Sustained and generalized extracellular fluid expansion following heat acclimation.

We measured intra- and extravascular body-fluid compartments in 12 resting males before (day 1; control), during (day 8) and after (day 22) a 3-week, exercise-heat acclimation protocol to investigate plasma volume (PV) changes. Our specific focus was upon the selective nature of the acclimation-induced PV expansion, and the possibility that this expansion could be sustained during prolonged acclimation. Acclimation was induced by cycling in the heat, and involved 16 treatment days (controlled hyperthermia (90 min); core temperature = 38.5 degrees C) and three experimental exposures (40 min rest, 96.9 min (s.d. 9.5 min) cycling), each preceded by a rest day. The environmental conditions were a temperature of 39.8 degrees C (s.d. 0.5 degrees C) and relative humidity of 59.2% (s.d. 0.8%). On days 8 and 22, PV was expanded and maintained relative to control values (day 1: 44.0 +/- 1.8; day 8: 48.8 +/- 1.7; day 22: 48.8 +/- 2.0 ml kg(-1); P < 0.05). The extracellular fluid compartment (ECF) was equivalently expanded from control values on days 8 (279.6 +/- 14.2 versus 318.6 +/- 14.3 ml kg(-1); n= 8; P < 0.05) and 22 (287.5 +/- 10.6 versus 308.4 +/- 14.8 ml kg(-1); n= 12; P < 0.05). Plasma electrolyte, total protein and albumin concentrations were unaltered following heat acclimation (P > 0.05), although the total plasma content of these constituents was elevated (P < 0.05). The PV and interstitial fluid (ISF) compartments exhibited similar relative expansions on days 8 (15.0 +/- 2.2%versus 14.7 +/- 4.1%; P > 0.05) and 22 (14.4 +/- 3.6% versus 6.4 +/- 2.2%; P= 0.10). It is concluded that the acclimation-induced PV expansion can be maintained following prolonged heat acclimation. In addition, this PV expansion was not selective, but represented a ubiquitous expansion of the extracellular compartment.

Human physiological responses to cold exposure.

Thermal energy is transferred within and between bodies via several avenues, but for most unprotected human cold exposures, particularly during immersion, convective heat loss dominates. Lower tissue temperatures stimulate thermoreceptors, and the resultant afferent flow elicits autonomic homoeostatic responses (thermogenesis and vasoconstriction) that regulate body temperature within a narrow range. The most powerful effector responses occur when both superficial and deep thermoreceptors are cooled simultaneously, but thermoeffector activation can also occur as a result of peripheral cooling alone. The responses to cold, and the hazards associated with cold exposure, are moderated by factors which influence heat production and heat loss, including the severity and duration of cold stimuli, accompanying exercise, the magnitude of the metabolic response, and individual characteristics such as body composition, age, and gender. Cold stress can quickly overwhelm human thermoregulation with consequences ranging from impaired performance to death. This review provides a comprehensive overview of the human physiological responses to acute cold exposure.

Interactions between temperature and human leptin physiology in vivo and in vitro.

To investigate the possibility that environmental temperature may exert physiologically significant direct, local effects on subcutaneous adipose tissue temperatures, and its secretion of leptin, we exposed healthy males ( n=12) to repeated cold-water immersion (study 1), and also incubated surgically removed human subcutaneous adipose tissue samples ( n=7) at 27 degrees, 32 degrees and 37 degrees C (study 2). In vivo immersions were conducted over 15 days (60-90 min at 18 degrees C). Regional body temperatures and plasma leptin concentrations were measured before and during immersion. Acute cold exposure suppressed plasma leptin concentration (25 min: -14%, 60 min: -22%, P=0.0001), whilst repeated cold-water immersion was associated with an increase of plasma leptin concentration relative to test day 1 (+19% day 8, +13% day 15, overall P=0.03). Leptin secretion in vitro decreased 3.7-fold as the incubation temperature decreased from 37 degrees to 27 degrees C ( P=0.001). In a compartmental model of leptin turnover in vivo, the measured (local) temperature effect on leptin secretion in vitro was more than able to account for the observed cold-induced decrease in leptin concentration in vivo. We therefore conclude that acute and repeated cold-water immersions have separate and opposing effects on circulating leptin concentrations in humans. Under our experimental conditions, the local effects of reduced subcutaneous adipose tissue temperature may be a more important contributor to the acute effects observed in vivo, than the sympathetically mediated suppression of leptin secretion.

Transition from estrogen therapy to raloxifene in postmenopausal women: effects on treatment satisfaction and the endometrium-a pilot study.

OBJECTIVE: To compare the effects of transferring from low-dose, transdermal estrogen to raloxifene with a phase of alternate-day raloxifene therapy with or without low-dose transdermal estrogen on patient satisfaction, endometrial changes, and overall safety in healthy, postmenopausal women previously administered hormone therapy. DESIGN: Healthy postmenopausal women were randomized to one of two treatment groups: raloxifene + low-dose, transdermal estrogen (RLX+E) and raloxifene + placebo (RLX+P). The study consisted of four equal phases of 8 weeks each: Phase I (low-dose, transdermal estrogen, 25 microg/day), phase II (double-blind, alternate-day raloxifene 60 mg + low-dose, transdermal estrogen or placebo patch), phase III (alternate-day RLX 60 mg + placebo patch), and phase IV (raloxifene 60 mg/day + placebo patch). Primary endpoints included patient satisfaction, endometrial changes, overall safety, and quality of life. RESULTS: Sixty women were randomized in this study. Baseline characteristics were similar between the two treatment groups. For the primary analysis (phase II to phase IV, inclusive), there were no significant differences between the therapy sequences for patient satisfaction, endometrial thickness, or quality of life. In the therapy comparison phase (phase II), mean change in patient satisfaction score was 3.2 mm (SD = 16.2) for RLX+E and -17.1 mm (SD = 38.7) for RLX+P (P = 0.003), whereas mean change in endometrial thickness was 0.8 mm (SD = 2.7) for RLX+E and -0.9 mm (SD = 1.5) for RLX+P (P = 0.021). The RLX+P group showed a significantly greater increase in vasomotor events, with a mean score change of 1.7 (SD = 1.9) compared with a mean score change of 0.2 (SD = 1.8) in the RLX+E group (P = 0.005). There were no statistically significant differences between the two therapy groups in the reporting of treatment-emergent adverse events. CONCLUSION: Gradual conversion to raloxifene from low-dose estrogen, with a progression from 60 mg every alternate day to 60 mg/day, is a viable option in potentially symptomatic, postmenopausal women.

Humid heat acclimation does not elicit a preferential sweat redistribution toward the limbs.

We tested the hypothesis that local sweat rates would not display a systematic postadaptation redistribution toward the limbs after humid heat acclimation. Eleven nonadapted males were acclimated over 3 wk (16 exposures), cycling 90 min/day, 6 days/wk (40 degrees C, 60% relative humidity), using the controlled-hyperthermia acclimation technique, in which work rate was modified to achieve and maintain a target core temperature (38.5 degrees C). Local sudomotor adaptation (forehead, chest, scapula, forearm, thigh) and onset thresholds were studied during constant work intensity heat stress tests (39.8 degrees C, 59.2% relative humidity) conducted on days 1, 8, and 22 of acclimation. The mean body temperature (Tb) at which sweating commenced (threshold) was reduced on days 8 and 22 (P < 0.05), and these displacements paralleled the resting thermoneutral Tb shift, such that the Tb change to elicit sweating remained constant from days 1 to 22. Whole body sweat rate increased significantly from 0.87 +/- 0.06 l/h on day 1 to 1.09 +/- 0.08 and 1.16 +/- 0.11 l/h on days 8 and 22, respectively. However, not all skin regions exhibited equivalent relative sweat rate elevations from day 1 to day 22. The relative increase in forearm sweat rate (117 +/- 31%) exceeded that at the forehead (47 +/- 18%; P < 0.05) and thigh (42 +/- 16%; P < 0.05), while the chest sweat rate elevation (106 +/- 29%) also exceeded the thigh (P < 0.05). Two unique postacclimation observations arose from this project. First, reduced sweat thresholds appeared to be primarily related to a lower resting Tb, and more dependent on Tb change. Second, our data did not support the hypothesis of a generalized and preferential trunk-to-limb sweat redistribution after heat acclimation.

Direct and indirect methods for determining plasma volume during thermoneutral and cold-water immersion.

Plasma volume (PV), determined indirectly from changes in haematocrit (Hct) and haemoglobin concentration ([Hb]), underestimates the absolute PV change (Evans blue dye) during thermoneutral immersion. Since PV changes during cold-water immersion have only been determined indirectly, we hypothesised that a similar underestimation may occur. Therefore, we compared the indirectly-measured PV with a direct-tracer dilution method (Evans blue dye column elution) in seven healthy males, during three, 60-min exposures: air (control; 21.2 degrees C), thermoneutral immersion (34.5 degrees C) and cold-water immersion (18.6 degrees C). During thermoneutral immersion, the directly-measured PV increased by 16.2 (1.4)% (P<0.05) and the indirectly-measured by 8.5 (0.8)% (P<0.05), with the latter underestimating the former by 43 (9.1)% (P<0.05). During cold immersion, the direct PV decreased by 17.9 (3.0)% (P<0.05) and the indirect by 8.0 (1.2)% (P<0.05), with the latter representing a 52 (6.8)% (P<0.05) underestimation of the direct PV change. Directionally-equivalent underestimations of PV change occur when using the indirect method during both thermoneutral and cold-water immersion. The assumptions inherent in the indirect method (constant F-cell ratio) appear to be violated during water immersion.

The exercise and environmental physiology of extravehicular activity.

Extravehicular activity (EVA), i.e., exercise performed under unique environmental conditions, is indispensable for supporting daily living in weightlessness and for further space exploration. From 1965-1996 an average of 20 h x yr(-1) were spent performing EVA. International Space Station (ISS) assembly will require 135 h x yr(-1) of EVA, and 138 h x yr(-1) is planned for post-construction maintenance. The extravehicular mobility unit (EMU), used to protect astronauts during EVA, has a decreased pressure of 4.3 psi that could increase astronauts' risk of decompression sickness (DCS). Exercise in and repeated exposure to this hypobaria may increase the incidence of DCS, although weightlessness may attenuate this risk. Exercise thermoregulation within the EMU is poorly understood; the liquid cooling garment (LCG), worn next to the skin and designed to handle thermal stress, is manually controlled. Astronauts may become dehydrated (by up to 2.6% of body weight) during a 5-h EVA, further exacerbating the thermoregulatory challenge. The EVA is performed mainly with upper body muscles; but astronauts usually exercise at only 26-32% of their upper body maximal oxygen uptake (VO2max). For a given ground-based work task in air (as opposed to water), the submaximal VO2 is greater while VO2max and metabolic efficiency are lower during ground-based arm exercise as compared with leg exercise, and cardiovascular responses to exercise and training are also different for arms and legs. Preflight testing and training, whether conducted in air or water, must account for these differences if ground-based data are extrapolated for flight requirements. Astronauts experience deconditioning during microgravity resulting in a 10-20% loss in arm strength, a 20-30% loss in thigh strength, and decreased lower-body aerobic exercise capacity. Data from ground-based simulations of weightlessness such as bed rest induce a 6-8% decrease in upper-body strength, a 10-16% loss in thigh extensor strength, and a 15-20% decrease in lower-body aerobic exercise capacity. Changes in EVA support systems and training based on a greater understanding of the physiological aspects of exercise in the EVA environment will help to insure the health, safety, and efficiency of working astronauts.