baroreceptor reflex response was found with increasing age during a LBNP-induced orthostatic stimulus, with a smaller increase in heart rate and peripheral resistance as well as reduced transcapillary fluid absorption from skeletal muscle and skin into blood. This seems to be caused by reduced blood pooling (capacitance response) in the legs in response to LBNP with a concomitant, smaller central hypovolemic stimulus in the elderly rather than a reduced efficiency of the reflex response. With similar blood pooling in the lower part of the body as in the young, and thus presumably similar central hypovolemic circulatory stress, no differences in the compensatory baroreceptor reflex responses with age were found. This implies that the reduced efficiency in the baroreceptor deactivation-sympathetic discharge-effector response that was reported previously, is well compensated with age. However, the capacitance response in skeletal muscle and skin not exposed to an increased hydrostatic pressure load, i.e., the first line of defense during hypovolemic circulatory stress (leading to mobilization of peripheral blood toward the central circulation increasing the effective circulating blood volume), showed a 50% reduction in the old subjects. This might seriously impede the possibility of survival of an acute blood loss.
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ACKNOWLEDGEMENTS |
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The authors thank Dr. Britt-Marie Jacobson, Bioanalytical Chemistry, Astra Hässle AB, Mölndal, Sweden, for the analyses of norepinephrine.
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FOOTNOTES |
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This study was supported by grants from the Medical Faculty, Lund University, Medical Research Council Grant 12661, and the Funds of Malmö University Hospital.
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. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: T. Länne, Dept. of Vascular and Renal Diseases, Malmö Univ. Hospital, S-205 02 Malmö, Sweden (E-mail: toste.lanne{at}kir.mas.lu.se).
Received 5 April 1999; accepted in final form 11 August 1999.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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|---|
1.
Åblad, B.,
and
S. Mellander.
Comparative effects of hydralazine, sodium nitrite and acetylcholine on resistance and capacitance blood vessels and capillary filtration in skeletal muscle in the cat.
Acta Physiol. Scand.
58:
319-329,
1963.
2.
Aratov, M.,
S. Fortney,
D. Watenpaugh,
A. Crenshaw,
and
A. Hargens.
Transcapillary fluid responses to lower body negative pressure.
J. Appl. Physiol.
74:
2763-2770,
1993
3.
Blomqvist, C. G.,
and
H. L. Stone.
Cardiovascular adjustments to gravitational stress.
In: Handbook of Physiology. The Cardiovascular System. Peripheral Circulation and Organ Blood Flow. Bethesda, MD: Am. Physiol. Soc, 1983, sect. 2, vol. III, pt. 2, chapt. 28, p. 1025-1063.
4.
Bouissou, H.,
M.-T. Julian,
E. Pieraggi,
J.-C. Maurel Thiers,
and
L. Lounge.
Structure of healthy and varicose veins.
In: Return Circulation and Norepinephrine: An Update, edited by P. M. Vanhoutte. Paris: John Libbey Eurotext, 1991, p. 139-150.
5.
Brakkee, A. J. M.,
and
A. J. H. Vendrik.
Strain-gauge plethysmography: theoretical and practical notes on a new design.
J. Appl. Physiol.
21:
701-704,
1966
6.
Buckey, J. C.,
L. D. Lane,
G. Plath,
F. A. Gaffney,
F. Baisch,
and
C. G. Blomqvist.
Effect of head-down tilt for 10 days on the compliance of the leg.
Acta Physiol. Scand.
144:
53-59,
1992.
7.
Chang, P. C.,
R. Verlinde,
T. Bruning,
and
P. Van Brummel.
A microcomputer-based, R-wave trigged system for hemodynamic measurements in the forearm.
Comput. Biol. Med.
18:
157-163,
1988[ISI][Medline].
8.
Cléroux, J.,
C. Giannattasio,
G. Bolla,
C. Cuspidi,
G. Grassi,
C. Mazzola,
L. Sampiere,
G. Seravalle,
M. Valsecchi,
and
G. Mancia.
Decreased cardiopulmonary reflexes with aging in normotensive humans.
Am. J. Physiol. Heart Circ. Physiol.
257:
H961-H968,
1989
9.
Cooper, K. E.,
O. G. Edholm,
and
R. F. Mottram.
The blood flow in skin and muscle of the human forearm.
J. Physiol.
128:
258-267,
1955.
10.
Crenshaw, A. G.,
S. Karlsson,
B. Gerdle,
and
J. Fridén.
Differential responses in intramuscular pressure and EMG fatigue indicators during low- vs. high-level isometric contractions to fatigue.
Acta Physiol. Scand.
160:
353-361,
1997[ISI][Medline].
11.
Davy, P. K.,
and
D. R. Seals.
Total blood volume in healthy young and older men.
J. Appl. Physiol.
76:
2059-2062,
1994
12.
Davy, P. K.,
D. R. Seals,
and
H. Tanaka.
Augmented cardiopulmonary and integrative sympathetic baroreflexes but attenuated peripheral vasoconstriction with age.
Hypertension
32:
298-304,
1998
13.
Docherty, J. R.
Cardiovascular responses in aging.
Pharmacol. Rev.
42:
103-106,
1990[ISI][Medline].
14.
Ebert, T. J,
C. V. Hughes,
F. E. Tristani,
J. A. Barney,
and
J. J. Smith.
Effect of age and coronary heart disease on the circulatory responses to graded lower body negative pressure.
Cardiovasc. Res.
16:
663-669,
1982[ISI][Medline].
15.
Ebert, T. J.,
B. J. Morgan,
J. A. Barney,
T. Denahan,
and
J. J. Smith.
Effects of aging on baroreflex regulation of sympathetic activity in humans.
Am. J. Physiol. Heart Circ. Physiol.
263:
H798-H803,
1992
16.
Eckberg, D. L,
R. F. Rea,
O. K. Andersson,
T. Hedner,
F. Pernow,
M. Lundberg,
and
B. G. Wallin.
Baroreflex modulation of sympathetic neurotransmitters in humans.
Acta Physiol. Scand.
133:
221-231,
1988[ISI][Medline].
17.
Edfeldt, H.
Sympathetic Baroreflex Control of Vascular Resistance in Skeletal Muscle and Skin of Man (PhD thesis). Växjö, Sweden: Lund University, 1993.
18.
Eriksson, B.-M.,
and
B.-A. Persson.
Determination of catecholamines in rat heart tissue and plasma samples by liquid chromatography with electrochemical detection.
J. Chromatogr.
228:
143-154,
1982[ISI][Medline].
19.
Esler, M. D.,
J. M. Thomson,
D. M. Kaye,
A. G. Turner,
G. L. Jennings,
H. S. Cox,
G. W. Lambert,
and
D. R. Seals.
Effects of aging on the responsiveness of the human cardiac sympathetic nerves to stressors.
Circulation
91:
351-358,
1995
20.
Esler, M. D.,
A. G. Turner,
D. M. Kaye,
J. M. Thomson,
B. A. Kingwell,
M. Morris,
G. W. Lambert,
G. L. Jennings,
H. S. Cox,
and
D. R. Seals.
Aging effects on human sympathetic neuronal function.
Am. J. Physiol. Regulatory Integrative Comp. Physiol.
268:
R278-R285,
1995
21.
Fagard, R.,
P. Lijnen,
J. Staessen,
L. Thijs,
and
A. Amery.
Effect of age on the hemodynamic response to posture in nonelderly hypertensive patients.
Am. J. Hypertens.
7:
30-35,
1994[ISI][Medline].
22.
Folkow, B.,
and
A. Svanborg.
Physiology of cardiovascular aging.
Physiol. Rev.
73:
725-764,
1993
23.
Frey, M. A. B.,
and
W. Hoffler.
Association of sex and age with responses to lower-body negative pressure.
J. Appl. Physiol.
65:
1752-1756,
1988
24.
Frolich, E.,
R. Tarazi,
M. Ulrych,
H. Dustan,
and
I. Page.
Tilt test for investigating a neural component in hypertension.
Circulation
36:
387-393,
1967
25.
Gamble, J.,
D. Bethell,
N. Day,
P. P. Loc,
I. B. Gartside,
and
N. J. White.
The relationship between age and microvascular filtration capacity in man (Abstract).
J. Vasc. Res.
35, Suppl. 2:
31,
1998.
26.
Gascho, J. A.,
C. Fanelli,
and
R. Zelis.
Aging reduces venous distensibility and the venodilatory response to nitroglycerin in normal subjects.
Am. J. Cardiol.
63:
1267-1270,
1989[ISI][Medline].
28.
Gow, B.
Circulatory correlates: vascular impedance, resistance, and capacity.
In: Handbook of Physiology. The Cardiovascular System. Vascular Smooth Muscle. Bethesda, MD: Am. Physiol. Soc, 1980, sect. 2, vol. II, chapt. 14, p. 353-408.
29.
Hafferl, A.
Lehrbuch der topographischen Anatomie. Berlin: Springer, 1957.
30.
Hansen, F.,
P. Mangell,
B. Sonesson,
and
T. Länne.
Diameter and compliance in the human common carotid artery
variations with age and sex.
Ultrasound Med. Biol.
21:
1-9,
1995[ISI][Medline].
31.
Hogikyan, R. V.,
and
M. A. Supiano.
Arterial -adrenergic responsiveness is decreased and SNS activity is increased in older humans.
Am. J. Physiol. Endocrinol. Metab.
266:
E717-E724,
1994
32.
Kerslake, D. M.
The effect of the application of an arterial occlusion cuff to the wrist on the blood flow in the human forearm.
J. Physiol.
108:
451-457,
1949.
33.
Länne, T.,
and
H. Olsen.
Decreased capacitance response with age in lower limbs of humansa potential error in the study of cardiovascular reflexes in aging.
Acta Physiol. Scand.
161:
503-507,
1997[ISI][Medline].
34.
Linder, L.,
B. Lautenschlager,
and
W. Haefeli.
Subconstrictor doses of neuropeptide Y potentiate -1-adrenergic venoconstriction in vivo.
Hypertension
28:
483-487,
1996
35.
Lipsitz, L. A.,
R. P. Nyquist,
J. Y. Wei,
and
J. W. Rowe.
Postprandial reduction in blood pressure in the elderly.
N. Engl. J. Med.
309:
81-83,
1983[Abstract].
36.
Lundvall, J.
Myogenic mechanisms in the control of systemic resistance and transcapillary fluid exchange in man.
J. Hypertens. Suppl.
7:
S85-S91,
1989[Medline].
37.
Lundvall, J.,
and
J. Hillman.
Fluid transfer from skeletal muscle to blood during hemorrhage. Importance of beta-adrenergic vascular mechanisms.
Acta Physiol. Scand.
102:
450-458,
1978[ISI][Medline].
38.
Lundvall, J.,
and
T. Länne.
Large capacity in man for effective plasma volume control in hypovolemia via fluid transfer from tissue to blood.
Acta Physiol. Scand.
137:
513-520,
1989[ISI][Medline].
39.
Mack, G. W.,
S. Xiangrong,
H. Nose,
A. Tripathi,
and
E. R. Nadel.
Diminished baroreflex control of forearm vascular resistance in physically fit humans.
J. Appl. Physiol.
63:
105-110,
1987
40.
Mader, S. L.
Aging and postural hypotension.
J. Am. Geriatr. Soc.
37:
129-137,
1989[ISI][Medline].
41.
Maspers, M.,
and
J. Björnberg.
2-adrenergic attenuation of capillary pressure autoregulation during haemorrhagic hypotension, a mechanism promoting transcapillary fluid absorption in skeletal muscle.
Acta Physiol. Scand.
142:
470-475,
1991.
42.
Mellander, S.
Comparative studies of the adrenergic neuro-humoral control of resistance and capacitance blood vessels in the cat.
Acta Physiol. Scand.
50, Suppl. 176:
1-86,
1960[Medline].
43.
Mörlin, C.,
B. G. Wallin,
and
B. M. Eriksson.
Muscle sympathetic activity and plasma noradrenaline in normotensive and hypertensive man.
Acta Physiol. Scand.
119:
117-121,
1983[ISI][Medline].
44.
Nielsen, H.,
J. M. Hasenkam,
H. K. Pilegaard,
C. Aalkjaer,
and
F. V. Mortensen.
Age-dependent changes in -adrenoceptor-mediated contractility of isolated human resistance arteries.
Am. J. Physiol. Heart Circ. Physiol.
263:
H1190-H1196,
1992
45.
Öberg, B.
The relationship between active constriction and passive recoil of the veins at various distending pressures.
Acta Physiol. Scand.
71:
233-247,
1967[ISI][Medline].
46.
Olsen, H.,
and
T. Länne.
Reduced venous compliance in the lower limbs of aging humans and its importance for capacitance function.
Am. J. Physiol. Heart Circ. Physiol.
275:
H878-H886,
1998
47.
Rajagopalan, B.,
C. D. Bertram,
T. Stallard,
and
G. Lee.
Blood flow in pulmonary veins. III. Simultaneous measurements of their dimensions, intravascular pressure and flow.
Cardiovasc. Res.
13:
684-692,
1979[ISI][Medline].
48.
Rothe, C. F.
Reflex control of the veins in cardiovascular function.
Physiologist
22:
28-35,
1979[Medline].
49.
Rothe, C. F.
Venous system: physiology of the capacitance vessels.
In: Handbook of Physiology. The Cardiovascular System. Peripheral Circulation and Organ Blood Flow. Bethesda, MD: Am. Physiol. Soc, 1983, sect. 2, vol. III, pt. 1, chapt. 13, p. 397-452.
50.
Schnizer, W.,
J. Klatt,
H. Baeker,
and
H. Rieckert.
Comparison of scintigraphic and plethysmographic measurements for determination of capillary filtration coefficient in human limbs.
Basic Res. Cardiol.
73:
77-84,
1978[ISI][Medline].
51.
Sejersted, O. M.,
A. R. Hargens,
K. R. Kardel,
P. Blom,
O. Jensen,
and
L. Hermansen.
Intramuscular fluid pressure during isometric contraction of human skeletal muscle.
J. Appl. Physiol.
56:
287-295,
1984
52.
Shannon, R. P.,
K. L. Minaker,
and
J. W. Rowe.
The influence of age on water balance in man.
Semin. Nephrol.
4:
346-352,
1984.
53.
Shannon, R. P.,
J. Y. Wei,
R. M. Rosa,
F. H. Epstein,
and
J. W. Rowe.
The effect of age and sodium depletion on cardiovascular response to orthostasis.
Hypertension
8:
438-443,
1986
54.
Smith, J. J.,
D. L. Hudson,
and
P. B. Raven.
Effect of muscle tension on the cardiovascular responses to lower body negative pressure in man.
Med. Sci. Sports Exerc.
19:
436-442,
1987[ISI][Medline].
55.
Sowers, J. R.,
L. Whitfield,
R. Catania,
N. Stern,
M. L. Tuck,
L. Dornfield,
and
M. Maxwell.
Role of the sympathetic nervous system in blood pressure maintenance on obesity.
J. Clin. Endocrinol. Metab.
54:
1181-1186,
1982[Abstract].
56.
Stratton, J. R.,
M. D. Cerqueira,
R. S. Schwartz,
W. C. Levy,
R. C. Veith,
S. E. Kahn,
and
I. B. Abrass.
Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men.
Circulation
86:
504-512,
1992
57.
Sugiyama, Y.,
T. Matsukawa,
A. S. M. Shamsuzzaman,
H. Okada,
T. Watanabe,
and
T. Mano.
Delayed and diminished pressor response to muscle sympathetic nerve activity in the elderly.
J. Appl. Physiol.
80:
869-875,
1996
58.
Taylor, J. A.,
G. A. Hand,
D. G. Johnson,
and
D. R. Seals.
Sympathoadrenal-circulatory regulation of arterial pressure during orthostatic stress in young and older men.
Am. J. Physiol. Regulatory Integrative Comp. Physiol.
263:
R1147-R1155,
1992
59.
Taylor, J. A.,
J. Hayano,
and
D. R. Seals.
Lesser vagal withdrawal during isometric exercise with age.
J. Appl. Physiol.
79:
805-811,
1995
60.
Van Brummelen, P.,
F. R. Buhler,
W. Kiowski,
and
F. W. Aman.
Age-related decrease in cardiac and peripheral vascular responsiveness to isoprenaline: studies in normal subjects.
Clin. Sci. (Colch.)
60:
571-577,
1981[Medline].
61.
Vargas, E.,
and
M. Lye.
Physiological responses to postural change in young and old healthy individuals.
Exp. Gerontol.
17:
445-452,
1982[ISI][Medline].
62.
Wesly, R.,
R. Vaishnav,
J. Fuchs,
D. Patel,
and
J. Greenfield, Jr.
Static linear and nonlinear elastic properties of normal and arterialized venous tissue in dog and man.
Circ. Res.
37:
509-520,
1975
63.
White, M.,
and
F. H. H. Leenen.
Aging and cardiovascular responsiveness to beta-agonist in humans: role of changes in beta-receptor responses versus baroreflex activity.
Clin. Pharmacol. Ther.
56:
543-553,
1994
) and old (
) subjects.
Compliance increased significantly both in young
(P < 0.0001) and old
(P < 0.005) subjects during a
decrease in transmural pressure gradient (arrows). In young subjects,
increase was nonlinear and much more apparent at low transmural
pressures than in old subjects (P < 0.0001). Vertical bars denote SE. For comparison, earlier published
values (