Comparison of thermoregulatory responses between men and women immersed in cold water.

Eleven women (age = 24.4 +/- 6.3 yr, mass = 65.0 +/- 7.8 kg, height = 167 +/- 8 cm, body fatness = 22.4 +/- 5.9%, mean +/- SD) were immersed to neck level in 18 degrees C water for up to 90 min for comparison of their thermal responses with those of men (n = 14) in a previous similarly conducted protocol. Metabolic rate increased about three times resting levels in men and women, whereas the rate of rectal temperature cooling (DeltaT(re)/Deltat) in women (0.47 degrees C/h) was about one-half that in men. With use of all data, DeltaT(re)/Deltat correlates with the ratio of body surface area to size and the metabolic rate of shivering correlates inversely to the square root of body fatness. No significant gender differences in total metabolic heat production normalized for body mass or surface area were found among subjects who completed 90 min of immersion (9 women and 7 men). Nor was there a gender difference in the overall percent contribution ( approximately 60%) of fat oxidation to total heat production. Blood concentrations of free fatty acids, glycerol, beta-hydroxybutyrate, and lactate increased significantly during the 90-min immersion, whereas muscle glycogen sampled from the right quadriceps femoris vastus lateralis decreased (free fatty acids, glycerol, and beta-hydroxybutyrate were higher in women). When the subjects were subgrouped according to similar body fatness and 60 min of immersion (6 women and 5 men), no significant gender differences emerged in DeltaT(re)/Deltat, energy metabolism, and percent fat oxidation. These findings suggest that no gender adjustments are necessary for prediction models of cold response if body fatness and the ratio of body surface area to size are taken into account and that a potential gender advantage with regard to carbohydrate sparing during cold water immersion is not supported.

Cold stress increases lipolysis, FFA Ra and TG/FFA cycling in humans.

BACKGROUND: To characterize the important changes in the selection and mobilization of metabolic fuel during cold stress, six males rested for 3 h at 29 degrees C and at 5 degrees C dressed only in shorts while 2H5 glycerol, 1-13C palmitate and 6,6 2H2 glucose were continuously infused for 3 h in each condition to determine their rate of turnover (Ra). METHODS: Metabolic rate (M) as well as rates of carbohydrate (CHOox) and lipid oxidation (FATox) were assessed by indirect calorimetry whereas all isotopic enrichments were determined by mass spectrometry. RESULTS: Cold exposure decreased rectal and mean skin temperatures and increased M, FATox and CHOox compared with the same test at thermal neutrality (p<0.05). As expected, cold increased plasma glucose Ra and plasma FFA Ra (from 4.58+/-0.19 to 14.69+/-1.07 micromol kg(-1) x min(-1); p < 0.05). However, in absolute terms, plasma FFA Ra in the cold remained more than twice greater than FATox (FATox only increased up to 6.9 +/-0.85 micromol kg(-1) x min(-1)), suggesting an enhanced non-oxidative disposal of fatty acids (i.e., TG/FFA cycling) to account for all FFA Ra. Indeed, cold increased extracellular TG/FFA recycling rate (2.23+/-0.40 vs 7.77+/-1.19 micromol kg(-1) x min(-1); p<0.05) whereas intracellular cycling was unaffected. CONCLUSION: Even though lipolysis and FFA Ra are greatly increased by cold stress in humans, the present results demonstrate that only about half the rate of FFA Ra is ultimately oxidized, suggesting that under the present cold conditions: 1) non-oxidative FFA disposal or TG/FFA cycling is significantly enhanced; 2) white adipose tissue-derived fatty acids could easily account for most of FATox. The results further emphasize the importance of the TG/FFA cycle in amplifying the ability of stored TG to react quickly to major changes in energy expenditure induced by a sustained cold stress.

Plasma glucose turnover during cold stress in humans.

To clarify the source of increased carbohydrate oxidation during cold stress, six males rested for 3 h at 29 and 10 degrees C dressed only in shorts. After priming the blood glucose and bicarbonate pools, [U-13C6]glucose was infused for 3 h in each condition to determine the plasma glucose rate of appearance (Ra) or turnover under relative steady-state conditions. Plasma enrichment (mol %excess) was determined by selective ion-monitoring gas chromatography-mass spectrometry. Cold exposure decreased rectal temperature and mean skin temperature and increased heat debt, metabolic rate, and whole body lipid and carbohydrate oxidation (CHOox) compared with the same subjects at thermal neutrality (P < 0.05). Cold exposure significantly increased Ra from 13.18 +/- 0.70 to 16.22 +/- 0.43 mumol.kg-1.min-1 (P < 0.05). Plasma glucose clearance was elevated commensurately by the cold (from 2.68 +/- 0.16 to 3.55 +/- 0.14 ml.kg-1.min-1; P < 0.05). If we assume that Ra is completely oxidized (thus equivalent to maximum rates of plasma glucose oxidation) [J. A. Romijn, E. F. Coyle, L. S. Sidossis, A. Gastaldelli, J. F. Horowitz, E. Endert, and R. R. Wolfe. Am. J. Physiol. 265 (Endocrinol. Metab. 28): E380-E391, 1993], the minimum rates of glycogen and lactate oxidation in the cold would be the difference between CHOox and glucose oxidation (approximately 14.0 +/- 3.0 mumol.kg-1.min-1). Therefore, under the present laboratory conditions, 54% of CHOox would be fueled by plasma glucose oxidation, whereas the remaining 46% would be derived from the combination of glycogen and lactate oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of modafinil on heat production and regulation of body temperatures in cold-exposed humans.

Military personnel often undergo sustained operations that affect vigilance and alertness. Pharmacological agents may be used to enhance vigilance. Most such agents also have thermogenic properties. Whether a new promising stimulant, modafinil (Lyons and French, Aviat. Space Environ. Med. 1991; 62:432-435), has a beneficial effect on cold tolerance in the military context, is not known. The goal of this study was, therefore, to evaluate the effect of this new drug on thermal balance and the regulation of body temperatures in neutral conditions and when challenged by a cold exposure. Nine subjects underwent three trials each: two in the cold (3 h at rest, 10 degrees C) 0.5 h after the ingestion of either placebo or modafinil (200 mg), and one in thermal neutrality with modafinil (same conditions except Tdb = 29.3 degrees C). As expected, cold produced a drop in Tre and Tsk and an increase in Vo2. Although non-significant, there was a tendency for a slightly greater drop in Tre with modafinil (0.65 degrees C vs. 0.57 degrees C with placebo). A similar tendency was found for the heat debt (S) which was greater with modafinil than with placebo (16.1 +/- 0.7 vs. 14.7 +/- 0.6 kJ.kg-1, respectively, +9.5%, p = 0.11). This tendency appears to be the combined result of a slightly lower mean heat production during the test and a slightly greater mean dry heat loss. When tested at thermal neutrality, the drug had no effect on any thermal or metabolic parameters. The results demonstrate that the ingestion of a single dose of modafinil has no significant acute effect on thermal balance in neutral conditions and on thermoregulation in normal subjects exposed to cold. However, a tendency for slightly greater cooling was noted with modafinil. It is not known whether the use of modafinil in conjunction with sleep deprivation (a likely scenario) could magnify this effect.

Effects of ephedrine/xanthines on thermogenesis and cold tolerance.

This paper reviews the use of ephedrine (E) and xanthines (X) to improve thermogenesis and cold tolerance. Recent experiments in cold-exposed subjects have shown that the beneficial effects of ingesting an E/caffeine (C) capsule on metabolic rate (M), heat debt, deep body core temperature (Tre) (P < 0.05) is entirely comparable to that observed with an E/C/theophylline (T) capsule. Although T has been reported to reduce the drop in Tre in several studies, these improvements are difficult to explain in the absence of changes in M. A theobromine-based commercial sports bar (Cold Buster) has been similarly shown to reduce the drop in Tre. However, such a claim could not be confirmed in our lab, even in two studies performed under different environmental conditions. Despite an increase in M in some studies, C had no effect on Tre in the cold. It is concluded that E/X represent, at the moment, the best pharmacological agents to enhance cold thermogenesis and to delay the onset of hypothermia in humans.

Is energy substrate mobilization a limiting factor for cold thermogenesis?

Energy substrate mobilization has been suggested as being a limiting factor for the rate of cold-induced thermogenesis (M), and consequently in delaying hypothermia. The evidence supporting this hypothesis in humans, however, is not convincing and the hypothesis has yet to be tested in a rigorous manner using a full heat balance analysis (partitional calorimetry). The goal of this study was therefore to re-investigate whether enhancing energy substrate mobilization by feeding cold-exposed subjects would improve M and affect heat debt (S; the minute-by-minute balance of M and heat losses) as well as rectal (Tre) and mean skin temperatures (Tsk). Nine healthy semi-nude fasted subjects were exposed to 5 degrees C (3 h at rest, 1 m.s-1 wind) on three occasions following the ingestion at min 0 and 90 of either: (1) a placebo, (2) 710 kJ of pure carbohydrates (100%-CHO), or (3) 710 kJ of a high-carbohydrate bar (High-CHO). As expected in the cold, Tre and Tsk decreased whereas M, S and heat losses increased (P < 0.01). However, there were no differences between treatments, including the final Tre [mean (SEM); 36.4 (0.2); 36.5 (0.3) and 36.5 (0.2) degrees C for the placebo, 100%-CHO and High-CHO tests, respectively]. During the 100%-CHO treatment, rates of carbohydrate oxidation were the highest and fat oxidation the lowest (P < 0.05), whereas the High-CHO treatment caused smaller changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy metabolism during cold exposure.

Recent advances on the influence of cold exposure on energy metabolism in animals and humans are summarized. Although the cold-induced enhancements in carbohydrate metabolism have been the focus of numerous studies, it was only recently that pieces of evidence from animal studies have suggested that cold exposure exerts an insulin-like effect on peripheral tissue glucose uptake, which appears to proceed primarily via insulin-independent pathways. Interestingly, this phenomenon was observed in insulin-sensitive tissues of warm- a well as cold-adapted rats. Whereas previous human studies have concentrated on the cold-induced changes in basal levels of hormones and metabolic substrates, recent work from our laboratory has demonstrated that exposure to cold at rest shifts substrate utilization from mainly lipids at thermal neutrality to carbohydrates, representing the main fuel for shivering thermogenesis. Further investigation has revealed that the marked increment in carbohydrate oxidation in cold-exposed humans is derived from a greater utilization of both circulating glucose and intramuscular glycogen. With respect to lipid metabolism, recent studies have shown that the cold-induced increase in lipid oxidation in man is fuelled primarily by the fatty acids released from white adipose tissue triglycerides (TG) and possibly intramuscular TG, not plasma TG. One practical application of this work on energy metabolism in the cold resides in the pharmacological approach to improve cold tolerance, where pharmacological agents that alter energy metabolism and substrate utilization could be used to enhance cold thermogenesis and produce warmer body temperatures.

Determination of heat debt in the cold: partitional calorimetry vs. conventional methods.

Measurements of core temperature (Tc) at different sites produce on some occasions different cooling curves in cold-exposed humans, suggesting that the corresponding thermometric heat debts (HD) could be equally different when calculated by conventional methods [via the change in either Tc or mean body temperature (Tb)]. The present study also compared these thermometric HD values with the calorimetric HD obtained by partitional calorimetry (S). Nine subjects who showed similar initial but different final Tc [rectal (Tre) and auditory canal temperatures (Tac)] during nude cold exposure (2 h at 1 degrees C at rest) were used. Tc-derived HD corresponded to a heat gain of 12 +/- 21 kJ and an HD of 78 +/- 20 kJ with use of Tre and Tac, respectively, whereas the Tb-derived HD varied from 266 +/- 35 to less than or equal to 1,479 +/- 71 kJ with the use of various well-known Tb weighing coefficients. In contrast, S corresponded to 504 +/- 79 kJ, a level that could have been obtained only if the thermoneutral/cold Tb weighing coefficients had been 0.818/0.818 for Tre and 0.865/0.865 for Tac. The results demonstrate that calculation by conventional methods can markedly overestimate or underestimate HD. These differences could not be explained by the site chosen to represent Tc, inasmuch as about the same effect was observed with use of either Tre or Tac. It is concluded that the thermometric value of HD in the cold is not, at least under the present conditions, as accurate and reliable as S.

Limb blood flow while wearing aircrew chemical defense ensembles in the heat with and without auxiliary cooling.

The effect of auxiliary air cooling on endurance time and limb blood flow in the heat (37 degrees C, 50% r.h., target time = 150 min) while wearing aircrew chemical defense (CD) ensembles was examined. Eight males were dressed in aircrew CD ensembles with or without an air-cooled vest. After an initial 10 min treadmill walk and 20 min of seated rest, the subjects alternately rested and exercised on a cycle ergometer (10 min rest, 10 min exercise) resulting in an overall metabolic rate of 240 W. Arm and leg blood flow (ABF, LBF), determined by venous occlusion plethysmography, were significantly lower with air cooling (AC) than with no cooling (NC) during the same time period (p less than 0.05). Endurance time was much greater with AC than with NC (150 min AC vs. 92 +/- 0.08 min NC, p less than 0.01). Arm and calf skin temperatures, rectal temperature and heart rate were all significantly lower with AC than with NC (p less than 0.05) after the onset of the cycle exercise. The results show that the use of the air-cooled vest under these conditions was able to increase heat tolerance and reduce blood flow to the periphery.

How should body heat storage be determined in humans: by thermometry or calorimetry?

The aim of this study was to determine whether in humans there are differences in the heat storage calculated by partitional calorimetry (S, the balance of heat gains and heat losses) compared to the heat storage obtained by conventional methods (thermometry) via either core temperature or mean body temperatures (Tb = 0.8Tc + 0.2Tsk, where Tc is core temperature and Tsk is mean skin temperature) when two different sites are used as an index of Tc [rectal (T(re)) and auditory canal (T(ac)) temperatures]. Since women respond to the heat differently than men, both sexes were studied. After a stabilisation period at thermal neutrality, six men and seven women were exposed to a globe temperature of 50 degrees C, relative humidity of 17% and wind speed of 0.8-1.0 m.s-1 for 90 min semi-nude at rest, where T(re), T(ac), Tsk, metabolic rate, dry (radiant + convective heat exchange) and evaporative heat losses, S, heat storage by Tc (STc) and heat storage by Tb (STb) were assessed every minute. In the mean, S was equal to 350.8(SEM 49.6) kJ whereas STc amounted to only 114.6(SEM 16.2) and 196.7(SEM 32.3) kJ for T(re) and T(ac), respectively (P less than 0.05). Final STb(re) underestimated S by 49% [177.7(SEM 23.0) kJ; P less than 0.05] whereas STb(ac) was not significantly different than S [255.7(SEM 37.9) kJ]. In the women, S corresponded to a total of 294.3(SEM 23.2) kJ, a value that was very similar to the STb(ac) [262.6(SEM 31.0) kJ], whereas STb(re) under-predicated S by 35% [190.4(SEM 26.3) kJ; P less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow and muscle bio-energetics by 31P-nuclear magnetic resonance after local cold acclimation.

To clarify the origin of local cold adaptation and to define precisely its influence on muscle bio-energetics during local exercise, five subjects were subjected to repeated 5 degrees C cold water immersion of the right hand and forearm. The first aim of our investigation was therefore carried out by measuring local skin temperatures and peripheral blood flow during a cold hand test (5 degrees C, 5 min) followed by a 10-min recovery period. The 31P by nuclear magnetic resonance (31PNMR) muscle bio-energetic changes, indicating possible heat production changes, were measured during the recovery period. The second aim of our investigation was carried out by measuring 31PNMR muscle bioenergetics during handgrip exercise (10% of the maximal voluntary contraction for 5 min followed by a 10-min recovery period) performed both at a comfortable ambient temperature (22 degrees C; E) and after a cold hand test (EC), before and after local cold adaptation. Local cold adaptation, confirmed by warmer skin temperatures of the extremities (+30%, P less than 0.05), was related more to an increased peripheral blood flow, as shown by the smaller decrease in systolic peak [-245 (SEM 30) Hz vs -382 (SEM 95) Hz, P less than 0.05] than to a change in local heat production, because muscle bioenergetics did not vary. Acute local cold immersion decreased the inorganic phosphate:phosphocreatine (PC) ratio during EC compared to E [+0.006 (SEM 0.010) vs +0.078 (SEM 0.002) before acclimation and +0.029 (SEM 0.002) vs +0.090 (SEM 0.002) after acclimation respectively, P less than 0.05] without significant change in the PC:beta-adenosine triphosphate ratio and pH. Local adaptation did not modify these results statistically. The recovery of PC during E increased after acclimation [9.0 (SEM 0.2) min vs 3.0 (SEM 0.4) min, P less than 0.05]. These results suggested that local cold adaptation is related more to peripheral blood flow changes than to increased metabolic heat production in the muscle.

General and local cold adaptation after a ski journey in a severe arctic environment.

It is hypothesized that some of the variability in the conclusions of several human cold adaptation studies could be explained if not only were the changes in core and shell temperatures taken into account, before and after cold adaptation, but also the absolute temperatures and metabolic rate in both thermally neutral environments and in the cold. Such an approach was used in a group of volunteers before and after a ski journey (3 weeks at -20 to -30 degrees C) across Greenland. Eight subjects were submitted to cold tests (Tdb = 1 degree C, r.h. = 40%, wind speed = 0.8 m.s-1) for 2 hours. Thermoregulatory changes were also monitored in a neutral environment (Tdb = 30 degrees C). In the neutral environment, the arctic journey increased metabolic rate (11.2%; P less than 0.05) and mean skin temperature [Tsk: 33.5 (SEM 0.2) degrees C vs 32.9 (SEM 0.2) degrees C, P less than 0.05]. During the cold test, the arctic journey was associated with a lower final rectal temperature [36.8 (SEM 0.2) degrees C vs 37.3 (SEM 0.2) degrees C, P less than 0.01], a lower final Tsk [20.7 (SEM 0.4) degrees C vs 21.2 (SEM 0.3) degrees C, P less than 0.01] with no change in metabolic heat production. These observations are indicative of an hypothermic insulative isometabolic general cold adaptation, which was associated with a local cold adaptation of the extremities, as shown by warmer foot temperatures [12.3 (SEM 0.9) degrees C vs 9.8 (SEM 0.9) degrees C, P less than 0.001].

Heat balance of subjects wearing protective clothing with a liquid- or air-cooled vest.

The goals of this study were, first, to determine the extent of the heat strain induced by wearing the Canadian Forces (CF) aircrew chemical defence individual protection ensemble (CD IPE) under simulated hot cockpit conditions, and second, to determine the effectiveness of a liquid cooled (LC) and an air-cooled (AC) vest in relieving such heat strain. Seven (7) healthy male subjects were subjected to three heat exposures (37 degrees C, 50% r.h., for 150 min, time-weighted metabolic rate of about 240 W, 1 week apart) either with no cooling (NC), LC or AC vests. NC was only tolerated for 95 +/- 5 min, whereas all subjects completed the 150-min tests with AC or LC (p less than 0.01). The large rate of increase in rectal temperature (Tre) during NC (1.00 +/- 0.05 degrees C/h) was attenuated by 51% with LC and by an even greater amount with AC (64%, p less than 0.01). NC entailed a sweat rate of almost 1 kg/h, which was reduced 38% by LC and 51% by AC (p less than 0.01). The combined dry and evaporative heat losses (HEKC of LC and AC vests were significantly greater than that of NC (164 +/- 7 and 181 +/- 9 vs. 124 +/- 9 W, respectively; p less than 0.01). The results demonstrate that subjects wearing CF aircrew IPE under simulated hot cockpit conditions can only tolerate 95 min of the 150-min test, and experience significant heat strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulatory effects of cold exposure and cold acclimation on glucose uptake in rat peripheral tissues.

The effects of cold exposure on the net rates of 2-[3H]deoxy-D-glucose uptake (Ki) in rat peripheral tissues were investigated comparatively in warm- and cold-acclimated animals to determine whether cold acclimation induces regulatory alterations in glucose metabolism. Acute exposure of warm-acclimated (25 degrees C) rats to cold (48 h at 5 degrees C) markedly increased the Ki values in red and white skeletal muscles (2-5 times), in the heart (8 times), in several white adipose tissue (WAT) depots (4-20 times), and in brown adipose tissue (BAT) (110 times). After cold acclimation (3 wk at 5 degrees C), the Ki values further increased in the heart (15 times) and WAT (up to 29 times) but decreased in BAT (36 times). Remarkably, glucose uptake was still increased in muscles of cold-exposed/cold-acclimated animals (that do not shiver), demonstrating that enhanced glucose uptake may occur in muscles in the absence of shivering thermogenesis (or contractile activity). When cold-acclimated rats were returned to the warm for 18 h, the Ki values of all tissues, except WAT, returned to control levels. Cold exposure synergistically potentiated the stimulation of tissue glucose uptake induced by a maximal effective dose of insulin (0.5 U/kg iv) in warm- as well as in cold-acclimated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of cold exposure on plasma triglyceride clearance in humans.

Recent human studies have shown that cold exposure increases lipid oxidation, even when the oxidation of circulating free fatty acid (FFA) is markedly reduced by the ingestion of nicotinic acid, thus seriously questioning the importance of FFA for lipid oxidation in the cold-exposed humans. It was therefore hypothesized that similarly to prolonged exercise, fatty acids from plasma triglycerides (TG) are important energy substrates for oxidation during prolonged cold exposure in man. The goal of this study was to determine the influence of cold exposure on an index of plasma TG utilization, the intravenous fat tolerance test (IVFTT). To evaluate the possibility of a delayed increase in fat tolerance, a second cold exposure and an IVFTT were also performed 24 hours after the first cold exposure. Seven healthy males (fasting, seminude) were subjected to an IVFTT (1 mL/kg 10% Intralipid) on three occasions while resting for 160 minutes: (1) at 29 degrees C, (2) in the cold (10 degrees C, 1 m/s wind), and (3) at 10 degrees C 24 hours after the first cold test. One week separated the warm test from the cold tests. Cold exposure reduced mean body temperature by 3.4 +/- 0.1 degree C and increased energy expenditure 2.5 times in comparison to warm values (P less than .01). It also increased fat oxidation by 70% (P less than .05) and plasma glycerol levels (P less than .05), but did not alter fat tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of caffeine on metabolic responses of men at rest in 28 and 5 degrees C.

Cold stress and caffeine ingestion are each reported to increase plasma catecholamines, free fatty acid (FFA) concentrations, and energy metabolism. This study examined the possible interaction of these two metabolic challenges in four double-blind counterbalanced trials. Young adult men (n = 6) ingested caffeine (5 mg/kg) or placebo (dextrose, 5 mg/kg) and rested for 2 h in 28 or 5 degrees C air. Cold stress alone elevated (P less than 0.05) plasma norepinephrine, metabolism (O2 consumption, VO2), and respiratory exchange ratio (RER). Caffeine alone increased (P less than 0.05) plasma epinephrine and FFA but not RER. When the two challenges were combined (caffeine plus 5 degrees C for 2 h) norepinephrine and epinephrine were increased (P less than 0.05) as was FFA. However, VO2, RER, and skin and rectal temperatures were not different from the responses observed at 5 degrees C after placebo ingestion. The data suggest that caffeine selectively increases plasma epinephrine, whereas cold air increases norepinephrine. During the cold exposure, increasing epinephrine and FFA above normal levels did not appear to influence the metabolic or thermal responses to the cold stress. In fact the increase in RER suggested a greater carbohydrate oxidation.

Computer acquisition and analysis of skin temperature and heat flow data from heat flux transducers.

A computer-controlled system for the collection and analysis of skin temperature and heat flow data originating from an array of heat flux transducers is described. The system is based on a program ('THERMAL') that reads, stores, prints and displays skin temperatures and heat flow data every 2 min for up to 4 h. It also simultaneously calculates important environmental physiology parameters such as mean skin and mean body temperatures as well as mean heat flow according to four different combinations of transducers such as the established 3-, 4-, 7- and 12-point (site) formulae. Core temperature, heart rate and environmental condition indices such as dry bulb, wet bulb and globe temperatures are also continuously monitored.

Mechanism of enhanced cold tolerance by an ephedrine-caffeine mixture in humans.

The influence of a thermogenic mixture of ephedrine- (1 mg/kg) caffeine (2.5 mg/kg) on cold tolerance was investigated in nine healthy young male subjects during two seminude exposures to cold air (3 h at 10 degrees C). The drug ingestion reduced the total drop in core, mean skin, and mean body temperatures (P less than 0.01), thus producing significantly warmer final core, mean skin, and mean body temperatures compared with the placebo ingestion. The drug ingestion increased the total 3-h energy expenditure by 18.6% compared with that of the placebo ingestion in the cold (P less than 0.01). By means of the nonprotein respiratory exchange ratio to calculate the rates of substrate oxidation, it was found that the drug ingestion increased carbohydrate oxidation by as much as 41.7% above that of the placebo (P less than 0.05). In contrast, the drug mixture had no significant influence on lipid or protein metabolism. The results demonstrate that the ingestion of an ephedrine-caffeine mixture improves cold tolerance in humans by significantly increasing body temperatures in the cold. These improvements were not caused by an increased conservation of heat but by a greater energy expenditure, which appears to be dependent on an enhanced carbohydrate utilization.

Thrombophlebitis following intravenous glucose in the cold.

In an effort to characterize the role of carbohydrate metabolism during the hypermetabolic state associated with whole body cooling, oral (n = 6) and intravenous (iv; n = 3) glucose tolerance tests (GTT) were performed in nude subjects. Unexpectedly, 1-2 wks after the completion of their iv GTT (50% dextrose) in the cold, superficial thrombophlebitis was diagnosed in all 3 subjects. No subject developed thrombophlebitis after the oral GTT in the warm and cold, nor after the iv GTT in the warm. Since this complication was not observed in further testing with isotonic iv solutions under identical conditions in the cold as above, we conclude that the adverse reaction is the result of an interaction between whole body cooling or vasoconstriction and the hypertonicity of the dextrose solution. Environmental physiologists and medical officers should be aware of this complication.