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Noll Physiological Research Center, The Pennsylvania State University, University Park, Pennsylvania 16802-6900
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ABSTRACT |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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During upright tilting, blood is translocated to the dependent
veins of the legs and compensatory circulatory adjustments are
necessary to maintain arterial pressure. For examination of the effect
of age on these responses, seven young (23 ± 1 yr) and seven older
(70 ± 3 yr) men were head-up tilted to 60° in a thermoneutral
condition and during passive heating with water-perfused suits.
Measurements included heart rate (HR), cardiac output
(
c; acetylene
rebreathing technique), central venous pressure (CVP), blood pressures,
forearm blood flow (venous occlusion plethysmography), splanchnic and
renal blood flows (indocyanine green and p-aminohippurate clearance), and esophageal and mean skin temperatures. In response to
tilting in the thermoneutral condition, CVP and stroke volume decreased
to a greater extent in the young men, but HR increased more, such that
the fall in c
was similar between the two groups in the upright posture. The rise in
splanchnic vascular resistance (SVR) was greater in the older men, but
the young men increased forearm vascular resistance (FVR) to a greater
extent than the older men. The fall in
c during
combined heat stress and tilting was greater in the young compared with
older men. Only four of the young men versus six of the older men were
able to finish the second tilt without becoming presyncopal. In
summary, the older men relied on a greater increase in SVR to
compensate for a reduced ability to constrict the skin and muscle
circulations (as determined by changes in FVR) during head-up tilting.
aging; splanchnic vascular resistance; renal vascular resistance; gravity; orthostatic challenge
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INTRODUCTION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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ON ASSUMPTION OF the upright posture, pooling of blood
in the legs decreases venous return to the heart, effectively lowering stroke volume (SV). Orthostatic tachycardia mediated by arterial baroreceptor unloading limits the fall in cardiac output
(c). Total
peripheral vascular resistance (TPR) is also increased to maintain mean
arterial blood pressure (MAP), primarily through vasoconstriction of
muscle, renal, splanchnic, and skin vascular beds (19, 27).
Numerous investigations have compared the hemodynamic responses to
tilting in young and older subjects (11, 19, 30, 31). Even when factors
that often are associated with aging, such as decreased activity level,
increased resting blood pressure (BP), obesity, and the presence of
cardiovascular disease, are controlled, age-related differences in
autonomic-circulatory control are still evident. A blunted heart rate
(HR) response and a smaller increase in muscle and cutaneous resistance
are commonly reported (11, 30, 31). However, decreases in SV and
c during
an orthostatic challenge are less in older individuals (11, 30, 31),
although the exact mechanism for this difference has not been
determined. It has been suggested that the stiffness of arterial and
venous blood vessels is greater in older individuals, blunting venous
pooling and the drop in SV and
c in the upright
posture (35). In addition, it is possible that an augmented increase in
splanchnic vascular resistance (SVR) could partially account for these
observations by its effects on TPR and translocation of blood from the
compliant hepatic circulation.
Rowell and colleagues (25) examined the effect of lower body negative pressure (LBNP) on the control of splanchnic vasoconstriction, determined that the rise in SVR accounted for approximately one-third of the rise in TPR, and estimated that the parallel increase in muscle and cutaneous vascular resistance could also account for one-third of the rise in TPR. Despite the numerous studies investigating an effect of age on the hemodynamic responses to an orthostatic challenge, there have not been any studies that have examined how chronological age may alter the control of the splanchnic circulation during tilting.
In a series of studies, we previously investigated the influence of age on the splanchnic circulation. When young and older groups of men exercised in a warm environment, the older men responded with an attenuated decrease in splanchnic and renal blood flows (15), a difference that was not observed in a thermoneutral condition at the same exercise intensity. It was subsequently shown in a second study that this difference in the heat was unaffected by endurance exercise training in older men (10). In addition, we recently reported that older men redistribute less blood flow from the splanchnic and renal circulations during direct passive heating to the limits of thermal tolerance (21). In short, differences in splanchnic vasoconstriction with age are only apparent during heat stress. These studies illustrate the close relationship between visceral vasoconstriction and cutaneous vasodilation in a warm environment. Passive heating results in a peripheral distribution of blood volume (BV) and may differentially affect splanchnic vasoconstriction in older compared with younger men during an orthostatic challenge. Therefore, in addition to comparing the hemodynamic adjustments to upright tilting, we investigated how passive heating during tilting might modify these responses. Thus passive heating provides a greater stress to blood pressure (BP) maintenance to better elucidate an effect of aging during an orthostatic challenge.
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MATERIALS AND METHODS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Subjects
All procedures used in this investigation were approved in advance by the Committee for the Protection of Human Subjects of the Office of Regulatory Compliance of The Pennsylvania State University. After approved informed consent procedures, seven young (19-28 yr old) and seven older (64-81 yr old) men were recruited to participate in the study. Experiments were carried out during the late fall and winter months in Pennsylvania (November to March); therefore, we considered all subjects unacclimatized to heat, avoiding the potentially confounding effects of acclimatization on their responses to the heat stress.Before participating in the experimental protocol, each subject underwent a screening procedure that included the following: 1) a physical exam by a physician, 2) measurement of skin folds as an estimate of adiposity (1), 3) a resting 12-lead electrocardiogram (ECG), 4) blood tests to establish that hepatic and renal function were normal, 5) measurement of supine, seated, and standing BP, and 6) a maximal graded exercise test on a treadmill with a 12-lead ECG and BP measurements. All subjects were healthy nonsmokers who were not currently taking any medications. Subject characteristics are presented in Table 1.
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Experimental Procedures
On the day of an experiment, subjects reported to the laboratory in a fasted state at 0700. Subjects were weighed before and after the experimental protocol on a scale accurate to ±10 g, and pre- to postexperiment weight loss was <0.5 kg. A 20-gauge peripherally inserted central catheter (PICC; model no. 71956, SoloPICC catheter, SoloPak) had been inserted by a cardiologist a few days before the experiment in either the basilic or cephalic vein of the right arm and advanced into the superior vena cava to the level of the third or fourth intercostal space. Placement of the PICC was verified by a chest X-ray, and adjustment to the placement was made if necessary, followed by a second X-ray. The PICC was connected to a pressure transducer (model no. 42647-05, Transpac IV, Abbott Laboratories, Chicago, IL) and taped to the subject in a plane delineated by a line drawn through the catheter tip (as determined from the X-ray) and the midaxillary line. The transducer was calibrated before and after the experiment using a water manometer. A second catheter was inserted into a forearm or hand vein of the right arm for infusion of a solution containing indocyanine green (ICG; Becton-Dickinson, Rutherford, NJ) and p-aminohippurate (PAH; Merck) for the measurement of splanchnic blood flow (SBF) and renal blood flow (RBF). A third catheter was inserted into the antecubital vein of the left arm for venous sampling. After instrumentation (described below) was completed, subjects were dressed in a water-perfused suit and a plastic coverall to inhibit evaporative cooling. Subjects wore only thin shorts under the water-perfused suit, which covered the entire surface of the body with the exception of the head, feet, and arms below the elbow. The subjects were placed on the tilt table in the supine position with their feet flat against the footboard. Thermoneutral water (~34°C) was then circulated through the suit to keep the subject from becoming overheated during the remainder of the set-up procedure. The baseline period consisted of 50 min during which thermoneutral water from a water bath was circulated through the water-perfused suit. At the end of the baseline period, the first 60° head-up tilt was performed for 20 min. Subjects were raised passively from the supine position to the upright posture in 3-5 s using a hydraulically driven tilt table (model no. OT-9003, Omni Technologies). The subjects were then returned to the supine position for a second baseline period of 10 min. After the second baseline period, warm water (41°C) was circulated through the water-perfused suit for 30 min (heating period), followed by the second 60°C head-up tilt for 20 min or until the subject showed signs of syncope. The subjects were then rapidly cooled by circulating cool water (~20°C) until they recovered.Measurements
Esophageal temperature (Tes), mean skin temperature
sk),
HR (from a 3-lead ECG), and central venous pressure (CVP) (via the
PICC) were measured continuously throughout the entire protocol. Other
data were collected at 10-min intervals during the baseline period and
every 5 min during the two tilts and second baseline and heating
periods. A 7-ml venous blood draw and the measurement of
c were made
simultaneously, followed by BP and forearm blood flow (FBF)
measurements. Pilot work determined that this sequence of data
collection allowed sufficient time after BP and FBF measurements for
ICG and PAH concentrations at the sampling site to be in equilibrium with the rest of the circulation.
Temperatures.
sk was
calculated as the electronic average of eight copper-constantan
thermocouples placed on the upper and lower chest, upper and lower
back, stomach, shoulder, thigh, and calf.
Tes was measured at the level of
the right atrium from a thermistor located in the lumen of a sealed
pediatric feeding tube. During placement, subjects drank 5 ml/kg body wt of water to ensure that they were adequately hydrated
before the experimental procedures. The fluid was ingested ~1.5 h
before the start of the experiment.
FBF.
Two BP cuffs and a mercury-in-Silastic strain gauge were placed on the
left arm for venous occlusion plethysmography (39). Each FBF
determination comprised the average slope of three or more separate
measurements. The upper BP cuff was also used for the measurement of
systolic BP (SBP) and diastolic BP (DBP) by brachial auscultation. MAP
was calculated as (0.33 · SBP) + (0.67 · DBP). Forearm vascular
resistance (FVR) was calculated from the ratio of (MAP 
CVP)/FBF.
c.
c was
determined by an acetylene rebreathing technique (28, 34) using a mass
spectrometer to measure gas concentrations. SV was calculated as
c divided by
HR. Total peripheral resistance (TPR) was calculated as (MAP CVP/
c).
SBF and RBF. For measurement of SBF without catheterization of the hepatic vein, an estimate of the resting extraction ratio (ER) for ICG is needed. Studies using younger subjects have assumed a dye extraction of 0.85 (7). However, the individual hepatic extraction of dyes can vary among subjects and presents a potential source of error, particularly among subjects of differing ages (3). We measured the ER in each subject by an intravenous bolus injection technique based on a two-compartment model of ICG removal from the plasma by the liver (8). This procedure was performed on a separate day after subject screening and at least 5 days before the experimental protocol. Subjects were supine for a minimum of 30 min before withdrawal of an aliquot of blood to serve as a spectrophotometer blank and the bolus injection of 0.5 mg/kg body wt ICG. Five minutes after injection, a 5-ml venous sample was collected in a lithium heparin tube, followed by venous samples every 3 min for 30 min. Samples were centrifuged at 3,000 rpm for 20 min, and the plasma concentration of ICG was measured by spectrophotometry (absorbance of 805 nm and again at 910 nm to test for turbidity). A separate ER was calculated for each subject from the two slopes of the plasma disappearance curve of ICG by computer program (Sigma Plot, San Rafael, CA) using the Marquardt-Levenberg algorithm. In addition, plasma volume (PV) and BV were also measured in nine of the subjects (5 old and 4 young men) on a separate day by Evans blue dye. PV was determined in the remaining five subjects from the extrapolated zero-time concentration of the ICG disappearance curve. The correlation between PV measurements using these two methods has been estimated to be between 85 and 93% (8). Subsequent changes in PV and BV were calculated from the changes in hematocrit (Hct) and hemoglobin measured in triplicate, in accordance with the procedure of Dill and Costill (5).
During the experimental trial, SBF and RBF were determined simultaneously from continuous infusion of ICG and PAH, respectively. These methods and the potential sources of error have been analyzed in detail previously (27, 36) and will only be discussed briefly. After a 20-ml blood draw to serve as a blank, intravenous injection of a priming dose of ICG (0.10 mg/kg body wt) and PAH (8.0 mg/kg body wt) was followed by a constant infusion of 0.5 mg/ml ICG and 12 mg/ml PAH at a rate of 1.0 ml/min. As described above, blood was drawn every 10 min after the start of infusion during the baseline period. To allow for dye equilibration, only the 40- and 50-min samples were used to calculate baseline values. Plasma concentrations of ICG were measured spectrophotometrically (as described above), and plasma concentrations of PAH were determined by colorimetry with the color reagent N-(1-naphthyl)-ethylenediammonium dichloride (2). Although hepatic extraction of ICG remains constant during periods of heat stress (29), SBF changes during passive heating and orthostatic challenges. Corrections for the resulting non-steady-state condition were necessary because the dye removal rate no longer equaled the dye infusion rate. Therefore, splanchnic plasma flow (SPF) was calculated from the rate of change of dye concentration as follows
![SPF = {I − [(C<SUB>a2</SUB> − C<SUB>a1</SUB>)/d<SUB><IT>t</IT></SUB>] ⋅ PV}/(ER ⋅ C<SUB>a</SUB>)](/content/vol276/issue1/fulltext/R203/img003.gif)
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Hct), and SVR was
calculated from the ratio (MAP CVP)/SBF.
Because of the short protocol and the rapid changes in RBF, urine
collection of PAH (preferred method to measure RBF) was not possible in
this study. In the absence of urine collection, a potential source of
error, namely the extrarenal extraction of PAH, becomes a concern.
Furthermore, the same constraints for the measurement of SBF exist for
the measurement of RBF; specifically, the assumption of equality
between excretion rate and infusion rate does not hold as long as
plasma concentration is not constant (36). To overcome these drawbacks,
we made corrections to account for the changes in the plasma
concentration of the solute infused, according to the expression (38)
![RPF = {I − [(C<SUB>a2</SUB> − C<SUB>a1</SUB>)/d<SUB><IT>t</IT></SUB>] ⋅ V<SUB>d</SUB>}/C<SUB>a</SUB>](/content/vol276/issue1/fulltext/R203/img004.gif)
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Hct) and
converted to renal vascular resistance (RVR) as (MAP CVP)/RBF.
This method of determining RBF has proven to be a reliable method for
comparing changes in RBF between young and older men in our lab (10,
15, 17).
Data Analysis
Missing data points. All of the subjects tested were able to complete the first tilt without a significant drop in arterial pressure (>15 mmHg) and without showing signs of presyncope. During the second tilt, however, only four of the seven young subjects were able to complete the full 20-min tilt (young finishers). Two of the young nonfinishers (YNF) completed 15 min of the second tilt, and the remaining YNF only finished 5 min. In contrast, six of the seven older men finished the second tilt, and the one older subject that did not finish the tilt [old nonfinisher (ONF)] completed the first 15 min. The data from the YNF and ONF subjects were included in the statistics performed, and the time points measured after these subjects became hypotensive were treated as missing values. To ensure that the inclusion of data from the subjects who were unable to finish the second tilt did not alter the conclusions of the study, the data were also analyzed with these subjects excluded. The deletion of these data did not affect the results of any of the comparisons despite the reduced power of the statistics; therefore only the analyses including all subjects are presented.
Statistical analyses. Student's t-test was applied to determine the significance of the differences in the subjects' physical characteristics and baseline physiological variables. Two-way (age × time) repeated-measures ANOVA were performed on all variables as a change from the period immediately before each tilt (i.e., baseline 1 and the end of passive heating) to identify the effects of tilting and as a change from baseline 2 to identify the effect of passive heat stress on the variables measured. When significance in the repeated-measures ANOVA was achieved, Student-Newman-Keuls post hoc analyses were performed to locate the differences. The level of significance was set at P < 0.05. All data are presented as means ± SE.
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RESULTS |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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Subject Characteristics
The physical characteristics of the subjects are presented in Table 1. The young and older men differed in age by ~45 yr. The older men were significantly heavier and had a higher percent body fat and a lower maximum O2 consumption
O2 max
(P < 0.05). The two groups did not
differ significantly in height or body surface area. Because we
recruited only normally active subjects (i.e., nonsedentary and
non-endurance trained), all subjects were between the 25th and 75th
percentile rankings for their respective age groups for anthropometric
and O2 max values.
Although there was no significant difference observed in the measured
PV, the older men had a lower calculated BV
(P < 0.05), due in part to their
lower measured Hct values (young, 42 ± 1%; old, 37 ± 2%; P < 0.05).
Physiological Variables at Baseline Periods
There were no baseline temperature differences observed between the two groups of men.c
was significantly lower at baseline in the older men (young, 6.7 ± 0.2 l/min; old, 5.6 ± 0.2 l/min; P < 0.05), due to a lower resting SV (young, 113 ± 7 ml/beat; old,
89 ± 6 ml/beat; P < 0.05) and
despite no differences observed for HR or CVP. Baseline values for FVR
and SVR were similar between the two groups, although resting RVR was
significantly higher in the older men [young, 64 ± 7 resistance units
(mmHg · min · ml
1);
old, 86 ± 4 resistance units; P < 0.05) most likely due to a lower RBF, because no differences in MAP
were observed. TPR was also higher in the older men (young, 13 ± 1 resistance units; old, 18 ± 1 resistance units;
P < 0.05), as was resting SBP,
although significance was not achieved for pulse pressure (PP) or DBP
(P < 0.10 for both variables).
Tilt and Passive Heating Effects
The within-group differences during heating and tilting are presented in Table 2. The data were averaged for the last 10 min of each of the following periods: baseline 1, tilt 1, the end of passive heating, and tilt 2. During thermoneutral tilting, HR increased in both groups but CVP and SV decreased such that a significant fall inc was observed
after the change to an upright posture in the young and older groups of
men (P < 0.05). Increases in SVR and
RVR were also observed in both groups of men, resulting from
significant decreases in splanchnic and renal blood flows and no change
in MAP. In the young men, FVR increased and FBF decreased significantly
during both tilts; however, no differences were observed for these
variables in the older men. All variables measured returned to baseline
levels after the first tilt because there were no within-group
differences observed between the two baseline measurements for either
subject group.
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Passive heating resulted in significant increases in HR, SVR, RVR, and
FBF and significant decreases in CVP, FVR, SBF, and RBF in both groups
of men. A significant increase in
c with heating
was observed in the young but not the older men. Passive heating did
not alter MAP in either group. The combined heat and tilt resulted in
changes similar to those observed during the thermoneutral tilt;
however, the magnitude of changes during tilting differed in some
variables as an effect of the heat stress. The fall in
c during the
second tilt was greater in the young men, primarily due to a larger
fall in SV and despite a greater increase in HR than those observed in
the first tilt. In the older men, HR increased more during the second
tilt but the decline in SV and
c did not differ
between the two tilts.
Age Effects
The average group responses and SE for the variables measured during the experimental protocol are displayed versus time and phase of the experiment in Figs. 1-4. Because it was necessary to allow for ICG and PAH equilibration in the blood after the start of infusion, only the last two baseline measurements (i.e., at 40 and 50 min of baseline) are presented. The asterisks above the time points represent a significant difference during tilting from the young men and take into account differences in the pretilt values (i.e., a change from baseline 1 for tilt 1 or the end of heating for tilt 2). Delta represents a main effect of age throughout the protocol (i.e., a difference in young and older men at all time points).Temperature responses.
Because the water-perfused suit is designed to tightly
control skin temperature and the subjects were unable to dissipate much
heat through sweating due to the plastic coverall, there were no
differences observed between the groups of men for
sk throughout the entire protocol (Fig. 1).
There were also no differences observed in
Tes during any phase of the
experiment. Therefore, the calculated mean body temperature (data not
shown) also did not differ between the two groups. As expected, both
temperature variables were significantly higher during the heating
period (P < 0.05).
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Cardiac responses.
c and SV were
significantly lower in the older men throughout all phases of the
experiment (Fig. 2). There was no
difference observed for
c during the
first tilt, although the older men had a smaller increase in HR (young,
14 ± 3 beats/min; old, 8 ± 4 beats/min;
P < 0.05) and less of a fall in CVP
(young, 4.0 ± 0.6 mmHg; old, 2.3 ± 0.6 mmHg;
P < 0.05) and SV (young, 51 ± 5 ml/min; old, 39 ± 5 ml/min;
P < 0.05). Passive heating caused the young men to have a significantly higher
c
during the last 10 min of heating, due in part to their maintenance of
SV at baseline values despite a fall in CVP. A greater chronotropic
response to tilting during the first 15 min (young, 30 ± 5 beats/min; old, 20 ± 4 beats/min;
P < 0.05) and a greater fall in SV
(57 ± 8 ml/beat; 30 ± 6 ml/beat;
P < 0.05) and CVP (young, 2.9 ± 0.5 mmHg; old, 2.0 ± 0.6 mmHg;
P < 0.05) in the young men was also observed, compared with the older men in the combined heat and tilt,
such that the fall in
c during the
second tilt was significantly greater in the young men (young,
2.4 ± 0.4 l/min; old, 1.2 ± 0.2 l/min;
P < 0.05).
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Vascular resistance responses. RVR and TPR were significantly higher in the older men throughout all phases of the experiment (Fig. 3). In the thermoneutral condition, a greater increase in FVR was observed by 10 min of tilting in the young compared with older men (young, 10.5 ± 2.8 resistance units; old, 3.5 ± 3.2 resistance units; P < 0.05). However, the increase in SVR from baseline 1 was greater in the older men during the first 5 min of the tilt (young, 28.0 ± 4.7 resistance units; old, 40.3 ± 7.2 resistance units; P < 0.05). No differences were observed between the two groups of men during the passive heat stress for the first 20 min. By the end of the heat stress, FVR was significantly lower in the young compared with the older men (young, 7.5 ± 1.6 resistance units; old, 12.8 ± 4.0 resistance units; P < 0.05). Consistent with the thermoneutral condition, tilting during heat stress resulted in greater increases in the young men, but only for the first 10 min of tilting. A greater increase in SVR for the first 10 min was observed in the older men (young, 24.1 ± 10.7 resistance units; old, 55 ± 11.3 resistance units; P < 0.05).
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Pressure responses. SBP, DBP, and MAP were significantly higher in the older men throughout the protocol (P < 0.05) (Fig. 4). However, arterial pressures were well maintained throughout the protocol in both groups of men, and no age differences in response to tilting or heat stress were observed.
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DISCUSSION |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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The major finding in our study was that the older men increased vasoconstriction of the splanchnic vascular bed to a greater extent than the young men during 60° upright tilting in thermoneutral and directly heated conditions. This augmented rise in SVR compensated for a lesser ability of the older men to increase FVR, such that MAP was maintained as well or better than in the young men, particularly when the tilt was combined with heat stress.
There is a large body of evidence that age-related changes in autonomic
control may alter the mechanisms by which responses to an orthostatic
challenge occur. Many (11, 30, 31), but not all (33) studies agree that
the rise in FVR, used to represent changes in resistance of the muscle
and skin circulations, is attenuated during an orthostatic challenge as
an effect of healthy aging but that tolerance to an orthostatic stress
is not compromised. Furthermore, it has been shown in numerous
investigations and is confirmed in the present study that the
orthostatic challenge-induced reflex increase in chronotropic function
is blunted ~10% in older subjects (11, 30, 31, 33). With 44% less
of an increase in FVR by the end of the tilt, the older men must have
increased vascular resistance either by constricting another
circulation to a greater extent or by having less of a fall in
c than the young
men if MAP was to be maintained. Although
c and SV were lower in our older subjects throughout the protocol, SV decreased 14 mmHg more from baseline during tilting in the young subjects, such that
the fall in c
with the assumption of the upright posture was only slightly (not
significantly) less in the older subjects. In this construct, the
remaining regional circulations capable of significantly altering TPR
are the renal and splanchnic circulations. RVR was higher in the older
men, consistent with the age-related reduction in RBF (17, 37), but the
increase in RVR was similar between the groups and thereby could not
account for the maintenance of MAP. Therefore, the 8% greater increase
in SVR observed in the older men is consistent with the requisite
changes in systemic hemodynamics to partially account for the
maintenance of BP.
The contrariety of the reflex hemodynamic responses in the young and
older men to tilting may reflect differences in the stimulation applied
to the baroreceptors. Previous studies using acute and chronic levels
of LBNP sufficient to lower CVP without affecting MAP or PP have
suggested that the increase in FVR is primarily influenced by the
cardiopulmonary baroreceptors and that the increase in SVR is under the
dual control of the arterial and cardiopulmonary baroreceptor
populations (9, 13). In our study, CVP fell 1.7 mmHg more in the young
men than in the older men during the assumption of the upright posture,
suggesting less of a stimulus to the cardiopulmonary baroreceptors in
the older men. This may partially explain the attenuated increase in
FVR in the older subjects. It is important to note that a more recent
study has shown that low levels of LBNP alter aortic distention,
suggesting that the arterial baroreceptors may also affect FVR (32).
However, the change in PP was similar between the two groups of men in the first tilt. In this context, the stimulus to increase FVR was not
greater in the young men. Furthermore, this suggests that the lower
reflex tachycardia in the older men could not be explained by the
lesser removal of the inhibitory influence of this baroreceptor population on chronotropic function (13). It is more likely that a
reduced 
-receptor responsiveness with aging (18) may have resulted
in the attenuated HR response in the older men. Therefore, the larger
increase in SVR in the older men cannot be explained on the basis of
the CVP and PP responses described above. It is plausible that the
older men have adapted to the stress of maintaining an upright posture
with an augmented splanchnic vasoconstrictor response for a given
change in CVP or PP to compensate for a reduced ability to increase
resistance in the muscle and skin circulations.
It has also been reported that the shift in thoracic BV during orthostasis, measured using transthoracic impedance, is less in older men, contributing to less of a reduction in SV (6, 31). This was surprising because these investigators reported less sequestration of blood from the periphery with age but similar increases in leg BV in young and older subjects during tilting. If the increase in leg BV is similar during orthostasis and the total volume of blood available is less in older men, then a greater fall in central BV would be expected, because a larger proportion of the BV would be in the dependent veins on assumption of the upright posture. A subsequent study reported no difference in the transthoracic shift of BV but still reported that SV fell less in the older subjects (33). An augmented left ventricular contractility was suggested as a potential mechanism to explain this phenomenon. However, this rationale does not seem likely, because others have reported a relative inability of elderly subjects to reduce end-systolic volume during a 60° head-up tilt (29). Therefore, an alternative hypothesis supported by the results of the present study suggests that greater splanchnic vasoconstriction caused more blood to be shifted from the compliant hepatic circulation in the older men, serving to limit the fall in CVP, filling pressure, and, in turn, SV. However, it is unlikely that the ~8% greater increase in SVR in the older men could account for all the difference observed in CVP and SV. The trend toward a higher mean and diastolic pressure in our older subjects suggests that stiffening of the arterial tree is evident. The smaller reduction in CVP and SV in the older men supports the concept that this has also occurred on the venous side, although no direct evidence is available in the present study.
The additional stress imposed by passive heating during the second tilt
was designed to explore further the hemodynamic responses to tilting by
providing a more severe challenge to the maintenance of BP. In the
present study, the heat stress was designed to result in similar
increases in
sk and
Tes in the two groups of men. The
responses to the heat stress were very similar between the two groups,
with the notable exceptions of a greater decline in FVR in the young
men [due to a larger increase in skin blood flow (SkBF)] and an increase in
c, a response
not observed in the older men. Rowell and colleagues (23, 26) have
previously described the existence of an inotropic response to an
elevation in skin temperature before a significant increase in core
temperature is observed; however, recent work in our lab (21) suggests
that this response may be diminished in older individuals, which may explain this difference. Quantitatively, the other responses to the
heat stress were similar between the groups.
It is interesting to note that SVR was higher in both groups of men
during the second tilt, providing evidence that both groups of men had
a reserve of splanchnic vasoconstriction during thermoneutral tilting
that aided in maintaining MAP when heat stress was combined with
orthostasis. However, the greater increase in SVR and less of a fall in
CVP in the older men was only evident for the first 10 min when they
were tilted in the heated condition. Although we have previously shown
that older men do not redistribute as much blood flow from the
splanchnic circulation during exercise in the heat (10) or direct
passive heating (21), older men appear to redistribute as much flow
from the splanchnic region as the young men during an upright tilt in
the heat. Taken together, these data suggest that splanchnic
vasoconstriction is not compromised with advanced age, but that a tight
coupling of the highly compliant cutaneous and splanchnic circulations
exist. Therefore, the higher SkBF in the young men during heat stress
or exercise (10, 21) provides a greater stimulus for splanchnic
vasoconstriction. The high SkBF and translocation of blood to the more
compliant dependent veins with heating in the upright position in the
young men, however, appears to decrease venous return to such an extent
that CVP, SV, and
c are
compromised even with relatively mild levels of heat stress.
The greater decline in SV in the young subjects during the tilt in the heated condition may have resulted from greater pooling of blood in the cutaneous veins that is consistent with a larger increase in SkBF for a given rise in skin and core temperatures (14, 16). Although it has been shown that during direct passive heating skin retains the ability to vasoconstrict in response to LBNP and tilting, the vasoconstriction does not completely override heat-induced vasodilation (12, 13). It is not known why the young subjects who were unable to finish the second tilt did not increase SVR to an even greater extent to maintain pressure. It is possible that the maximal amount of vasoconstriction under these conditions had occurred. Alternatively, it is possible that the clearance technique used to measure SBF was not reliable during the period of severe hypotension, most likely affecting ER, such that an accurate measurement of SVR in the subjects at that time was not possible.
In summary, we compared the complex hemodynamic responses to upright
tilt in young and older men in thermoneutral and passively heated
conditions. The compensatory mechanisms of the cardiovascular system to
maintain MAP during orthostasis differed as an effect of age. The young
men relied on a greater increase in resistance of the muscle and
cutaneous circulations to overcome a greater fall in CVP and SV. The
older men relied on a greater increase in SVR to compensate for a
reduced ability to increase muscle and skin vascular resistance. With
the addition of heat stress, c in the young
men was increased so that on the assumption of the upright posture, the
decline in c was
greater than in the older men.
Perspectives
The greater decreases in CVP and SV during tilting in young men suggest that there is more pooling of blood in the dependent veins compared with older men. The greater splanchnic vasoconstriction in older men during tilting in the thermoneutral condition may contribute to the better maintenance of CVP and SV but does not account for all of the differences observed. This provides evidence that venous pooling of blood in older individuals is less and is most likely due to reduced venous compliance, although more direct studies are needed. The higher SkBF in young subjects for a given level of heat stress appears to make them more susceptible to orthostatic intolerance in the heat than healthy older subjects. However, a greater reliance of older individuals to increase SVR to maintain MAP during an orthostatic challenge, as suggested in the present investigation, may partially explain the incidence of orthostatic intolerance associated with factors that affect the ability to constrict this circulation. Excessive splanchnic blood pooling appears to be an important initial event in the development of postprandial hypotension and unexplained syncope. Furthermore, certain vasoactive medications could have profound effects on the ability to maintain MAP during an orthostatic challenge if they effectively limit the ability to increase SVR. Because older subjects do not appear to be able to increase FVR to the extent observed in the young subjects, a reduced ability to increase SVR could have detrimental effects on MAP on standing in certain patient populations.| |
ACKNOWLEDGEMENTS |
|---|
The valiant effort by the subjects is greatly appreciated. The authors also appreciate the assistance of Jane Pierzga, Carla Thomas, Esther Brooks, and Bill Farquhar and the scientific input of Dr. E. R. Buskirk and Dr. T. R. McConnell. The authors further thank Beckton-Dickinson for supplying the ICG and Merck Pharmaceuticals for supplying the PAH. The nursing care provided by the staff of the General Clinical Research Center at the Noll Physiological Research Laboratory is appreciated.
| |
FOOTNOTES |
|---|
This study was supported by National Institute on Aging Grant R01-AG-07004-09, American College of Sports Medicine Foundation Grant for Doctoral Students, and National Aeronautics and Space Administration Grant NAGW-4839 and also by National Institutes of Health Grant M01-RR-10732. S. L. Wladkowski was supported by National Institute of General Medical Sciences predoctoral training Grant T32-GM-08619.
Address for reprint requests: C. T. Minson, Dept. of Anesthesia Research, Mayo Clinic and Foundation, Rochester, MN 55905.
Received 30 October 1997; accepted in final form 24 September 1998.
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REFERENCES |
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Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
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, significant
difference between 2 groups below bracket (i.e., throughout
protocol).
