| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Vol. 84, Issue 4, 1323-1332, April 1998
Noll Physiological Research Center, Pennsylvania State University, University Park, Pennsylvania 16802-6900
 |
ABSTRACT |
|---|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
During
direct passive heating in young men, a dramatic increase in skin blood
flow is achieved by a rise in cardiac output (
c) and
redistribution of flow from the splanchnic and renal vascular beds. To
examine the effect of age on these responses, seven young (Y; 23 ± 1 yr) and seven older (O; 70 ± 3 yr) men were passively heated with
water-perfused suits to their individual limit of thermal tolerance.
Measurements included heart rate (HR), c (by
acetylene rebreathing), central venous pressure (via peripherally inserted central catheter), blood pressures (by brachial auscultation), skin blood flow (from increases in forearm blood flow by venous occlusion plethysmography), splanchnic blood flow (by indocyanine green clearance), renal blood flow (by
p-aminohippurate
clearance), and esophageal and mean skin temperatures.
c was
significantly lower in the older than in the young men (11.1 ± 0.7 and 7.4 ± 0.2 l/min in Y and O, respectively, at the limit of
thermal tolerance; P < 0.05),
despite similar increases in esophageal and mean skin temperatures and
time to reach the limit of thermal tolerance. A lower stroke volume (99 ± 7 and 68 ± 4 ml/beat in Y and O, respectively, P < 0.05), most likely due to an
attenuated increase in inotropic function during heating, was the
primary factor for the lower c observed in
the older men. Increases in HR were similar in the young and older men;
however, when expressed as a percentage of maximal HR, the older men
relied on a greater proportion of their chronotropic reserve to obtain
the same HR response (62 ± 3 and 75 ± 4% maximal HR in Y and
O, respectively, P < 0.05). Furthermore, the older men redistributed less blood flow from the
combined splanchnic and renal circulations at the limit of thermal
tolerance (960 ± 80 and 720 ± 100 ml/min in Y and O,
respectively, P < 0.05). As a result
of these combined attenuated responses, the older men had a
significantly lower increase in total blood flow directed to the skin.
aging; hyperthermia; cardiac output; skin blood flow; cardiovascular responses
| |
INTRODUCTION |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
THE CARDIOVASCULAR adjustments of young men to direct
passive heating were elegantly studied by Rowell and colleagues in the 1960s and early 1970s (24-29). These investigators used invasive measurements to investigate the cardiovascular responses to direct heating of the skin with water-perfused suits (26, 27, 29), heating
subjects to the limits of thermal tolerance to elicit maximal
hemodynamic responses to heat stress (27). Cardiac output (c) in some
subjects more than doubled from baseline to the limit of thermal
tolerance. This dramatic increase in
c was accomplished in the young subjects by an increase in heart rate (HR)
and an increase in, or maintenance of, stroke volume (SV), despite a
fall in central venous pressure (CVP). The increase in SV was therefore
attributed to an increase in sympathetic stimulation primarily
affecting the 
-receptors. In addition, the high skin and
core temperatures resulted in a redistribution of blood flow from the
splanchnic and renal vascular beds, independent of baroreceptor stimulation (29). Using this model to study thermoregulatory control,
Rowell (24) determined that total skin blood flow (SkBF) in young men
could increase up to 7.6 l/min during maximal passive heat stress.
There is evidence that advanced aging may alter the cardiovascular
mechanisms that underlie human thermoregulatory control. It has been
well established that the SkBF response to increasing core temperature
is reduced as a function of age (13, 17) and that the attenuated
response is due to a reduced active vasodilator sensitivity (16) and a
reduced maximal SkBF capacity (22) in aged skin. It is unknown,
however, how control of central hemodynamic function and blood flow to
visceral organs may be affected by aging during direct passive heating.
The reduced -adrenergic responsiveness of the heart in advanced age
may attenuate the chronotropic and inotropic reflex responses to
passive heating. During exercise, when the muscle pump aids venous
return and, therefore, cardiac filling pressure, an age-related
increased reliance on the Frank-Starling mechanism partially
compensates for the reduced adrenergic responsiveness and helps
maintain SV. However, during passive heat stress, blood is pooled in
the cutaneous veins, CVP is reduced, and the increase in
c is not
explained by the Frank-Starling mechanism of the heart (23). Within
this construct, it is reasonable to hypothesize that older individuals would respond to direct passive heating with an altered cardiac profile. Similarly, it is not known whether splanchnic (SBF) and renal
blood flows (RBF) would be reduced to a greater extent during passive
heating in older individuals to compensate for an attenuated c response,
although evidence from studies during exercise suggests that such
compensation is unlikely (10, 15).
Therefore, the purpose of this investigation was to compare the central
and peripheral hemodynamic responses of young and older men during
direct passive heating to the limit of thermal tolerance. Specifically,
it was hypothesized that the older men would have a lower
c at the limit
of thermal tolerance, which would be associated with a lower SkBF.
Furthermore, it was hypothesized that the older men would have an
attenuated contribution of redistributed blood flow from the splanchnic
and renal vascular circulations to the skin.
| |
MATERIALS AND METHODS |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Subjects
All procedures utilized in this investigation were approved in advance by the Committee for the Protection of Human Subjects of the Office of Regulatory Compliance, The Pennsylvania State University. After approved informed consent procedures, seven young (Y; 19- to 28-yr-old) and seven older (O; 64- to 81-yr-old) men were recruited to participate in the study.Before participating in the experimental protocol, each subject underwent a screening procedure that included 1) a physical examination by a physician, 2) measurement of skinfolds as an estimate of adiposity (1), 3) a resting 12-lead electrocardiogram, 4) blood tests to establish that hepatic and renal function were normal, 5) measurement of supine, seated, and standing blood pressure (BP), and 6) a maximal graded exercise test on a treadmill. All subjects were healthy nonsmokers who were not currently taking any medication that had the potential to impact the cardiovascular or thermoregulatory variables of interest. Subject characteristics are presented in Table 1.
|
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 weight loss was kept to within 0.5 kg during the experiment by infusion of normal saline. A 20-gauge peripherally inserted central catheter (PICC; SoloPICC 71956, SoloPak) was inserted in 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 42647-05 Transpac IV, Abbott) and attached to the subject at the intersection of 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) and p-aminohippurate (PAH; Merck) for the measurement of SBF and RBF, respectively. 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 feet were wrapped in plastic to minimize heat loss. The subjects were placed in the supine position, and thermoneutral water (~34°C) was 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 circulating water bath was circulated through the water-perfused suit. At the end of the baseline period, the water in the suit was switched to a second bath with 50°C water. The heating period was continued until the limit of thermal tolerance was reached. The limit of thermal tolerance was defined as the time at which 1) the subject expressed that he was unable to continue, 2) esophageal temperature (Tes) reached 39.5°C, or 3) the subject was unable to control hyperventilation as determined by end-expiratory CO2 concentration. When one of these criteria was attained, the recovery period began and the subject was cooled with cold water (~15°C) from a third water bath for 20 min.
Measurements
Tes, mean skin temperature (
sk),
HR (from a 3-lead electrocardiogram), and 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 heating and recovery periods. Venous blood (7 ml) was
drawn and c
was measured simultaneously, then BP and forearm blood flow (FBF) were
measured. Pilot work in our laboratory 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 unweighted 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 insertion, subjects drank water (5 ml/kg
body wt) to ensure that they were adequately hydrated before the
experimental procedures.
FBF. Two BP cuffs and a mercury-in-Silastic strain gauge were placed on the left arm for venous occlusion plethysmography as described by Whitney (37). Each FBF determination comprised the average slope of three or more separate measurements. Changes in FBF were assumed to reflect changes in forearm SkBF, because underlying inactive muscle blood flow does not change under conditions of heating (6). The upper BP cuff was also used for the measurement of systolic (SBP) and diastolic BP (DBP) by brachial auscultation. Mean arterial pressure (MAP) was calculated as (0.33 · SBP) + (0.67 · DBP).
c.
c was
determined by an acetylene-rebreathing technique (30, 31, 33) utilizing
a mass spectrometer to measure gas concentrations. SV was calculated as
c / HR.
Total peripheral resistance (TPR) was calculated as [(MAP 
CVP)/c].
SBF and RBF. To measure 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 (8); however, individual hepatic extraction of dyes can vary among subjects and presents a potential source of error, particularly among subjects of different ages (4). 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 (9). 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 ICG (0.5 mg/kg body wt). Five minutes after injection, a 5-ml venous sample was collected in a lithium heparin tube, then venous samples were obtained every 3 min for 30 min. Samples were centrifuged at 3,000 rpm for 20 min, and the plasma concentration was measured by spectrophotometry (absorbency 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 (Sigma Plot, San Rafael, CA) utilizing the Marquardt-Levenberg algorithm. In addition, plasma volume (PV) and blood volume (BV) were also measured in nine of the subjects (5 O and 4 Y) on a separate day by Evans blue dye. PV was determined in the remaining five subjects from the extrapolated time 0 concentration of the ICG disappearance curve. The correlation between PV measurements using these two methods has been estimated to be 0.85-0.93 (9). Subsequent changes in PV and BV were calculated from the changes in hematocrit (Hct) and hemoglobin concentration measured in triplicate in accordance with the procedure of Dill and Costill (7).
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 (28, 34) and will only be discussed briefly. After 20 ml of blood were drawn 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 ICG (0.5 mg/ml) and PAH (12 mg/ml) 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 with the color reagent N-(1-naphthyl)-ethylenediammonium dichloride (2). Although hepatic extraction of ICG remains constant during periods of heat stress (28), SBF changes during passive heating. Corrections for the resulting non-steady-state condition were necessary, since 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>a<IT>2</IT></SUB> − C<SUB>a<IT>1</IT></SUB>)/d<IT>t</IT>] · PV}/(ER · C<SUB>a</SUB>)](/content/vol84/issue4/fulltext/1323/img002.gif)
|
Hct)].
Because of the short protocol and the rapid changes in RBF, urine
collection of PAH (the 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 (34). To overcome these
drawbacks, corrections were made to account for the changes in the
plasma concentration of the solute infused according to the following
expression (36)
![RPF = {I − [(C<SUB>a<IT>2</IT></SUB> − C<SUB>a<IT>1</IT></SUB>)/d<IT>t</IT>] · V<SUB>d</SUB>}/C<SUB>a</SUB>](/content/vol84/issue4/fulltext/1323/img003.gif)
|
Hct)]. This method of determining RBF
has proven to be a reliable method for comparing changes in RBF between
young and older men in our laboratory (10, 15).
The acetylene-rebreathing system used in this investigation was
equipped to measure O2 and
CO2 concentrations and minute
ventilation between
c
measurements. This allowed us to monitor the subject's breathing at
given intervals to control for the hyperventilation that is known to
attend heat stress. Subjects were also instructed before the experiment
on how to suppress the anxiety of hyperthermia by nose breathing and
making a concerted effort to relax. Using these techniques, all
subjects were able to maintain a constant end-expiratory
PCO2 throughout most of the heating
period. Three of the young men were not able to control their breathing and began to hyperventilate just before the last measurement. The
resulting hypocapnia may have had a vasomotor effect, causing the
decreases in
c, SV, CVP,
and FBF during the last measurement (at the limit of thermal
tolerance). Hypocapnia is known to cause cutaneous vasoconstriction and
muscle vasodilation (3), which would explain these changes in flow. HR
at this time increased, presumably in an attempt to maintain pressure.
None of the older men hyperventilated during the experiment.
Statistical Analyses
Student's t-test was used to determine significant differences between the subject characteristics. A two-way (age × time) repeated-measures ANOVA was performed on all variables from baseline through the first 60 min of heating. When significance in the repeated-measures ANOVA was achieved, a Student-Newman-Keuls post hoc analysis was performed to determine the time during which the difference between ages occurred. To account for differences in the time to maximal tolerance, each individual's final 20 min of heating was used to calculate a group mean. The group (Y and O) average was then calculated, and a two-way (age × time period, i.e., baseline or end of heating) ANOVA was performed to determine significant differences for the variables between age groups. Paired t-tests were applied at select time points to determine whether significant differences existed between the two trials in subjects who volunteered to repeat the protocol. The level of significance was set at P < 0.05. Values are means ± SE.| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
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 maximal O2 uptake (P < 0.05). The two groups did not differ significantly in height or body surface area (AD). 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 maximal O2 uptake values (14).Although no significant difference was observed in the measured PV when expressed in liters, PV was 23% lower when expressed relative to body weight (ml/kg) in the older men. In addition, the older men had a lower calculated BV (P < 0.05), due in part to their lower measured Hct (42 ± 1 and 37 ± 2% in Y and O, respectively, P < 0.05). Both groups of men lost ~0.6 kg of body weight during the protocol due to sweating (0.7 ± 0.3 and 0.5 ± 0.4 kg in Y and O, respectively), and there was no difference between the groups of men (P > 0.05). Evaporative water loss was minimized by the plastic coverall and by the infusion of ~500 ml of normal saline solution to keep the sampling catheter patent during the entire protocol.
Temperature and Hemodynamic Variables
The average group responses for the variables measured during the experimental protocol are displayed vs. time in Figs. 1-4. To allow for temperature and hemodynamic stabilization and 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.
|
|
|
|
Although there were no age differences in time to maximal tolerance (68 ± 6 and 64 ± 7 min in Y and O, respectively, P > 0.10), the individual tolerance time to direct passive heating varied among subjects (60-80 and 55-85 min in Y and O, respectively). After baseline, responses during the first 60 min of heating are plotted for each variable, followed by the averaged values during the last 20 min of each subject's heating period to account for the differences in tolerance time.
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,
sk was not different between the groups of men at baseline or throughout the
heating protocol (Fig. 1). No differences were observed in Tes at any time period. Therefore,
the calculated mean body temperature likewise did not differ between
the two groups at baseline (36.3 ± 0.4 and 36.0 ± 0.6°C in
Y and O, respectively) or at the limit of thermal tolerance (38.8 ± 1.0 and 38.7 ± 0.8°C in Y and O, respectively).
Cardiac responses.
Baseline values of
c, HR, and SV
did not differ between the young and older men (Fig. 2). During heat
stress, c was
significantly lower in the older men at all time points during the
first 60 min of heating (age × time interaction,
P < 0.05).
c remained significantly lower in the older men during the final 20 min of heating
(P < 0.05). No differences in HR
when expressed as beats per minute were observed between the groups.
When expressed as a percentage of maximal HR, the HR was significantly
higher after 35 min of heating in the older men (62 ± 3 vs. 75 ± 4%). Although the pattern of SV response was different between
the groups, no significant differences in SV were observed during the
first 60 min of heat stress. However, SV was significantly lower during the last 20 min of heating in the older than in the young men (68.3 ± 4.3 vs. 89.8 ± 6.5 ml/beat for final value,
P < 0.05), and in the older men the
final SV was significantly lower than their baseline SV (68.3 ± 4.3 vs. 91.7 ± 5.5 ml/beat, P < 0.05). There were no differences in baseline CVP or 
CVP
during heat stress between the groups at any time.
Other cardiovascular responses.
Baseline FBF and SBF were similar in the older and young men (Fig. 3).
FBF was lower in the older than in the young men at all time points
after 15 min of heating (P < 0.05)
as well as during the final 20 min of heating (8.7 ± 1.4 vs. 14.4 ± 1.6 ml · 100 ml
1 · min1
at 20 min of heating and 18.3 ± 1.8 vs. 28.1 ± 2.0 ml · 100 ml1 · min1
for final value). There were no differences in SBF between the two
groups of men during the heating protocol. There was a significant age
difference in RBF, with a lower flow at baseline in the older men (873 ± 64 vs. 1,137 ± 70 ml/min, P < 0.05) and at all time points during heating (674 ± 26 vs. 847 ± 69 ml/min for final value, P < 0.05); however, there was no difference in the pattern of responses.
When the redistribution of blood flow from the splanchnic and renal
vascular beds is combined (i.e., the combined decrease in SBF and RBF
from baseline to maximal heating), the older men redistributed
significantly less blood flow away from these two circulations than did
the young men (0.96 ± 0.08 vs. 0.72 ± 0.10 l/min,
P < 0.05). Similar to the
differences observed for FBF, the predicted change in flow directed to
the skin (SkBF) from baseline was significantly lower in the older
men at all time points after the first 10 min of heating
(P < 0.05).
Pressure responses. MAP was well maintained throughout the protocol in both groups of men, with no significant differences observed between the groups (Fig. 4). The older men had a higher DBP at baseline and throughout the heating period (P < 0.05), but there were no differences in SBP. There was also a significant effect of age on TPR at all time points (P < 0.05).
The present study is the first to quantify the difference in SkBF between older and young men by comparing the increase in blood flow to the skin by measuringc and
its distribution to the major vascular beds. Figure
5 displays the separate contributions of
c, SBF, and RBF
to the total increase in SkBF from baseline to the end of heating.
The young men increased SkBF by an average of 5.8 l/min compared with
an average increase of only 2.7 l/min by the older men. Although the
calculated increase in SkBF in our young subjects is lower than the 7.6 l/min average increase reported by Rowell (24) and Detry and colleagues
(6), all young subjects were well within their range of 3-11
l/min.
|
Repeatability.
Repeatability tests were performed by two of the young men who
volunteered to repeat the entire protocol and in one older man whose
first test was stopped after 35 min of heating because of logistical
problems. In the two young men, reliability coefficients of
determination
(r2) for the
measurements of
c, SBF, RBF, and
FBF at 60 min of heating were 0.92, 0.86, 0.84, and 0.96, respectively.
In the older man,
r2 for the
variables at 30 min of heating were 0.85, 0.88, 0.79, and 0.94, respectively. Paired t-tests on these
variables at baseline, every 15 min of heating, and at maximal
tolerance did not reveal any significant intrasubject differences
between the first and second tests.
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
The major finding of the present investigation was that the central
cardiovascular responses to direct passive heating were altered in
older compared with young men. Despite this, the tolerance time to
maximal heating was similar. Specifically,
c was
significantly lower in the older than in the young men, despite similar
increases in skin and core temperatures. A lower SV, most likely due to an attenuated increase in inotropic function during the heat stress, was the primary factor for the lower
c observed in
the older men. Increases in HR during the heating protocol were similar in the young and older groups; however, when expressed as a percentage of maximal HR, the older men relied on a greater proportion of their
chronotropic reserve to obtain the same HR response. Furthermore, the
older men redistributed less blood flow from the splanchnic and renal
circulations. As a result of these combined attenuated cardiovascular
responses, total blood flow directed to the skin was significantly
lower in the older men.
Because it has been well established that the SkBF response to
increasing core temperature is decreased as an effect of age (13, 17), it was not surprising that the increase in
c directed to
the skin was lower in the older men during passive heating. For total
SkBF to increase,
c must increase
or a greater proportion of
c must be
diverted from other regions to the cutaneous circulation. During
cycle exercise in the heat, a reduced ability to increase c and to
redistribute blood flow from the splanchnic and renal vascular
circulations has been reported in older subjects (10, 15). It is
plausible that the reduced ability of older men to increase
c and
redistribute blood flow from the visceral circulations (particularly
the renal bed) may not allow SkBF to be increased in older men to the
same extent as in young men during passive heating. However, an
alternate explanation might be that the lower SkBF was consistent with
a matching of c
to the attenuated vasodilator capacity in the aged skin and, therefore,
not limited to any extent by the altered central cardiovascular
function. Indeed, the differences observed in the hemodynamic profiles
of the young and older men are very intriguing. Older individuals
typically respond to an increased cardiac demand, such as during
exercise, with an increased reliance on the Frank-Starling mechanism of
the heart to partially offset the age-related reduction in
-adrenergic responsiveness (21). During resting heat stress,
however, the muscle pump is not active to drive blood centrally.
Therefore, the increase in cutaneous venous pressure and the fall in
CVP attending the rise in SkBF create a large pressure gradient between
the cutaneous veins and the right atrium to aid venous return (25).
Furthermore, because preload is decreased during passive heat stress
(assuming that CVP is an adequate index of ventricular filling under
these experimental conditions), the increase in
c is
not explained by the Frank-Starling mechanism of the heart and may
potentially limit the ability of older individuals to increase
c in these conditions.
SV was increased or maintained in the subjects studied by Rowell et al.
(26, 29) and in the young men in the present study under these
conditions (especially for the first 30-40 min), indicative of an
increase in the contractile force of the heart. This increased inotropic response was not observed in the older men, as SV fell progressively throughout the heating. The older men relied more heavily
on an increase in chronotropic function, so that there was no
difference in HR between the two groups at a given time or
Tes, despite the lower
c in
the older men. This finding that older men are operating at a higher
percentage of their HR reserve may have particular relevance during
climatic heat waves in older individuals with advanced coronary artery
disease in which delivery of O2 to
the myocardium is limited. Those individuals with a reduced coronary
flow would be at a greater risk for cardiac events with a high HR as
skin and core temperatures are elevated in hot, humid conditions.
It is apparent from many investigations (25) that there is no
identifiable absolute CVP at which adaptation to thermal stress becomes
limited. Under the condition of passive heat stress, the heart is
working in the low range of the Frank-Starling curve, where small
decreases in filling pressure can induce a large decrement in
c. Therefore, in
young men the increased sympathetic drive to the heart seems more
important to maintaining SV than ventricular filling (20). In this
scheme, CVP must be allowed to fall to zero to enable venous return to
continue and maintain
c and arterial
pressure (23). In older men the increased sympathetic drive to the
heart may not be sufficient to increase
c because of
decreased -adrenergic receptor responsiveness. Therefore, intrinsic
mechanisms of the heart may play a more important role during heat
stress as individuals age. However, the pressure gradient between the
cutaneous veins and the right atrium presumably was less in the older
men (although this was not measured) because of a lower SkBF and
slightly smaller fall in CVP during heating (P = NS). This may have resulted in a
functional reduction in venous return, leading to a lower filling
pressure and contributing to the inability of the older men to maintain
SV, particularly in light of their increased reliance on the
Frank-Starling mechanism. In addition, as a large proportion of total
BV is sequestered in the cutaneous veins when SkBF is high, the smaller
BV of the older men may have compounded the problem of a reduced venous return.
We previously showed that redistributed blood flow from the splanchnic
and renal circulations is less in older men exercising at 60% of peak
O2 uptake in the heat (10, 15). In
the present study the combined flows from these two circulations, i.e.,
the total redistributed flow from the visceral circulation, were
significantly less in the older men (Fig. 5;
P < 0.05). Rowell and colleagues (29) previously showed that the increase in splanchnic and renal vascular resistance during heat stress was not due to a reduced BP and
postulated that vasoconstriction of the splanchnic and renal vascular
beds arises from a reflex response to the increase in skin and core
temperatures. It is therefore unlikely that the difference observed in
redistributed flow was due to a greater vasoconstrictor stimulus in the
young men and probably reflects a greater end-organ response to
sympathetic outflow. However, the extent to which differences in
visceral vasoconstriction contribute to the total increase in SkBF is
small (~0.25 l/min) compared with the much greater impact of a lower
c (Fig.
6).
|
MAP was maintained fairly well in both groups of subjects, and the transient, small changes in arterial pressure to passive heating were similar to those in the study by Rowell (24). There was a significant age effect on DBP at rest and throughout the heating protocol, although the pattern of response to heat stress was similar. This higher DBP and slightly elevated SBP resulted in a slightly higher MAP. MAP is known to increase mildly with age and is usually attributed to an increase in SBP. The reason for the elevated DBP in the present study is unknown and is not a consistent finding in healthy older normotensive patients, although a great deal of heterogeneity exists (21). TPR fell in the young men by 38% on average, similar to the 29-58% decrease in TPR in the subjects studied by Rowell et al. (29). In the older men, however, TPR decreased only 23% during heating, which is not surprising in light of the lower cutaneous vascular conductance.
Because it was first reported that blood flow to the underlying
musculature does not change during whole body passive heat stress or
local heating of the forearm (6, 11), many investigators have used
venous occlusion plethysmography during heat stress, i.e., changes in
FBF, to represent changes in SkBF. However, questions exist as to
whether this change in SkBF at the forearm is representative of changes
in SkBF in other areas of nonacral skin and whether this method is
equally valid for older individuals. In the present study, FBF was
highly correlated with the SkBF calculated from the combined changes
in c, SBF, and
RBF (r2 = 0.93;
Fig. 6). Although these data do not address whether SkBF measured at
different sites, such as in the calf, in an individual may vary, they
do support the theory that changes in FBF can be used to represent
changes in flow to the skin as a whole, irrespective of age. On the
basis of our findings, the increase in SkBF can be predicted from
the measurement of FBF in this group of subjects by the following
formula: SkBF (l/min) = [0.19 · FBF
(ml · 100 ml1 · min1)] + 0.19.
The slight deviation from a linear relationship between FBF and
SkBF in the young men in Fig. 6 at the lower flow rates may be
explained by a difference in the initial responsiveness of the skin to
local and reflex increases in
sk and
Tes. The site used for the
measurement of FBF by venous occlusion plethysmography was not directly
heated by the water-perfused suit; therefore, an increase in FBF
reflects a purely reflex response to passive heating. SkBF, on the
other hand, reflects an increase in blood flow to the skin due to the
combination of local and reflex responses to the high skin temperature.
A similar relationship between direct and reflex changes in FBF was
observed in young men by Taylor et al. (32), when the authors
simultaneously compared FBF responses to directly heating one forearm
to ~42°C with the reflex increase in FBF in the contralateral,
nonheated arm during whole body heat stress. A more rapid initial
increase in FBF in the directly heated arm was noted; however, in most
of the subjects FBF values in the two arms converged once
Tes had increased by 0.5°C.
These data, combined with the high correlation between FBF and
SkBF in the present study, provide support for the accuracy and
reliability of FBF as an index of changes in SkBF.
It is interesting to note that the more rapid initial increase in
SkBF than in FBF in the young men discussed above was not
observed in the older men, despite the fact that the rise in
sk and
the rise in Tes were similar
between the two groups. There are a few plausible explanations for this
difference. It is possible that aged skin does not respond as rapidly
to direct heating because of a higher resting vascular tone or reduced
responsiveness to direct heating. Although less likely, it is also
possible that the baroreceptors in the older men buffered the increase
in SkBF to minimize the fall in MAP at the initiation of heating,
suggesting that
c in the older
men could not increase sufficiently to match the fall in peripheral
vascular resistance. The lack of a reflex inotropic response in the
older men to the initial increase in sk is
in line with this latter theory. Furthermore, there is evidence in
young men that the baroreceptors limit heat-induced active vasodilation
when combined with an orthostatic stress, such as lower body negative
pressure (12).
The lack of a difference in Tes between the groups, despite much higher SkBFs in the younger men, is more difficult to reconcile. One might suspect that the higher blood flow to the skin during direct passive heating in the young men would bring more heat from the skin to the core, resulting in a more rapid increase in core temperature. It is possible that the ~10% larger AD of the older men allowed for a greater total area of heat exchange, equalizing the rate of heat gain. It is also possible that there was a significant amount of heat directly conducted (vs. convected) through the tissues, accounting for the similar increases in Tes, although there are no data to support this latter hypothesis. It is doubtful that the younger subjects had a higher rate of evaporative heat loss, since the two groups of men were covered, with the exception of the head, forearms, and hands, with a plastic coverall that minimized evaporative heat loss. This is confirmed by the similar loss of body weight during the protocol in the two groups of men.
In summary, the purpose of this investigation was to compare the
cardiac and hemodynamic responses during direct passive heating to
limits of thermal tolerance in young and older men wearing water-perfused suits. The lower SkBF in older men during heating was
associated with a lower
c and a reduced
ability to redistribute blood from the visceral circulation. The
cardiac responses to passive heat stress were also altered as an effect
of chronological age, with the older men relying on a greater
proportion of their chronotropic reserve to compensate for a reduced
inotropic response.
| |
ACKNOWLEDGEMENTS |
|---|
The authors greatly appreciate the assistance of Jane Pierzga, Carla Thomas, Esther Brooks, and Bill Farquhar and the scientific input of Drs. E. R. Buskirk and Timothy R. McConnell. The nursing care provided by the staff of the Penn State 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, an American College of Sports Medicine Foundation Grant for Doctoral Students, and National Aeronautics and Space Administration Grant NAGW-4839. The study was also supported 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 reprint requests to W. L. Kenney.
Received 5 August 1997; accepted in final form 25 November 1997.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
1.
Allen, T. H.,
M. T. Peng,
K. P. Chen,
T. F. Huang,
C. Chang,
and
H. S. Fang.
Prediction of blood volume and adiposity in man from body weight and cube of height.
Metabolism
5:
328-345,
1956.
2.
Bratton, A. C.,
and
E. K. Marshall.
A new coupling component for sulfonylamide determination.
J. Biol. Chem.
128:
537-550,
1938.
3.
Burnum, J. F.,
J. B. Hickam,
and
H. D. McIntosh.
The effect of hypocapnia on arterial blood pressure.
Circulation
9:
89-95,
1954[Medline].
4.
Caesar, J.,
S. Shaldon,
L. Chiandussi,
L. Guevara,
and
S. Sherlock.
The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function.
Clin. Sci. (Lond.)
21:
43-57,
1961.
5.
Danziger, R. S.,
J. D. Tobin,
L. C. Becker,
E. E. Lakatta,
and
J. L. Fleg.
The age-associated decline in glomerular filtration in healthy normotensive volunteers.
J. Am. Geriatr. Soc.
38:
1127-1132,
1990[Medline].
6.
Detry, J. R.,
G. L. Brengelmann,
L. B. Rowell,
and
C. Wyss.
Skin and muscle components of forearm blood flow in directly heated resting man.
J. Appl. Physiol.
32:
506-511,
1972
7.
Dill, D. B.,
and
D. L. Costill.
Calculation of percentage changes in volume of blood, plasma, and red cell in dehydration.
J. Appl. Physiol.
37:
247-248,
1974
8.
Escourrou, P.,
B. Raffestin,
Y. Papelier,
E. Pussard,
and
L. B. Rowell.
Cardiopulmonary and carotid baroreflex control of splanchnic and forearm circulations.
Am. J. Physiol.
264 (Heart Circ. Physiol. 33):
H777-H782,
1993
9.
Grainger, S. L.,
P. W. N. Keeling,
I. M. H. Brown,
J. H. Marigold,
and
R. P. H. Thompson.
Clearance and noninvasive determination of the hepatic extraction of indocyanine green in baboons and man.
Clin. Sci. (Lond.)
64:
207-212,
1983[Medline].
10.
Ho, C. W.,
J. L. Beard,
P. A. Farrell,
C. T. Minson,
and
W. L. Kenney.
Age, fitness, and regional blood flow during exercise in the heat.
J. Appl. Physiol.
82:
1126-1135,
1997
11.
Johnson, J. M.,
G. L. Brengelmann,
and
L. B. Rowell.
Interactions between local and reflex influences on human forearm skin blood flow.
J. Appl. Physiol.
41:
826-831,
1976
12.
Kellogg, D. L.,
J. M. Johnson,
and
W. A. Kosiba.
Baroreflex control of the cutaneous active vasodilator system in humans.
Circ. Res.
66:
1420-1426,
1990[Abstract].
13.
Kenney, W. L.
Control of heat-induced vasodilation in relation to age.
Eur. J. Appl. Physiol.
57:
120-125,
1988.
14.
Kenney, W. L.
ACSM's Guidelines for Exercise Testing and Prescription (5th ed.). Baltimore, MD: Williams & Wilkins, 1995.
15.
Kenney, W. L.,
and
C.-W. Ho.
Age alters regional distribution of blood flow during moderate-intensity exercise.
J. Appl. Physiol.
79:
1112-1119,
1995
16.
Kenney, W. L.,
A. L. Morgan,
W. B. Farquhar,
E. M. Brooks,
J. M. Pierzga,
and
J. A. Derr.
Decreased active vasodilator sensitivity in aged skin.
Am. J. Physiol.
272 (Heart Circ. Physiol. 41):
H1609-H1614,
1997
17.
Kenney, W. L.,
C. G. Tankersley,
D. L. Newswanger,
D. E. Hyde,
and
S. M. Puhl.
Age and hypohydration independently influence the peripheral vascular response to heat stress.
J. Appl. Physiol.
68:
1902-1908,
1990
18.
Kenney, W. L.,
and
D. H. Zappe.
Renal vasoconstriction during exercise: effect of age (Abstract).
FASEB J.
8:
A304,
1994.
19.
Kenney, W. L.,
and
D. H. Zappe.
Effect of age on renal blood flow during exercise.
Aging Clin. Exp. Res.
6:
293-302,
1994.
20.
Kirsch, K. A.,
L. Rocker,
H. V. Ameln,
and
K. Hrynyschyn.
The cardiac filling pressure following exercise and thermal stress.
Yale J. Biol. Med.
59:
257-265,
1986[Medline].
21.
Lakatta, E. G.
Cardiovascular regulatory mechanisms in advanced age.
Physiol. Rev.
73:
413-467,
1993
22.
Martin, H. L.,
J. L. Loomis,
and
W. L. Kenney.
Maximal skin vascular conductance in subjects aged 5-85 yr.
J. Appl. Physiol.
79:
297-301,
1995
23.
Raven, P. B.
Is cardiac filling pressure the limiting factor in adjusting to heat stress?
Yale J. Biol. Med.
59:
267-279,
1986[Medline].
24.
Rowell, L. B.
Human cardiovascular adjustments to exercise and thermal stress.
Physiol. Rev.
54:
75-159,
1974
25.
Rowell, L. B.
Cardiovascular adjustments to thermal 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. 27, p. 967-1023.
26.
Rowell, L. B.,
G. L. Brengelmann,
J. R. Blackmon,
and
J. A. Murray.
Redistribution of blood flow during sustained high skin temperature in resting man.
J. Appl. Physiol.
28:
413-420,
1970.
27.
Rowell, L. B.,
G. L. Brengelmann,
and
J. A. Murray.
Cardiovascular responses to sustained high skin temperature in resting man.
J. Appl. Physiol.
27:
673-680,
1969
28.
Rowell, L. B.,
J. R. Detry,
J. R. Blackmon,
and
C. Wyss.
Importance of the splanchnic vascular bed in human blood pressure regulation.
J. Appl. Physiol.
32:
213-220,
1972
29.
Rowell, L. B.,
J. R. Detry,
G. R. Profant,
and
C. Wyss.
Splanchnic vasoconstriction in hyperthermic man
role of falling blood pressure.
J. Appl. Physiol.
31:
864-869,
1971
30.
Sackner, M. A.,
D. Greeneltch,
M. S. Heiman,
S. Epstein,
and
N. Atkins.
Diffusing capacity, membrane diffusing capacity, capillary blood volume, pulmonary tissue volume, and cardiac output measured by a rebreathing technique.
Am. Rev. Respir. Dis.
111:
157-165,
1975[Medline].
31.
Sackner, M. A.,
G. Markwell,
N. Atkins,
S. J. Birch,
and
R. J. Fernandez.
Rebreathing techniques for pulmonary capillary blood flow and tissue volume.
J. Appl. Physiol.
49:
910-915,
1980
32.
Taylor, W. F.,
J. M. Johnson,
D. S. O'Leary,
and
M. K. Park.
Modification of the cutaneous vascular response to exercise by local skin temperature.
J. Appl. Physiol.
57:
1878-1884,
1984
33.
Triebwasser, J. H.,
R. L. Johnson,
R. P. Burpo,
J. C. Campbell,
W. C. Reardon,
and
C. G. Blomqvist.
Noninvasive determination of cardiac output by a modified acetylene rebreathing procedure utilizing mass spectrometer measurements.
Aviat. Space Environ. Med.
48:
203-209,
1977[Medline].
34.
Van Acker, B. A.,
G. C. M. Koomen,
and
L. Arisz.
Drawbacks of the constant-infusion technique for measurement of renal function.
Am. J. Physiol.
268 (Renal Fluid Electrolyte Physiol. 37):
F543-F552,
1995
35.
Veith, R. C.,
J. A. Featherstone,
O. A. Linares,
and
J. B. Halter.
Age differences in plasma norepinephrine kinetics in humans.
J. Gerontol. A Biol. Sci. Med. Sci.
41:
319-324,
1986.
36.
Wesson, L. G.
Electrolyte excretion in relation to diurnal cycle of renal function.
Medicine (Baltimore)
43:
547-592,
1964.
37.
Whitney, R. J.
The measurement of volume changes in human limbs.
J. Physiol. (Lond.)
121:
1-27,
1953.
This article has been cited by other articles:
|
|
 |
|
  L. Nybo Hyperthermia and fatigue J Appl Physiol, March 1, 2008; 104(3): 871 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Kenney Human cardiovascular responses to passive heat stress J. Physiol., January 1, 2008; 586(1): 3 - 3. [Full Text] [PDF]
|
|
|
|
|
|
C. G. Crandall, T. E. Wilson, J. Marving, T. W. Vogelsang, A. Kjaer, B. Hesse, and N. H. Secher Effects of passive heating on central blood volume and ventricular dimensions in humans J. Physiol., January 1, 2008; 586(1): 293 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Wilson, C. Tollund, C. C. Yoshiga, E. A. Dawson, P. Nissen, N. H. Secher, and C. G. Crandall Effects of heat and cold stress on central vascular pressure relationships during orthostasis in humans J. Physiol., November 15, 2007; 585(1): 279 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Wilson, J. Cui, R. Zhang, and C. G. Crandall Heat stress reduces cerebral blood velocity and markedly impairs orthostatic tolerance in humans Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1443 - R1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Keller, J. Cui, S. L. Davis, D. A. Low, and C. G. Crandall Heat stress enhances arterial baroreflex control of muscle sympathetic nerve activity via increased sensitivity of burst gating, not burst area, in humans J. Physiol., June 1, 2006; 573(2): 445 - 451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Low, A. Purvis, T. Reilly, and N. T. Cable The prolactin responses to active and passive heating in man Exp Physiol, November 1, 2005; 90(6): 909 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Kenney and T. I. Musch Senescence alters blood flow responses to acute heat stress Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1480 - H1485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
) and
older men (
). Values are means ± SE. Increase in