Executive summary and conclusions from the European Hydration Institute Expert Conference on human hydration, health, and performance.

On April 7-8, 2014, the European Hydration Institute hosted a small group of experts at Castle Combe Manor House, United Kingdom, to discuss a range of issues related to human hydration, health, and performance. The meeting included 18 recognized experts who brought a wealth of experience and knowledge to the topics under review. Eight selected topics were addressed, with the key issues being briefly presented before an in-depth discussion. Presented here is the executive summary and conclusions from this meeting.

Altered skin flowmotion in hypertensive humans.

Essential hypertensive humans exhibit attenuated cutaneous nitric oxide (NO)-dependent vasodilation. Using spectral analysis (fast Fourier transformation) we aimed to characterize the skin flowmotion contained in the laser-Doppler flowmetry recordings during local heating-induced vasodilation before and after concurrent pharmacological inhibition of nitric oxide synthase (NOS) in hypertensive and age-matched normotensive men and women. We hypothesized that hypertensive subjects would have lower total power spectral densities (PSDs), specifically in the frequency intervals associated with intrinsic endothelial and neurogenic control of the microvasculature. Furthermore, we hypothesized that NOS inhibition would attenuate the endothelial frequency interval. Laser-Doppler flowmetry recordings during local heating experiments from 18 hypertensive (MAP: 108±2mmHg) and 18 normotensive (MAP: 88±2mmHg) men and women were analyzed. Within site NO-dependent vasodilation was assessed by perfusion of a non-specific NOS inhibitor (N(G)-nitro-l-arginine methyl ester; l-NAME) through intradermal microdialysis during the heating-induced plateau in skin blood flow. Local heating-induced vasodilation increased total PSD for all frequency intervals (all p<0.001). Hypertensives had a lower total PSD (p=0.03) and absolute neurogenic frequency intervals (p<0.01) compared to the normotensives. When normalized as a percentage of total PSD, hypertensives had reduced neurogenic (p<0.001) and augmented myogenic contributions (p=0.04) to the total spectrum. NOS inhibition decreased total PSD (p<0.001) for both groups, but hypertensives exhibited lower absolute endothelial (p<0.01), neurogenic (p<0.05), and total PSD (p<0.001) frequency intervals compared to normotensives. These data suggest that essential hypertension results in altered neurogenic and NOS-dependent control of skin flowmotion and support the use of spectral analysis as a non-invasive technique to study vasoreactivity.

Influence of age on thirst and fluid intake.

Independently living older adults (over the age of 65 yr) consume adequate volumes of fluids on a daily basis. However, when challenged by fluid deprivation, a hyperosmotic stimulus, or exercise in a warm environment (all of which combine hypovolemia and hyperosmolality), older adults exhibit decreased thirst sensation and reduced fluid intake. Full fluid restoration eventually occurs, but full restoration of fluid balance is slowed. The aging process alters important physiological control systems associated with thirst and satiety. Recent evidence suggests that older men and women (i) have a higher baseline osmolality and thus a higher osmotic operating point for thirst sensation (with little or no change in sensitivity), and (ii) exhibit diminished thirst and satiety in response to the unloading (hypovolemia) and loading (hypervolemia) of baroreceptors. A diminished sensation of thirst in the elderly relative to young adults is generally absent when a volume stimulus is absent, despite higher baseline plasma osmolalities. Compared with the elderly, there are scant data associated with homeostatic control of thirst in children. Nonhomeostatic control of thirst and drinking behavior may likewise be different for children (as it is for the elderly), as compared with young adults; however, little empirical data exist on this topic. Children rarely exhibit voluntary dehydration for activities lasting 45 min or less; however, drink flavoring and sodium chloride are important promoters of drinking in active children.

Influence of hormone replacement therapy and aspirin on temperature regulation in postmenopausal women.

Postmenopausal women receiving estrogen-replacement therapy (ERT) regulate body temperature (T(b)) at a lower level than women not receiving hormone replacement therapy (untreated) and women using estrogen plus progesterone therapy (E + P), but it is not clear if reproductive hormones alter T(b) by directly acting on central thermoregulatory centers or indirectly via a secondary mediator(s). The purpose of the present investigation was to examine the possible involvement of pyrogenic cytokines and cyclooxygenase (COX) products (e.g., prostaglandins) in the regulation of T(b) in three groups of postmenopausal women (8 ERT, 7 E + P, and 8 untreated). We measured ex vivo secretion of cytokine agonists [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and -6] and modifiers (IL-2 soluble receptor, IL-1 receptor antagonist, soluble TNF receptor type I, soluble TNF receptor type II, soluble IL-6 receptor, and soluble glycoprotein 130) from peripheral blood mononuclear cells and thermoregulatory responses at rest and during 1 h of passive whole body heating in the postmenopausal women before and after 3 days of placebo or aspirin (50 mg. day(-1). kg(-1)). With and without aspirin, the ERT group had a lower baseline rectal temperature (T(re); 0.44 degrees C, P < 0.004) and a reduced T(b) threshold for cutaneous vasodilation (0.29 degrees C and 0.38 degrees C, P < 0.01) compared with the untreated and E + P groups, respectively. In the placebo condition, waking morning oral temperature (T(or)) correlated with ex vivo secretion of the proteins associated with IL-6 bioactivity. Aspirin caused significant reductions in waking T(or) in the E + P group and in baseline T(re) in the untreated group. However, the difference in thermoregulation brought about by steroid hormone treatment could not be explained by these relatively modest apparent influences by cytokines and COX products. Therefore, the altered thermoregulation induced by reproductive steroid therapy appears to occur via a mechanism distinct from a classic infection-induced fever.

Effects of hormone replacement therapy on hemodynamic responses of postmenopausal women to passive heating.

To examine the influence of chronic hormone replacement therapy (HRT) on the central and peripheral cardiovascular responses of postmenopausal women to direct passive heating, seven women taking estrogen replacement therapy, seven women taking estrogen and progesterone therapy, and seven women not taking HRT were passively heated with water-perfused suits to their individual limit of thermal tolerance. Measurements included heart rate (HR), cardiac output, blood pressure, skin blood flow, splanchnic blood flow, renal blood flow, esophageal temperature, and mean skin temperature. Cardiac output was higher in women taking estrogen and progesterone therapy than in women not taking HRT (7.12 +/- 0.70 vs. 5.02 +/- 0. 57 l/min at the limit of thermal tolerance, respectively; P < 0.05) because of a higher HR. However, when the HR data were plotted as a percentage of the maximum HR or percentage of HR reserve, there were no differences among the three groups of women. Neither splanchnic nor renal blood flow differed among the groups of women. These data suggest that HRT has little effect on the cardiovascular responses to direct passive heating.

Age and renal prostaglandin inhibition during exercise and heat stress.

Aging is associated with a number of physiological changes that may cause the kidney to rely to a greater extent on vasodilatory PGs for normal functioning. Acute exercise has been shown to cause renal vasoconstriction that may be partially buffered by vasodilatory PGs. To determine the relative importance of renal PGs during exercise in older adults, we compared the renal effects of the PG inhibitor ibuprofen (1.2 g/day for 3 days) vs. a placebo control in a cohort of eight younger (24 +/- 2 yr) and eight older (64 +/- 2 yr) women during treadmill exercise ( approximately 57% maximal oxygen consumption) in the heat (36 degrees C). This over-the-counter dose of ibuprofen reduced renal PG (i.e., PGE2) excretion by 47% (P < 0. 05). Acute exercise in the heat caused dramatic decreases in glomerular filtration rate, renal blood flow, and sodium excretion in both age groups. PG inhibition was associated with greater decreases in urine production and free water clearance (P < 0.05). There were no drug-related declines in glomerular filtration rate or renal blood flow. We conclude that PG inhibition has only modest effects on renal function during exercise. Also, the lack of hemodynamic changes with PG inhibition indicates that healthy well-hydrated older women are not in a renal PG-dependent state.

Exercise- and methylcholine-induced sweating responses in older and younger men: effect of heat acclimation and aerobic fitness.

The purpose of this investigation was to examine the effects of aging and aerobic fitness on exercise- and methylcholine-induced sweating responses during heat acclimation. Five younger [Y group-age: 23 +/- 1 (SEM) years; maximal oxygen consumption (VO2max): 47 +/- 3 ml.kg-1.min-1], four highly fit older (HO group- 63 +/- 3 years; 48 +/- 4 ml.kg-1.min-1) and five normally fit older men (NO group -67 +/- 3 years; 30 +/- 1 ml.kg-1.min-1) who were matched for height, body mass and percentage fat, were heat acclimated by daily cycle exercise (approximately 35% VO2max for 90 min) in a hot (43 degrees C, 30% RH) environment for 8 days. The heat acclimation regimen increased performance time, lowered final rectal temperature (Tre) and percentage maximal heart rate (%HRmax), improved thermal comfort and decreased sweat sodium concentration similarly in all groups. Although total body sweating rates (Msw) during acclimation were significantly greater in the Y and HO groups than in the NO group (P < 0.01) (because of the lower absolute workload in the NO group), the Msw did not change in all groups with the acclimation sessions. Neither were local sweating rates (msw) on chest, back, forearm and thigh changed in all groups by the acclimation. The HO group presented greater forearm msw (30-90 min) values and the Y group had greater back and thigh msw (early in exercise) values, compared to the other groups (P < 0.001). In a methylcholine injection test on days immediately before and after the acclimation, the order of sweat output per gland (SGO) on chest, back and thigh was Y > HO > NO, and on the forearm Y = HO > NO. No group differences were observed for activated sweat gland density at any site. The SGO at the respective sites increased in the post-acclimation test regardless of group (P < 0.01), but on the thigh the magnitude of the increase was lower in the NO (P < 0.02) and HO (P = 0.07) groups than in the Y group. These findings suggest that heat tolerance and the improvement with acclimation are little impaired not only in highly fit older but also normally fit older men, when the subjects exercised at the same relative exercise intensity. Furthermore, the changes induced by acclimation appear associated with an age-related decrease in VO2max. However methylcholine-activated SGO and the magnitude of improvement of SGO with acclimation are related not only to VO2max but also to aging, suggesting that sensitivity to cholinergic stimulation decreases with aging.

Aerobic training and cutaneous vasodilation in young and older men.

To determine the effect and underlying mechanisms of exercise training and the influence of age on the skin blood flow (SkBF) response to exercise in a hot environment, 22 young (Y; 18-30 yr) and 21 older (O; 61-78 yr) men were assigned to 16 wk of aerobic (A; YA, n = 8; OA, n = 11), resistance (R; YR, n = 7; OR, n = 3), or no training (C; YC, n = 7; OC, n = 7). Before and after treatment, subjects exercised at 60% of maximum oxygen consumption (VO2 max) on a cycle ergometer for 60 min at 36 degrees C. Cutaneous vascular conductance, defined as SkBF divided by mean arterial pressure, was monitored at control (vasoconstriction intact) and bretylium-treated (vasoconstriction blocked) sites on the forearm using laser-Doppler flowmetry. Forearm vascular conductance was calculated as forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure. Esophageal and skin temperatures were recorded. Only aerobic training (functionally defined a priori as a 5% or greater increase in VO2 max) produced a decrease in the mean body temperature threshold for increasing forearm vascular conductance (36.89 +/- 0.08 to 36.63 +/- 0.08 degrees C, P < 0.003) and cutaneous vascular conductance (36.91 +/- 0.08 to 36.65 +/- 0.08 degrees C, P < 0.004). Similar thresholds between control and bretylium-treated sites indicated that the decrease was mediated through the active vasodilator system. This shift was more pronounced in the older men who presented greater training-induced increases in VO2 max than did the young men (22 and 9%, respectively). In summary, older men improved their SkBF response to exercise-heat stress through the effect of aerobic training on the cutaneous vasodilator system.

Effects of acetaminophen and ibuprofen on renal function in the stressed kidney.

Exercise, salt restriction, and/or dehydration causes transient reductions in renal function that may be buffered by vasodilatory prostaglandins (PGs). Over-the-counter (OTC) analgesics have the potential to alter renal hemodynamics by inhibiting renal PGs. Therefore, we tested the renal effects of the maximal recommended dose of acetaminophen (Acet, 4 g/day) and ibuprofen (Ibu, 1.2 g/day) vs. a placebo (Pl) in humans subjected to progressive renal stresses. After baseline measurements, 12 fit young (25 +/- 1 yr) men and women underwent 3 days of a low (10 meq/day)-sodium diet while taking one of the drugs or Pl (crossover design). Day 4 involved dehydration (-1.6% body wt) followed by 45 min of treadmill exercise (65% maximal O2 uptake) in the heat (36 degreesC). These combined stressors caused dramatic decreases in effective renal plasma flow, glomerular filtration rate (GFR), and sodium excretion. Baseline GFR (range: 118-123 ml/min) decreased to 78 +/- 4, 73 +/- 5, and 82 +/- 5 ml/min postexercise in the Acet, Ibu, and Pl trials, respectively, with a significantly greater decrease in GFR in the Ibu trial (P < 0. 05 vs. Pl). OTC Ibu has small but statistically significant effects on GFR during exercise in a sodium- and volume-depleted state; OTC Acet was associated with no such effects.

Age, splanchnic vasoconstriction, and heat stress during tilting.

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 degrees in a thermoneutral condition and during passive heating with water-perfused suits. Measurements included heart rate (HR), cardiac output (Qc; 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 Qc 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 Qc 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.

Heat flux and storage in hot environments.

When humans are exposed to extreme ambient temperatures, or generate internal heat by exercise, the body strives to maintain internal body temperature. The core and skin temperatures attained, as well as the physiological adjustments necessary to minimize temperature excursions, are governed by (i) heat generated by working muscle, (ii) external work performed, and (iii) biophysical heat exchange with the thermal environment. This paper provides an overview of these avenues of heat production and exchange, the aspects of the thermal environment which dictate the direction and magnitude of that exchange, and the mean body temperature response from a simplified biophysical perspective.

Chronic hormone replacement therapy does not alter resting or maximal skin blood flow.

Postmenopausal women on estrogen replacement therapy (ERT) regulate body core temperature at a lower baseline level at rest in a thermoneutral environment. We conducted a series of studies to test whether, in a thermoneutral environment, chronic (>/=2 yr) oral ERT significantly alters baseline skin blood flow (SkBF) and cutaneous vascular conductance (CVC) and whether ERT alters maximal CVC (CVCmax) and SkBF in postmenopausal women. In the first set of studies, forearm blood flow (FBF) was measured by venous-occlusion plethysmography in 24 postmenopausal women: 8 not taking exogenous hormone therapy (No HRT group), 8 on ERT, and 8 receiving combination of estrogen and progesterone therapy, at rest and during prolonged (1 h) local heating of the forearm at 42 degrees C. Mean arterial pressure (MAP) was measured by brachial auscultation before each set of FBF measurements to calculate forearm vascular conductance (FVC = FBF/MAP). SkBF was measured by laser-Doppler flowmetry (LDF), and CVC was calculated as LDF/MAP and standardized as %CVCmax. Baseline FVC, %CVCmax, and maximal FVC were not significantly different among the three groups of women. In the second set of experiments, LDF in ERT and No HRT groups was measured at rest in both thermoneutral and warm environments. %CVCmax was again not significantly different between ERT and No HRT groups at thermoneutral ambient temperatures and increased similarly in the warm environment. Therefore, chronic exogenous ERT does not appear to influence either baseline or maximal SkBF.

Age alters the cardiovascular response to direct passive heating.

During direct passive heating in young men, a dramatic increase in skin blood flow is achieved by a rise in cardiac output (Qc) 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), Qc (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. Qc 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 Qc 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.

Relevance of individual characteristics for human heat stress response is dependent on exercise intensity and climate type.

Multiple heterogeneous groups of subjects (both sexes and a wide range of maximal oxygen uptake VO2max, body mass, body surface area (AD),% body fat, and AD/mass coefficient) exercised on a cycle ergometer at a relative (%VO2max, REL) or an absolute (60 W) exercise intensity in a cool (CO 21 degrees C, 50% relative humidity), warm humid (WH 35 degrees C, 80%) and a hot dry (HD 45 degrees C, 20%) environment. Rectal temperature (Tre) responses were analysed for the influence of the individual's characteristics, environment and exercise intensity. Exposures consisted of 30-min rest, followed by 60-min exercise. The Tre was negatively correlated with mass in all conditions. Body mass acted as a passive heat sink in all the conditions tested. While negatively correlated with VO2max and VO2max per kilogram body mass in most climates, Tre was positively correlated with VO2max and VO2max per kilogram body mass in the WH/REL condition. Thus, when evaporative heat loss was limited as in WH, the higher heat production of the fitter subjects in the REL trials determined Tre and not the greater efficiency for heat loss associated with high VO2max. Body fatness significantly affected Tre only in the CO condition, where, with low skin blood flows (measured as increases in forearm blood flow), the insulative effect of fat was pronounced. In the warmer environments, high skin blood flows offset the resistance offered by peripheral adipose tissue. Contrary to other studies, Tre was positively correlated with AD/mass coefficient for all conditions tested. For both exercise types used, being big (a high heat loss area and heat capacity) was apparently more beneficial from a heat strain standpoint than having a favourable AD/mass coefficient (high in small subjects). The total amount of variance in Tre responses which could be attributed to individual characteristics was dependent on the climate and the type of exercise. Though substantial for absolute exercise intensities (52%-58%) the variance explained in Tre differed markedly for relative intensities: 72% for the WH climate with its limited evaporative capacity, and only 10%-26% for the HD and CO climates. The results showed that individual characteristics play a significant role in determining the responses of body core temperature in all conditions tested, but their contribution was low for relative exercise intensities when evaporative heat loss was not restricted. This study demonstrated that effects of individual characteristics on human responses to heat stress cannot be interpreted without taking into consideration both the heat transfer properties of the environment and the metabolic heat production resulting from the exercise type and intensity chosen. Their impact varies substantially among conditions.

Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women.

This investigation examined effects of chronic (>/=2 yr) hormone replacement therapy (HRT), both estrogen replacement therapy (ERT) and estrogen plus progesterone therapy (E+P), on core temperature and skin blood flow responses of postmenopausal women. Twenty-five postmenopausal women [9 not on HRT (NO), 8 on ERT, 8 on E+P] exercised on a cycle ergometer for 1 h at an ambient temperature of 36 degrees C. Cutaneous vascular conductance (CVC) was monitored by laser-Doppler flowmetry, and forearm vascular conductance (FVC) was measured by using venous occlusion plethysmography. Iontophoresis of bretylium tosylate was performed before exercise to block local vasoconstrictor (VC) activity at one skin site on the forearm. Rectal temperature (Tre) was approximately 0.5 degrees C lower for the ERT group (P < 0.01) compared with E+P and NO groups at rest and throughout exercise. FVC: mean body temperature (Tb) and CVC: Tb curves were shifted approximately 0.5 degrees C leftward for the ERT group (P < 0.0001). Baseline CVC was significantly higher in the ERT group (P < 0.05), but there was no interaction between bretylium treatment and groups once exercise was initiated. These results suggest that 1) chronic ERT likely acts centrally to decrease Tre, 2) ERT lowers the Tre at which heat-loss effector mechanisms are initiated, primarily by actions on active cutaneous vasodilation, and 3) addition of exogenous progestins in HRT effectively blocks these effects.

Age, fitness, and regional blood flow during exercise in the heat.

During dynamic exercise in warm environments, the requisite increase in skin blood flow (SkBF) is supported by an increase in cardiac output (Qc) and decreases in splanchnic (SBF) and renal blood flows (RBF). To examine interactions between age and fitness in determining this integrated response, 24 men, i.e., 6 younger fit (YF), 6 younger sedentary (YS), 6 older fit (OF), and 6 older sedentary (OS) rested for 50 min, then exercised at 35 and 60% maximal O2 consumption (VO2max) at 36 degrees C ambient temperature. YF had a significantly higher Qc and SkBF than any other group during exercise, but fitness level had no significant effect on any measured variable in the older men. At 60% VO2max, younger subjects had significantly greater decreases in SBF and RBF than the older men, regardless of fitness level. Total flow redirected from these two vascular beds (deltaSBF + deltaRBF) followed YF >> YS > OF > OS. A rigorous 4-wk endurance training program increased exercise SkBF in OS, but deltaSBF and deltaRBF were unchanged. Under these conditions, older men distribute Qc differently to regional circulations, i.e., smaller increases in SkBF and smaller decreases in SBF and RBF. In younger subjects, the higher SkBF associated with a higher fitness level is a function of both a higher Qc and a greater redistribution of flow from splanchnic and renal circulations, but the attenuated splanchnic and renal vasoconstriction in older men does not appear to change with enhanced aerobic fitness.

Decreased active vasodilator sensitivity in aged skin.

Older men and women respond to local and reflex-mediated heat stress with an attenuated increase in cutaneous vascular conductance (CVC). This study was performed to test the hypothesis that an augmented or sustained noradrenergic vasoconstriction (VC) may play a role in this age-related difference. Fifteen young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites on the right forearm by laser-Doppler flowmetry: one site pretreated with bretylium tosylate (BT) to block the local release of norepinephrine and thus VC and an adjacent control site. Blockade of reflex VC was verified during whole body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax) induced at the end of each experiment by prolonged local heating at 42 degrees C. Neither age nor BT affected the %CVCmax (75-86%) attained at high core temperatures. During the early rise phase of CVC, the %CVCmax-change in esophageal temperature (delta T(es)) curve was shifted to the right in the older men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/- 0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04 degrees C at control and BT sites, respectively). BT had no interactive effect on this age difference, suggesting a lack of involvement of the VC system in the attenuated CVC response of individuals over the age of 60 yr. Additionally, increases in skin vascular conductance were quantitatively compared by measuring increases in total forearm vascular conductance (FVC, restricted to the forearm skin under these conditions). After the initial approximately 0.2 degrees C increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the remainder of the exercise. Decreased active vasodilator sensitivity to increasing core temperature, coupled with structural limitations to vasodilation, appears to limit the cutaneous vascular response to exertional heat stress in older subjects.

Thermoregulation at rest and during exercise in healthy older adults.

Epidemiological evidence of increased mortality among older men and women resulting from hyper- and hypothermia should not be interpreted as implying that aging per se confers an intolerance to environmental extremes. Relatively few studies have attempted to delineate the effects of chronological age from concomitant factors (such as decreases in VO2max, lowered habitual activity levels, alterations in body composition, etc.) in determining thermoregulatory responses to rest and exercise in hot environments. When the effects of chronic diseases and sedentary life-style are kept to a minimum, heat tolerance appears to be minimally compromised by age. VO2max is more important than age in predicting body temperature during exertion, even though some of the physiological mechanisms associated with heat dissipation (especially control of skin blood flow and distribution of cardiac output) are closely associated with chronological age. Dehydration effects may be magnified in older individuals, and rehydration may be compromised by age-related differences in thirst sensitivity and renal function. The efficacy of various interventions in improving thermoregulatory responses of older individuals (e.g., aerobic training and heat acclimation) has not been studied adequately. Older men and women are capable of acclimating to hot conditions, but the time course of physiological changes underlying acclimation with age may be different. Another intervention that holds promise is hormone replacement therapy in postmenopausal women, which acutely affects temperature regulation and control of body fluids in a positive direction. The chronic effects of hormone replacement therapy on thermoregulation during exercise and environmental stresses are not known. Tolerance to cold exposure under resting conditions may be less dependent on age and aerobic fitness than on body composition. Studies of older and younger subjects exercising in cold environments are lacking altogether, including important studies into the possible preventive effects of regular physical activity on physiological responses to cold stress.

Age and cardiac output during cycle exercise in thermoneutral and warm environments.

To determine whether chronological age, independent of changes in aerobic capacity, alters cardiac output (Qc), the central hemodynamic responses to intermittent incremental cycle exercise were studied in two groups of men. Qc was measured at rest and during exercise at 35%, 60%, 75%, and 85% peak aerobic capacity (VO2peak) using a CO2 rebreathing method in seven trained older (65 +/- 2 yr) and eight normally active but untrained young men (26 +/- 1 yr) matched for VO2peak and anthropometric measures. Subjects were tested in both a thermoneutral (22 degrees C) and a warm (36 degrees C) environment to investigate possible differential cardiovascular responses to exercise in the heat. Only subjects with no history of pulmonary, cardiac, neuromuscular, or endocrine disease and a normal electrocardiogram were studied. The older men had significantly lower (P < 0.05) Qc relative to the younger men at intensities greater than 60% VO2peak in both environmental conditions. At these higher intensities, the older men had a significantly higher stroke volume (SV) and lower heart rate (HR) (P < 0.05). A higher arteriovenous oxygen difference ((a-v)O2)) compared with their younger counterparts enabled the older men to exercise at the same absolute intensity, most likely because of training induced changes in left-ventricular performance and oxygen extraction. The addition of an exogenous heat source did not alter the Qc response in either group of men; however, a higher HR (P < 0.05) and smaller SV (P > 0.05) were observed in the young men during exercise in the heat. This may reflect previously reported differences in the skin blood flow response of VO2peak-matched young and older men during exercise. It is suggested that endurance trained older men can enhance left-ventricular performance to augment SV, but not sufficiently to maintain Qc in light of an attenuated HR response during exercise at intensities above 60% VO2peak.

Reflex peripheral vasoconstriction is diminished in older men.

The purpose of this study was to compare reflex control of limb blood flow in healthy young (Y; 26 +/- 2 yr) and older (O;61 +/- 2 yr) men during whole body cooling under resting conditions. To better isolate the effect of chronological age, the two age groups (n = 6 per group) were closely matched for maximal oxygen uptake, body surface area, skinfold thickness, and fat-free weight. Subjects sat in an environmentally controlled chamber clad in standardized (0.6-clo) light cotton clothing at a dry-bulb temperature (Tdb) of 28 degrees C. After 30 min, Tdb was decreased by 2 degrees C every 5 min until Tdb = 10 degrees C, where it was held constant for the remainder of the 120-min session. Esophageal and mean skin temperatures were monitored continuously. Forearm blood flow (FBF) was measured every 5 min by venous occlusion plethysmography by using a mercury-in-Silastic strain gauge while arm temperature between the wrist and elbow was clamped at 37.2 +/- 0.1 degrees C by localized warm air heating. In this way, limb vasoconstriction was driven solely by thermoregulatory reflexes and not by direct effects of localized cooling. Mean skin temperature decreased at a similar rate and to a similar extent (by approximately 6 degrees C over a 2-h period) in both age groups, whereas esophageal temperature was relatively unaffected. In response to the local heating, the Y group maintained a significantly higher FBF than did the O group during the initial 30 min but decreased FBF during the cooling phase at a greater rate and to a greater extent than did the O group, leading to a significantly lower FBF during the final 30 min (at Tdb = 10 degrees C). Because there was no age difference in the mean arterial pressure response, similar effects of age were seen on forearm vascular conductance (FBF/mean arterial pressure). It was concluded that older men have a diminished reflex limb vasoconstrictor response to skin cooling. Furthermore, this difference in control of peripheral blood flow appears to be related to age per se; i.e., it is not a reflection of age-related differences in maximal oxygen uptake or body composition.