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In this study, we extended our previously developed anatomically detailed three-dimensional (3-D) thermoregulatory virtual human model for predicting heat stress to allow for predictions of heat and cold stress in one unified model. Starting with the modified Pennes bioheat transfer equation to estimate the spatiotemporal temperature distribution within the body as the underlying modeling structure, we developed a new formulation to characterize the spatial variation of blood temperature between body elements and within the limbs. We also implemented the means to represent heat generated from shivering and skin blood flow that apply to air exposure and water immersion. Then, we performed simulations and validated the model predictions with experimental data from nine studies, representing a wide range of heat- and cold-stress conditions in air and water and physical activities. We observed excellent agreement between model predictions and measured data, with average root mean squared errors of 0.2°C for core temperature, 0.9°C for mean skin temperature, and 27 W for heat from shivering. We found that a spatially varying blood temperature profile within the limbs was crucial to accurately predict core body temperature changes during very cold exposures. Our 3-D thermoregulatory virtual human model consistently predicted the body's thermal state accurately for each of the simulated hot and cold environmental conditions and exertional heat stress. As such, it serves as a reliable tool to assess whole body, localized tissue, and, potentially, organ-specific injury risks, helping develop injury prevention and mitigation strategies in a systematic and expeditious manner.

The pathogenesis of metabolic diseases such as obesity and type 2 diabetes are characterized by a progressive dysregulation in energy partitioning, often leading to end-organ complications. One emerging approach proposed to target this metabolic dysregulation is the application of mild cold exposure. In healthy individuals, cold exposure can increase energy expenditure and whole body glucose and fatty acid utilization. Repeated exposures can lower fasting glucose and insulin levels and improve dietary fatty acid handling, even in healthy individuals. Despite its apparent therapeutic potential, little is known regarding the effects of cold exposure in populations for which this stimulation could benefit the most. The few studies available have shown that both acute and repeated exposures to the cold can improve insulin sensitivity and reduce fasting glycemia in individuals with type 2 diabetes. However, critical gaps remain in understanding the prolonged effects of repeated cold exposures on glucose regulation and whole body insulin sensitivity in individuals with metabolic syndrome. Much of the metabolic benefits appear to be attributable to the recruitment of shivering skeletal muscles. However, further work is required to determine whether the broader recruitment of skeletal muscles observed during cold exposure can confer metabolic benefits that surpass what has been historically observed from endurance exercise. In addition, although cold exposure offers unique cardiovascular responses for a physiological stimulus that increases energy expenditure, further work is required to determine how acute and repeated cold exposure can impact cardiovascular responses and myocardial function across a broader scope of individuals.

Combining cooling or heating applications with exercise training to enhance performance and muscle adaptations. J Appl Physiol 129: 353–365, 2020. First published July 9, 2020; doi:10.1152/japplphysiol.00322.2020.—Athletes use cold water immersion, cryotherapy chambers, or icing in the belief that these strategies improve postexercise recovery and promote greater adaptations to training. A number of studies have systematically investigated how regular cold water immersion influences long-term performance and muscle adaptations. The effects of regular cold water immersion after endurance or high-intensity interval training on aerobic capacity, lactate threshold, power output, and time trial performance are equivocal. Evidence for changes in angiogenesis and mitochondrial biogenesis in muscle in response to regular cold water immersion is also mixed. More consistent evidence is available that regular cold water immersion after strength training attenuates gains in muscle mass and strength. These effects are attributable to reduced activation of satellite cells, ribosomal biogenesis, anabolic signaling, and muscle protein synthesis. Athletes use passive heating to warm up before competition or improve postexercise recovery. Emerging evidence indicates that regular exposure to ambient heat, wearing garments perfused with hot water, or microwave diathermy can mimic the effects of endurance training by stimulating angiogenesis and mitochondrial biogenesis in muscle. Some passive heating applications may also mitigate muscle atrophy through their effects on mitochondrial biogenesis and muscle fiber hypertrophy. More research is needed to consolidate these findings, however. Future research in this field should focus on 1) the optimal modality, temperature, duration, and frequency of cooling and heating to enhance long-term performance and muscle adaptations and 2) whether molecular and morphological changes in muscle in response to cooling and heating applications translate to improvements in exercise performance.

Cold environmental temperatures during exercise and recovery alter the acute response to cellular signaling and training adaptations. Approximately 3 wk is required for cold temperature acclimation to occur. To determine the impact of cold environmental temperature on training adaptations, fitness measurements, and aerobic performance, two groups of 12 untrained male subjects completed 1 h of cycling in 16 temperature acclimation sessions in either a 7°C or 20°C environmental temperature. Fitness assessments before and after acclimation occurred at standard room temperature. Muscle biopsies were taken from the vastus lateralis muscle before and after training to assess molecular markers related to mitochondrial development. Peroxisome proliferator-activated receptor-γ coactivator 1α ( PGC-1α) mRNA was higher in 7°C than in 20°C in response to acute exercise before training ( P = 0.012) but not after training ( P = 0.813). PGC-1α mRNA was lower after training ( P < 0.001). BNIP3 was lower after training in the 7°C than in the 20°C group ( P = 0.017) but not before training ( P = 0.549). No other differences occurred between temperature groups in VEGF, ERRα, NRF1, NRF2, TFAM, PINK1, Parkin, or BNIP3L mRNAs ( P > 0.05). PGC-1α protein and mtDNA were not different before training, after training, or between temperatures ( P > 0.05). Cycling power increased during the daily training ( P < 0.001) but was not different between temperatures ( P = 0.169). V̇o2peak increased with training ( P < 0.001) but was not different between temperature groups ( P = 0.460). These data indicate that a 3-wk period of acclimation/training in cold environmental temperatures alters PGC-1α gene expression acutely but this difference is not manifested in a greater increase in V̇o2peak and is dissipated as acclimation takes place. NEW & NOTEWORTHY This study examines the adaptive response of cellular signaling during exercise in cold environmental temperatures. We demonstrate that peroxisome proliferator-activated receptor-γ coactivator 1α mRNA is different between cold and room temperature environments before training but after training this difference no longer exists. This initial difference in transcriptional response between temperatures does not lead to differences in performance measures or increases in protein or mitochondria.

We tested the hypothesis that thermal behavior resulting in reductions in mean skin temperature alleviates thermal discomfort and mitigates the rise in core temperature during light-intensity exercise. In a 27 ± 0°C, 48 ± 6% relative humidity environment, 12 healthy subjects (6 men, 6 women) completed 60 min of recumbent cycling. In both trials, subjects wore a water-perfused suit top continually perfusing 34 ± 0°C water. In the behavior trial, subjects maintained their upper body thermally comfortable by pressing a button to perfuse cool water (2.2 ± 0.5°C) through the top for 2 min per button press. Metabolic heat production (control: 404 ± 52 W, behavior: 397 ± 65 W; P = 0.44) was similar between trials. Mean skin temperature was reduced in the behavior trial (by −2.1 ± 1.8°C, P < 0.01) because of voluntary reductions in water-perfused top temperature ( P < 0.01). Whole body ( P = 0.02) and local sweat rates were lower in the behavior trial ( P ≤ 0.05). Absolute core temperature was similar ( P ≥ 0.30); however, the change in core temperature was greater in the behavior trial after 40 min of exercise ( P ≤ 0.03). Partitional calorimetry did not reveal any differences in cumulative heat storage (control: 554 ± 229, behavior: 544 ± 283 kJ; P = 0.90). Thermal behavior alleviated whole body thermal discomfort during exercise (by −1.17 ± 0.40 arbitrary units, P < 0.01). Despite lower evaporative cooling in the behavior trial, similar heat loss was achieved by voluntarily employing convective cooling. Therefore, thermal behavior resulting in large reductions in skin temperature is effective at alleviating thermal discomfort during exercise without affecting whole body heat loss. NEW & NOTEWORTHY This study aimed to determine the effectiveness of thermal behavior in maintaining thermal comfort during exercise by allowing subjects to voluntarily cool their torso and upper limbs with 2°C water throughout a light-intensity exercise protocol. We show that voluntary cooling of the upper body alleviates thermal discomfort while maintaining heat balance through convective rather than evaporative means of heat loss.

High environmental temperatures are associated with increased risk of acute kidney injury, which may be related to reductions in renal blood flow. The susceptibility of the kidneys may be increased because of heat stress-induced changes in renal vascular resistance (RVR) to sympathetic activation. We tested the hypotheses that, compared with normothermia, increases in RVR during the cold pressor test (CPT, a sympathoexcitatory maneuver) are attenuated during passive heating and exacerbated after cooling recovery. Twenty-four healthy adults (22 ± 2 yr; 12 women, 12 men) completed CPTs at normothermic baseline, after passive heating to a rise in core temperature of ~1.2°C, and after cooling recovery when core temperature returned to ~0.2°C above normothermic baseline. Blood velocity was measured by Doppler ultrasound in the distal segment of the right renal artery (Renal, n = 24 during thermal stress, n = 12 during CPTs) or the middle portion of a segmental artery (Segmental, n = 12). RVR was calculated as mean arterial pressure divided by renal or segmental blood velocity. RVR increased at the end of CPT during normothermic baseline in both arteries (Renal: by 1.0 ± 1.0 mmHg·cm−1·s, Segmental: by 2.2 ± 1.2 mmHg·cm−1·s, P ≤ 0.03), and these increases were abolished with passive heating ( P ≥ 0.76). At the end of cooling recovery, RVR in both arteries to the CPT was restored to that of normothermic baseline ( P ≤ 0.17). These data show that increases in RVR to sympathetic activation during passive heating are attenuated and return to that of normothermic baseline after cooling recovery. NEW & NOTEWORTHY Our data indicate that increases in renal vascular resistance to the cold pressor test (i.e., sympathetic activation) are attenuated during passive heating, but at the end of cooling recovery this response returns to that of normothermic baseline. Importantly, hemodynamic responses were assessed in arteries going to (renal artery) and within (segmental artery) the kidney, which has not been previously examined in the same study during thermal and/or sympathetic stressors.

Myocardial mitochondrial biogenesis and vascular angiogenesis biomarker responses to postexercise cold-water immersion (CWI) have not been reported. Therefore, to determine those cardiac adaptations, adult male Sprague-Dawley rats were divided into three groups: postexercise CWI (CWI; n = 13), exercise only (Ex; n = 12), and untreated control (CON; n = 10). CWI and Ex were trained for 10 wk, 5 sessions/wk, 30–60 min/session. CWI rats were immersed after each session in cold water (15 min at ~12°C). CON remained sedentary. Left ventricle tissue was obtained 48 h after the last exercise session and analyzed for peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), vascular endothelial growth factor (VEGF), and heat shock protein 70 kDa (Hsp70) protein content and mRNA expression levels. In addition, superoxide dismutase activity and mRNA and malondialdehyde levels were evaluated. Ex and CWI induced higher PGC-1α protein content compared with CON (1.8 ± 0.6-fold, P < 0.001), which was significantly higher in CWI than Ex rats ( P = 0.01). VEGF protein (4.3 ± 3.7-fold) and mRNA (10.1 ± 1.1-fold) were markedly increased only in CWI ( P < 0.001) relative to CON. CWI and Ex augmented cardiac Hsp70 protein to a similar level relative to CON ( P < 0.05); however, Hsp70 mRNA increased only in Ex ( P = 0.002). No further differences were observed between groups. These results suggest that postexercise CWI may further enhance cardiac oxidative capacity by increasing the angiogenic and mitochondrial biogenic factors. In addition, CWI does not seem to worsen exercise-induced cardioprotection and oxidative stress. NEW & NOTEWORTHY A regular postexercise cold-water immersion for 10 wk of endurance training augmented the myocardial mitochondrial biogenesis and vascular angiogenesis coactivators peroxisome proliferator-activated receptor γ coactivator-1α and vascular endothelial growth factor, respectively. In addition, postexercise cold-water immersion did not attenuate the exercise-induced increase in the cardioprotective biomarker heat shock protein 70 kDa or increase exercise-induced oxidative stress.

Studies performed in controlled laboratory conditions have shown that environmental thermal application may induce various circulatory changes. We aimed to demonstrate the effect of local climate on hemodynamics according to echocardiography. Echocardiographic studies conducted in ambulatory patients, 18 yr of age or older, between January 2012 and July 2016, at our medical center, for whom climate data on the day of the echocardiogram study were available, were retrospectively included in case climate data. Discomfort index, apparent temperature, temperature-humidity index, and thermal index were computed. Echocardiograms conducted in hotter months (June–November) were compared with those done in colder months (December–May). The cohort consisted of 11,348 individuals, 46.2% women, and mean age of 57.9 ± 18.1 yr. Climate indexes correlated directly with stroke volume ( r = 0.039) and e′ (lateral r = 0.047; septal r = 0.038), and inversely with systolic pulmonary artery pressure (SPAP; r = −0.038) (all P values < 0.05). After adjustment for age and sex, echocardiograms conducted during June–November had a lower chance to show e′ septal < 7 cm/s (odds ratio 0.88, 95% confidence interval 0.78–0.98, P = 0.017) and SPAP > 40 mmHg (odds ratio 0.81, 95% confidence interval 0.67–0.99, P = 0.04) compared with those conducted in other months. The authors concluded that climate may affect hemodynamics, according to echocardiographic assessment in ambulatory patients. NEW & NOTEWORTHY In the present study, we examined 11,348 individuals who underwent ambulatory echocardiography. Analyses of the echocardiographic studies demonstrated that environmental thermal stress, i.e., climate, may affect hemodynamics. Most notably were the effects on diastolic function. Higher values of mitral e′, stroke volume, as well as ejection fraction, and lower values of systolic pulmonary artery pressure and tricuspid regurgitation were demonstrated on hotter days and seasons.

Reduced dexterity is a major problem in cold weather, with a need for a countermeasure that increases hand (Thand) and finger (Tfing) temperatures and improves dexterity. The purpose of this study was to determine whether electric heat (set point, 42°C) applied to the forearm (ARM, 82 W), face (FACE, 9.2 W), or combination of both (COMB, 91.2 W), either at the beginning of cold exposure (COLD; 0.5°C, 120 min; 2 clo insulation, seated, bare-handed) or after Tfing fell to 10.5°C [delayed trials (D)], improves Thand, Tfing, dexterity, and finger key pinch strength (Sfing). Volunteers ( n = 8; 26 ± 9 yr) completed 7 experimental trials in COLD: ARM, ARM-D, FACE, FACE-D, COMB, COMB-D, and no heating (CON). Temperatures were measured before (BASE) and throughout COLD. Tests of dexterity [Purdue Pegboard assembly (PP) and magazine loading (MAGLOAD)] and Sfing were measured at BASE and after 45 and 90 min of COLD. Data presented are at minute 90. Thand was warmer ( P < 0.001) during ARM (18.0 ± 2.6°C) and COMB (18.9 ± 2.0°C) versus CON (15.3 ± 1.5°C) and FACE (15.8 ± 1.5°C) for heating that was initiated at the beginning of COLD. Tfing was higher ( P < 0.04) during COMB (12.7 ± 5.1°C) versus CON (9.7 ± 2.1°C) and FACE (8.9 ± 2.2°C). The change from BASE for PP (no. of pieces) was less ( P < 0.005) in COMB (−4.5 ± 3.3) and ARM (−5.0 ± 6.0) versus CON (−13.0 ± 7.3) and FACE (−10.0 ± 8.3), and for MAGLOAD, it tended ( P = 0.06) to be less in COMB (−8.9 ± 6.2 cartridges) versus CON (−14.8 ± 3.7 cartridges). There was no change in Sfing from BASE (10.5 kg) to minute 90 in ARM or COMB (0.7 ± 1.4 and −0.2 ± 1.7 kg, respectively) but a decrease ( P < 0.01) in CON and FACE (−2.1 ± 2.0 and −1.6 ± 1.9 kg, respectively). There were no differences in Thand, Tfing, dexterity, and Sfing at minute 90 when comparing heating that was initiated at the beginning of COLD versus delayed heating. In conclusion, heating using either COMB or ARM, compared with CON and FACE, improved Thand and Tfing and reduced the decline in dexterity by 20%–50% and Sfing by 90%. Furthermore, delayed heating had no deleterious effect on Thand, Tfing, dexterity, and Sfing compared with heating that started at the beginning of cold exposure. NEW & NOTEWORTHY The present study demonstrated that, during sedentary cold air exposure, localized heating that was applied from the beginning of cold exposure on the forearm increases hand and finger temperatures and finger strength, leading to subsequent improvements in manual dexterity. In addition, localized heating that was delayed until finger temperatures cooled significantly also caused higher peripheral temperatures, leading to better strength and manual dexterity, compared with no heating.

The ability of hands and feet to convey skin thermal sensations is an important contributor to our experience of the surrounding world. Surprisingly, the detailed topographical distribution of warm and cold thermosensitivity across hands and feet has not been mapped, although sensitivity maps exist for touch and pain. Using a recently developed quantitative sensory test, we mapped warm and cold thermosensitivity of 103 skin sites over glabrous and hairy skin of hands and feet in male (M; 30.2 ± 5.8 yr) and female (F; 27.7 ± 5.1 yr) adults matched for body surface area (M: 1.77 ± 0.2 m2; F: 1.64 ± 0.1 m2; P = 0.155). Findings indicated that warm and cold thermosensitivity varies by fivefold across glabrous and hairy skin of hands and feet and that hands (warm/cold sensitivity: 1.25/2.14 vote/°C) are twice as sensitive as the feet (warm/cold sensitivity: 0.51/0.99 vote/°C). Opposite to what is known for touch and pain sensitivity, we observed a characteristic distal-to-proximal increase in thermosensitivity over both hairy and glabrous skin (i.e., from fingers and toes to body of hands and feet), and found that hairy skin is more sensitive than glabrous. Finally, we show that body surface area-matched men and women presented small differences in thermosensitivity and that these differences are constrained to glabrous skin only. Our high-density thermosensory micromapping provides the most detailed thermosensitivity maps of hands and feet in young adults available to date. These maps offer a window into peripheral and central mechanisms of thermosensory integration in humans and will help guide future developments in smart skin and sensory neuroprostheses, in wearable, energy-efficient personal comfort systems, and in sport and protective clothing. NEW & NOTEWORTHY We provide the most detailed thermosensitivity maps across glabrous and hairy skin of hands and feet in men and women available to date. Our maps show that thermosensitivity varies by fivefold across hands and feet, distal regions (e.g., fingers, toes) are less sensitive than proximal (e.g., palm, sole), hands are twice as sensitive as feet, and men and women present small thermosensitivity differences. These findings will help guide developments in sensory neuroprostheses, wearable comfort systems, and sport/protective clothing.

Humans with a patent foramen ovale (PFO) have a higher esophageal temperature (Tesoph) than humans without a PFO (PFO−). Thus the presence of a PFO might also be associated with differences in thermal responsiveness to passive cooling and heating such as shivering and hyperpnea, respectively. The purpose of this study was to determine whether thermal responses to passive cooling and heating are different between PFO− subjects and subjects with a PFO (PFO+). We hypothesized that compared with PFO− subjects PFO+ subjects would cool down more rapidly and heat up slower and that PFO+ subjects who experienced thermal hyperpnea would have a blunted increase in ventilation. Twenty-seven men (13 PFO+) completed two trials separated by >48 h: 1) 60 min of cold water immersion (19.5 ± 0.9°C) and 2) 30 min of hot water immersion (40.5 ± 0.2°C). PFO+ subjects had a higher Tesoph before and during cold water and hot water immersion ( P < 0.05). However, the rate of temperature change was similar between groups for each condition. Within a subset of 18 subjects (8 PFO+) who experienced thermal hyperpnea, PFO+ subjects experienced thermal hyperpnea at a higher absolute Tesoph but with a blunted magnitude compared with PFO− subjects. These data suggest that PFO+ subjects have a higher Tesoph at rest and have blunted thermal hyperpnea during passive heating. NEW & NOTEWORTHY Patent foramen ovale (PFO) is found in ~25–40% of the population. The presence of a PFO appears to be associated with a greater core body temperature and blunted ventilatory responses during passive heating. The reason for this blunted ventilatory response to passive heating is unknown but may suggest differences in thermal sensitivity in PFO+ subjects compared with PFO− subjects.

During moderate cold exposure, cardiovascular-related morbidity and mortality increase disproportionately in hypertensive adults (HTN); however, the mechanisms underlying this association are not well defined. We hypothesized that whole body cold stress would evoke exaggerated increases in blood pressure (BP) and muscle sympathetic nerve activity (MSNA) in HTN compared with normotensive adults (NTN) and that sympathetic baroreflex function would be altered during cooling in HTN. MSNA (peroneal microneurography) and beat-to-beat BP (Finometer) were measured continuously in 10 NTN (6 men/4 women; age 53 ± 3 yr; resting BP 125 ± 3/79 ± 1 mmHg) and 13 HTN (7 men/6 women; age 58 ± 2 yr; resting BP 146 ± 5/88 ± 2 mmHg) during whole body cooling-induced reductions in mean skin temperature (Tsk; water-perfused suit) from 34.0 to 30.5°C. During cooling, the increase in mean arterial pressure was greater in HTN (NTN: Δ6 ± 2 vs. HTN: Δ11 ± 1 mmHg; P = 0.02) and accompanied by exaggerated increases in MSNA (NTN: Δ8 ± 3 vs. HTN: Δ20 ± 3 bursts/100 heart beats; P < 0.01). The slope of the relation between MSNA and diastolic BP did not change during cooling in NTN (Tsk 34.0°C: −4.4 ± 0.8 vs. Tsk 30.5°C: −5.0 ± 0.3 bursts·100 heart beats−1·mmHg−1; P = 0.47) but increased in HTN (Tsk 34.0°C: −3.6 ± 0.4 vs. Tsk 30.5°C: −5.4 ± 0.4 bursts·100 heart beats)−1·mmHg−1; P = 0.02). These findings demonstrate that the cooling-induced increases in BP and MSNA are exaggerated in HTN. Furthermore, during cooling, sympathetic baroreflex sensitivity increases in HTN, but not NTN, presumably to allow for baroreflex-mediated buffering of excessive cooling-induced increases in BP. Collectively, these findings suggest that sympathetic function is altered during whole body cooling in hypertension. NEW & NOTEWORTHY These novel findings demonstrate that whole body cooling-induced reductions in mean skin temperature elicited greater increases in blood pressure and muscle sympathetic nerve activity in hypertensive adults. In addition, during moderate cold exposure, sympathetic baroreflex sensitivity increased in hypertensive, but not normotensive, adults.

Mechanisms mediating postexercise cold-induced increases in PGC-1α gene expression in human skeletal muscle are yet to be fully elucidated but may involve local cooling effects on AMPK and p38 MAPK-related signaling and/or increased systemic β-adrenergic stimulation. Therefore, we aimed to examine whether postexercise cold water immersion enhancement of PGC-1α mRNA is mediated through local or systemic mechanisms. Ten subjects completed acute cycling (8 × 5 min at ~80% peak power output) followed by seated-rest (CON) or single-leg cold water immersion (CWI; 10 min, 8°C). Muscle biopsies were obtained preexercise, postexercise, and 3 h postexercise from a single limb in the CON condition but from both limbs in CWI [thereby providing tissue from a CWI and nonimmersed limb (NOT)]. Muscle temperature decreased up to 2 h postexercise following CWI (−5°C) in the immersed limb, with lesser changes observed in CON and NOT (−3°C, P < 0.05). No differences between limbs were observed in p38 MAPK phosphorylation at any time point ( P < 0.05), whereas a significant interaction effect was present for AMPK phosphorylation ( P = 0.031). Exercise (CON) increased gene expression of PGC-1α 3 h postexercise (~5-fold, P < 0.001). CWI augmented PGC-1α expression above CON in both the immersed (CWI; ~9-fold, P = 0.003) and NOT limbs (~12-fold, P = 0.001). Plasma normetanephrine concentration was higher in CWI vs. CON immediately postimmersion (860 vs. 665 pmol/l, P = 0.034). We report for the first time that local cooling of the immersed limb evokes transcriptional control of PGC-1α in the nonimmersed limb, suggesting increased systemic β-adrenergic activation of AMPK may mediate, in part, postexercise cold induction of PGC-1α mRNA. NEW & NOTEWORTHY We report for the first time that postexercise cold water immersion of one limb also enhances PGC-1α expression in a contralateral, nonimmersed limb. We suggest that increased systemic β-adrenergic stimulation, and not localized cooling per se, exerts regulatory effects on local signaling cascades, thereby modulating PGC-1α expression. Therefore, these data have important implications for research designs that adopt contralateral, nonimmersed limbs as a control condition while also increasing our understanding of the potential mechanisms underpinning cold-mediated PGC-1α responses.

The objective of this study was to investigate the impacts of different stresses on time-varying autonomic reactivity and cardiovascular coupling. In total, 25 male subjects were recruited. RR intervals (RRI), systolic and diastolic blood pressure (SBP, DBP), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) values were collected during rest, mental arithmetic task (MAT), and cold pressor test (CPT). Baroreflex sensitivity (BRS) was derived using the transfer function method. Continuous wavelet transformation of RRI was used to describe the time-variant patterns of autonomic neural activities. Wavelet cross correlation and phase synchronization were used to estimate the amplitude and phase coupling between RRI and SBP. MAT was characterized by increased heart rate (HR), SBP, DBP, and CO with decreased BRS attributable to prolonged parasympathetic withdrawal. Moreover, cardiovascular coupling was disrupted in MAT. These results indicated that baroreflex was depressed, and the top-down system started to take action under mental stress. In CPT, SBP, DBP, and SVR increased significantly, whereas HR and BRS remained unchanged. The increase of sympathetic activity was transient, and cardiovascular coupling did not change in CPT. Intriguingly, the frequency of the maximum cross-correlation coefficient in the low-frequency band (0.04–0.15 Hz) was significantly decreased in CPT, which may be due to the change of resonance frequency of the baroreflex loop. NEW & NOTEWORTHY The study is the first to compare the time-variant pattern of autonomic nervous activities and cardiovascular coupling between the mental arithmetic task (MAT) and the cold pressor test (CPT). Our results demonstrated that MAT and CPT elicited different time-varying patterns of autonomic neural activities and cardiovascular synchronization. Both the amplitude and phase consistency of blood pressure and heart rate decreased in MAT. CPT may affect the harmonic frequency of the baroreflex loop.

Because the majority of cold exposure studies are constrained to short-term durations of several hours, the long-term metabolic demands of cold exposure, such as during survival situations, remain largely unknown. The present study provides the first estimates of thermogenic rate, oxidative fuel selection, and muscle recruitment during a 24-h cold-survival simulation. Using combined indirect calorimetry and electrophysiological and isotopic methods, changes in muscle glycogen, total carbohydrate, lipid, protein oxidation, muscle recruitment, and whole body thermogenic rate were determined in underfed and noncold-acclimatized men during a simulated accidental exposure to 7.5°C for 12 to 24 h. In noncold-acclimatized healthy men, cold exposure induced a decrease of ∼0.8°C in core temperature and a decrease of ∼6.1°C in mean skin temperature (range, 5.4-6.9°C). Results showed that total heat production increased by approximately 1.3- to 1.5-fold in the cold and remained constant throughout cold exposure. Interestingly, this constant rise in Ḣprod and shivering intensity was accompanied by a large modification in fuel selection that occurred between 6 and 12 h; total carbohydrate oxidation decreased by 2.4-fold, and lipid oxidation doubled progressively from baseline to 24 h. Clearly, such changes in fuel selection dramatically reduces the utilization of limited muscle glycogen reserves, thus extending the predicted time to muscle glycogen depletion to as much as 15 days rather than the previous estimates of approximately 30–40 h. Further research is needed to determine whether this would also be the case under different nutritional and/or colder conditions.

The vascular response to local skin cooling is dependent in part on a cold-induced translocation of α2C-receptors and an increased α-adrenoreceptor function. To discover whether β-adrenergic function might contribute, we examined whether β-receptor sensitivity to the β-agonist isoproterenol was affected by local skin temperature. In seven healthy volunteers, skin blood flow was measured from the forearm by laser-Doppler flowmetry and blood pressure was measured by finger photoplethysmography. Data were expressed as cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial blood pressure). Pharmacological agents were administered via intradermal microdialysis. We prepared four skin sites: one site was maintained at a thermoneutral temperature of 34°C (32 ± 10%CVCmax) one site was heated to 39°C (38 ± 11%CVCmax); and two sites were cooled, one to 29°C (22 ± 7%CVCmax) and the other 24°C (16 ± 4%CVCmax). After 20 min at these temperatures to allow stabilization of skin blood flow, isoproterenol was perfused in concentrations of 10, 30, 100, and 300 μM. Each concentration was perfused for 15 min. Relative to the CVC responses to isoproterenol at the thermoneutral skin temperature (34°C) (+21 ± 10%max), low skin temperatures reduced (at 29°C) (+17 ± 6%max) or abolished (at 24°C) (+1 ± 5%max) the vasodilator response, and warm (39°C) skin temperatures enhanced the vasodilator response (+40 ± 9%max) to isoproterenol. These data indicate that β-adrenergic function was influenced by local skin temperature. This finding raises the possibility that a part of the vasoconstrictor response to direct skin cooling could include reduced background β-receptor mediated vasodilation.

Sensing skin wetness is linked to inputs arising from cutaneous cold-sensitive afferents. As thermosensitivity to cold varies significantly across the torso, we investigated whether similar regional differences in wetness perception exist. We also investigated the regional differences in thermal pleasantness and whether these sensory patterns are influenced by ambient temperature. Sixteen males (20 ± 2 yr) underwent a quantitative sensory test under thermo-neutral [air temperature (Tair) = 22°C; relative humidity (RH) = 50%] and warm conditions (Tair = 33°C; RH = 50%). Twelve regions of the torso were stimulated with a dry thermal probe (25 cm2) with a temperature of 15°C below local skin temperature (Tsk). Variations in Tsk, thermal, wetness, and pleasantness sensations were recorded. As a result of the same cold-dry stimulus, the skin-cooling response varied significantly by location ( P = 0.003). The lateral chest showed the greatest cooling (−5 ± 0.4°C), whereas the lower back showed the smallest (−1.9 ± 0.4°C). Thermal sensations varied significantly by location and independently from regional variations in skin cooling with colder sensations reported on the lateral abdomen and lower back. Similarly, the frequency of perceived skin wetness was significantly greater on the lateral and lower back as opposed to the medial chest. Overall wetness perception was slightly higher under warm conditions. Significantly more unpleasant sensations were recorded when the lateral abdomen and lateral and lower back were stimulated. We conclude that humans present regional differences in skin wetness perception across the torso, with a pattern similar to the regional differences in thermosensitivity to cold. These findings indicate the presence of a heterogeneous distribution of cold-sensitive thermo-afferent information.

Cardiovascular mortality increases in cold weather in older adults, and physical activity may impart even greater cardiovascular risk than cold exposure alone. Human aging is associated with exaggerated pressor responses to whole body cooling; however, the sympathetic response to cold stress alone and in combination with isometric exercise is unknown. We hypothesized that cold stress would 1) increase muscle sympathetic nerve activity (MSNA) and 2) augment the MSNA response to isometric handgrip in older adults. Whole body cooling (water-perfused suit) was conducted in 11 young (23 ± 1 yr) and 12 healthy older adults (60 ± 2 yr). Blood pressure (BP; Finometer) and MSNA (microneurography) were measured throughout cooling and during isometric handgrip at 30% maximal voluntary contraction performed at a mean skin temperature (Tsk) of 34 and 30.5°C. MSNA was greater in older adults at Tsk = 34.0°C and throughout cooling ( P < 0.05). MSNA increased during cooling in older, but not young, adults (young: Δ0 ± 1 vs. older: Δ8 ± 1 bursts/min; P < 0.05). The cooling-induced increase in BP was greater in older adults ( P < 0.05). During handgrip, the increases in MSNA and BP were not different between conditions in either young (Δ14 ± 2 Tsk 34°C vs. Δ12 ± 3 Tsk 30.5°C bursts/min; Δ20 ± 3 Tsk 34°C vs. Δ19 ± 3 Tsk 30.5°C mmHg; both P > 0.05) or older adults (Δ12 ± 1 Tsk 34°C vs. Δ8 ± 1 Tsk 30.5°C bursts/min; Δ18 ± 3 Tsk 34°C vs. Δ17 ± 2 Tsk 30.5°C mmHg; both P > 0.05). In summary, MSNA increased during cold stress in older, but not young, adults. Furthermore, concomitant cold stress did not alter the sympathetic responses to isometric exercise in either age group, suggesting preserved sympathetic responsiveness during exercise in the cold in healthy aging.

The purpose of this study was to examine the effect of β-hydroxy-β-methylbutyrate-free acid (HMB-FA) and cold-water immersion (CWI) on circulating concentrations of TNF-α and monocyte TNF-α receptor 1 (TNFR1) expression. Forty resistance-trained men (22.3 ± 2.4 yr) were randomized into four groups [placebo (PL), HMB-FA, CWI, and HMB-FA-CWI] and performed an acute, intense exercise protocol (four sets of up to 10 repetitions of the squat, dead lift, and split squat). Participants also performed four sets of up to 10 repetitions of the squat at 24 and 48 h following the initial exercise bout. Blood was sampled before exercise (PRE), immediately postexercise (IP), and 30 min, 24 h, and 48 h postexercise (30P, 24P, and 48P, respectively). Circulating TNF-α was assayed, and TNFR1 expression on CD14+ monocytes was measured by flow cytometry. The exercise protocol significantly elevated TNF-α in only PL ( P = 0.006) and CWI ( P = 0.045) IP. Mean percent changes show that TNF-α significantly increased from PRE to IP for only PL and CWI groups ( P < 0.05), whereas the percent change of TNF-α for HMB-FA and HMB-FA-CWI was not significant. TNFR1 expression was elevated in PL ( P = 0.023) and CWI ( P = 0.02) at 30P compared with PRE, whereas both HMB-FA-treated groups did not increase significantly. In conclusion, HMB-FA attenuated circulating TNF-α IP and TNFR1 expression during recovery compared with PL and CWI. HMB-FA supplementation may attenuate the initial immune response to intense exercise, which may reduce recovery time following intense exercise.

Tactile stimulation of the oropharynx (TSO) elicits the gag reflex and increases heart rate (HR) and mean arterial pressure (MAP) in anesthetized patients. However, the interaction between upper-airway defense reflexes and the sympathetic nervous system has not been investigated in conscious humans. In Experiment 1, beat-by-beat measurements of HR, MAP, muscle sympathetic nerve activity (MSNA), and renal vascular resistance (RVR) were measured during TSO and tactile stimulation of the hard palate (Sham) in the supine posture. In Experiment 2, TSO was performed before (pre) and after (post) inhalation of 4% lidocaine via nebulizer. Rate pressure product (RPP) was determined. Compared with Sham, TSO elicited the gag reflex and increased RPP [absolute change (Δ)36 ± 6 vs. 17 ± 5%], MSNA (Δ122 ± 39 vs. 19 ± 19%), and RVR (Δ55 ± 11 vs. 4 ± 4%). This effect occurred within one to two cardiac cycles of TSO. The ΔMAP (12 ± 3 vs. 6 ± 1 mmHg) and the ΔHR (10 ± 3 vs. 3 ± 3 beats/min) were also greater following TSO compared with Sham. Lidocaine inhalation blocked the gag reflex and attenuated increases in MAP (Δpre: 16 ± 2; Δpost: 5 ± 2 mmHg) and HR (Δpre: 12 ± 3; Δpost: 2 ± 2 beats/min) in response to TSO. When mechanically stimulated, afferents in the oropharynx not only serve to protect the airway but also cause reflex increases in MSNA, RVR, MAP, and HR. An augmented sympathoexcitatory response during intubation and laryngoscopy may contribute to perioperative cardiovascular morbidity and mortality.

The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold + grip protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial function (tissue Doppler imaging), O2 saturation, and pulmonary function were measured. The rate-pressure product (RPP) was used as an index of myocardial O2 demand, whereas CBV was used as an index of myocardial O2 supply. Compared with the sham protocol, the cold air protocol caused a significantly higher RPP, but there was a significant reduction in CBV. The cold + grip protocol caused a significantly greater increase in RPP compared with the grip protocol ( P = 0.045), but the increase in CBV was significantly less ( P = 0.039). However, myocardial function was not impaired during the cold + grip protocol relative to the grip protocol alone. Collectively, these data indicate that there is a supply-demand mismatch in the coronary vascular bed when cold ambient air is breathed during acute exertion but myocardial function is preserved, suggesting an adequate redistribution of blood flow.

The relationship between exercise performance and lactate and ventilatory thresholds under two distinct environmental conditions is unknown. We examined the relationships between six lactate threshold methods (blood- and ventilation-based) and exercise performance in cyclists in hot and cool environments. Twelve cyclists performed a lactate threshold test, a maximal O2 uptake (V̇o2max) test, and a 1-h time trial in hot (38°C) and cool (13°C) conditions, before and after heat acclimation. Eight control subjects completed the same tests before and after 10 days of identical exercise in a cool environment. The highest correlations were observed with the blood-based lactate indexes; however, even the indirect ventilation-based indexes were well correlated with mean power during the time trial. Averaged bias was 15.4 ± 3.6 W higher for the ventilation- than the blood-based measures ( P < 0.05). The bias of blood-based measures in the hot condition was increased: the time trial was overestimated by 37.7 ± 3.6 W compared with only 24.1 ± 3.2 W in the cool condition ( P < 0.05). Acclimation had no effect on the bias of the blood-based indexes ( P = 0.51) but exacerbated the overestimation by some ventilation-based indexes by an additional 34.5 ± 14.1 W ( P < 0.05). Blood-based methods to determine lactate threshold show less bias and smaller variance than ventilation-based methods when predicting time-trial performance in cool environments. Of the blood-based methods, the inflection point between steady-state lactate and rising lactate (INFL) was the best method to predict time-trial performance. Lastly, in the hot condition, ventilation-based predictions are less accurate after heat acclimation, while blood-based predictions remain valid in both environments after heat acclimation.

A positive inotropic action by the sympathetic nervous system on skeletal muscles has been observed and investigated in animal and in vitro studies. This action provided a theoretical basis for the putative ergogenic action of catecholamines and adrenergic agonists, although there is no clear evidence of this effect in humans. The aim of this study was to investigate the occurrence of inotropic effects associated to physiological sympathetic activation in healthy subjects. The muscle force capacity was investigated in the tibialis anterior ( n = 9 subjects) and in the soleus ( n = 9) muscles electrically stimulated with single pulses and double pulses with variable interspike interval (4–1,000 ms) and short pulse trains (frequency: 5–14 Hz) before, during, and after sympathetic activation by the cold pressor test (CPT). CPT significantly decreased by 10.4 ± 7.2 and 10.6 ± 4.4% the force produced by single and double pulse stimulation, respectively, and produced smaller decreases in the force obtained by train stimulation in the tibialis anterior, while no significant changes were observed in either type of contraction in the soleus muscle. CPT failed to induce any increase in the force capacity of the investigated muscles. The prevalent decrease in force evidenced in this study supports the concept that the weakening sympathetic action on type I fiber, already shown to occur in humans, prevails over the putative potentiating action.

Our aim was to investigate the effects of acute cold pressor test (CPT) on augmentation index (AI) and wave intensity (WI) indexes from right common carotid artery (RCCA) and right common femoral artery (RCFA) and to test whether the reflection coefficient (RC) from wave intensity analysis can reflect the distal vascular resistance (DVR) accurately. Forty-three healthy males were randomly selected for measurements at baseline and 1 min after CPT at RCCA or RCFA. CPT induced similar increases of heart rate and blood pressure in RCCA and RCFA groups with their pulse pressures unchanged. The W2 (the second peak of WI) was too obscure in RCFA to be analyzed. The W1 (the first peak of WI) of both arteries, W1-W2 (interval between W1 and W2), and NA (negative area between W1 and W2, indicating reflected waves) of RCCA and the R-W1 (interval between the R wave of ECG and W1) of RCFA decreased obviously, whereas the W2 and R-W1 of RCCA and the RC (calculated as NA/W1) of RCFA increased with no changes in the RC of RCCA and the NA of RCFA during CPT compared with baseline. The AIs from both arteries increased significantly after CPT. These results suggested that acute CPT has opposing effects on cerebral and peripheral vascular resistances, with the former decreased and the latter increased. The RCs from RCCA and RCFA are more associated with the changes of cerebral and peripheral vascular resistances, respectively, than the NA and AI, and the RC is of guiding value in assessing DVR.

One of the factors limiting the oxidation of exogenous glucose during cold exposure may be the delay in establishing a shivering steady state (approximately 60 min), reducing glucose uptake into skeletal muscle. Therefore, using indirect calorimetry and isotopic methodologies in non-cold-acclimatized men, the main purpose of this study was to determine whether ingesting glucose at a moment coinciding with the maximal shivering intensity could increase the utilization rate of the ingested glucose. (13)C-enriched glucose was ingested (800 mg/min) from the onset (G0) or after 60 min (G60) of cold exposure when the thermogenic rate was stabilized to low-intensity shivering (approximately 2.5 times resting metabolic rate). For the same quantity of glucose ingested, the oxidation rate of exogenous glucose was 35% higher in G60 (159+/-17 vs. 118+/-17 mg/min in G0) between minutes 60 and 90. By the end of cold exposure, exogenous glucose oxidation was significantly greater in G0, reaching 231+/-14 mg/min, approximately 15% higher than the only rates previously reported. This considerably reduced the utilization of endogenous reserves over time and compared with the G60 condition. This study also demonstrates a fall in muscle glycogen utilization, when glucose was ingested from the onset of cold exposure (from approximately 150 to approximately 75 mg/min). Together, these findings indicate the importance of ingesting glucose immediately on exposure to a cold condition, relying on shivering thermogenesis and sustaining that consumption for as long as possible. This substrate not only provides an auxiliary fuel source for shivering thermogenesis, but, more importantly, preserves the limited endogenous glucose reserves.

Hypoxia decreases core body temperature in animals and humans during cold exposure. In addition, hypoxia increases skin blood flow in thermoneutral conditions, but the impact of hypoxic vasodilation on vasoconstriction during cold exposure is unknown. In this study, skin blood flow was assessed using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated as red blood cell flux/mean arterial pressure and normalized to baseline ( n = 7). Subjects were exposed to four different conditions in the steady state (normoxia and poikilocapnic, isocapnic, and hypercapnic hypoxia) and were cooled for 10 min using a water-perfused suit in each condition. CVC increased during all three hypoxic exposures (all P < 0.05 vs. baseline), and the magnitude of these steady-state responses was not affected by changes in end-tidal CO2 levels. During poikilocapnic and hypercapnic hypoxia, cold exposure reduced CVC to the same levels observed during normoxic cooling ( P > 0.05 vs. normoxia), whereas CVC remained elevated throughout cold exposure during isocapnic hypoxia ( P < 0.05 vs. normoxia). The magnitude of vasoconstriction during cold stress was similar in all conditions ( P > 0.05). Thus the magnitude of cutaneous vasodilation during steady-state hypoxia is not affected by CO2 responses. In addition, the magnitude of reflex vasoconstriction is not altered by hypoxia, such that the upward shift in skin blood flow (hypoxic vasodilation) is maintained during whole body cooling.

Cardiovascular-related mortality peaks during cold winter months, particularly in older adults. Acute physiological responses, such as increases in blood pressure, in response to cold exposure may contribute to these associations. To determine whether the blood pressure-raising effect (pressor response) of non-internal body temperature-reducing cold stress is greater with age, we measured physiological responses to 20 min of superficial skin cooling, via water-perfused suit, in 12 younger [25 ± 1 (SE) yr old] and 12 older (65 ± 2 yr old) adults. We found that superficial skin cooling elicited an increase in blood pressure from resting levels (pressor response; P < 0.05) in younger and older adults. However, the magnitude of this pressor response (systolic and mean blood pressure) was more than twofold higher in older adults ( P < 0.05 vs. younger adults). The magnitude of the pressor response was similar at peripheral (brachial) and central (estimated in the aorta) measurement sites. Regression analysis revealed that aortic pulse wave velocity, a measure of central arterial stiffness obtained before cooling, was the best predictor of the increased pressor response to superficial skin cooling in older adults, explaining ∼63% of its variability. These results indicate that there is a greater pressor response to non-internal body temperature-reducing cold stress with age in humans that may be mediated by increased levels of central arterial stiffness.

We examined the effect of thermal balance perturbation on cold-induced vasodilation through a dynamic A-B-A-B design applying heat (condition A) and cold (condition B) to the body's core, while the hand is exposed to a stable cold stimulus. Fifteen healthy adults (8 men, 7 women) volunteered. Applications of heat and cold were achieved through water immersions in two tanks maintained at 42 and 12 degrees C water temperature, respectively, in an A-B-A-B fashion. Throughout the experiment, the participants' right hand up to the ulnar styloid process was placed inside a temperature-controlled box set at 0 degrees C air temperature. Results demonstrated that cold-induced vasodilation occurred only during condition B and at times when body heat content was decreasing but rectal temperature had not yet dropped to baseline levels. Following the occurrence of all cold-induced vasodilation events, rectal temperature was reduced, and the phenomenon ceased when rectal temperature fell below baseline. Heart rate variability data obtained before and during cold-induced vasodilation demonstrated a shift of autonomic interaction toward parasympathetic dominance, which, however, was attributed to a sympathetic withdrawal. Receiver operating characteristics curve analyses demonstrated that the cold-induced vasodilation onset cutoff points for rectal temperature change and finger temperature were 0.62 and 16.76 degrees C, respectively. It is concluded that cold-induced vasodilation is a centrally originating phenomenon caused by sympathetic vasoconstrictor withdrawal. It is dependent on excess heat, and it may be triggered by excess heat with the purpose of preserving thermal balance.

Immersion pulmonary edema (IPE) is a condition with sudden onset in divers and swimmers suspected to be due to pulmonary arterial or venous hypertension induced by exercise in cold water, although it does occur even with adequate thermal protection. We tested the hypothesis that cold head immersion could facilitate IPE via a reflex rise in pulmonary vascular pressure due solely to cooling of the head. Ten volunteers were instrumented with ECG and radial and pulmonary artery catheters and studied at 1 atm absolute (ATA) during dry and immersed rest and exercise in thermoneutral (29-31 degrees C) and cold (18-20 degrees C) water. A head tent varied the temperature of the water surrounding the head independently of the trunk and limbs. Heart rate, Fick cardiac output (CO), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), and central venous pressure (CVP) were measured. MPAP, PAWP, and CO were significantly higher in cold pool water (Por = 0.004). Resting MPAP and PAWP values (means +/- SD) were 20 +/- 2.9/13 +/- 3.9 (cold body/cold head), 21 +/- 3.1/14 +/- 5.2 (cold/warm), 14 +/- 1.5/10 +/- 2.2 (warm/warm), and 15 +/- 1.6/10 +/- 2.6 mmHg (warm/cold). Exercise values were higher; cold body immersion augmented the rise in MPAP during exercise. MAP increased during immersion, especially in cold water (P0.0001). Except for a transient additive effect on MAP and MPAP during rapid head cooling, cold water on the head had no effect on vascular pressures. The results support a hemodynamic cause for IPE mediated in part by cooling of the trunk and extremities. This does not support the use of increased head insulation to prevent IPE.

Hypertensive (HTN) animal models demonstrate lower venous compliance as well as increased venous tone and responsiveness compared with normotensive (NTN) controls. However, the extent to which findings in experimental animals can be extended to humans is unknown. Forearm and calf venous compliance were quantified in 9 NTN (23 ± 1 yr) and 9 HTN (24 ± 1 yr) men at baseline, after administration of nitroglycerin (NTG), during a cold pressor test (CP), and post-handgrip exercise ischemia (PEI). Individual pressure-volume relationships from a cuff deflation protocol (1 mmHg/s) were modeled with a quadratic regression. Regression parameters β1 and β2 were used to calculate compliance. A one-way ANOVA was used to compare the beta parameters and a repeated-measures ANOVA was used to compare volumes across all pressures (between groups at baseline and within groups during perturbations). Limb venous compliance was similar between groups (forearm: NTN β1 = 0.11 ± 0.01 and β2 = −0.00097 ± 0.0001, HTN β1 = 0.10 ± 0.01 and β2 = −0.00088 ± 0.0001; calf: NTN β1 = 0.12 ± 0.01 and β2 = −0.00102 ± 0.0001, HTN β1 = 0.11 ± 0.01 and β2 = −0.00090 ± 0.0001). However, at baseline, volume across all pressures (i.e., capacitance) was lower in the forearm ( P ≤ 0.01) and tended to be lower in the calf ( P = 0.08) in HTN subjects. Venous compliance was not altered by any perturbation in either group. Forearm volume was increased during NTG in HTN subjects only. While venous compliance was similar between NTN and HTN adults, HTN adults have lower forearm venous capacitance (volume) which is increased with NTG. These data suggest that young HTN adults may have augmented venous smooth muscle tone compared with NTN controls.

The purpose of this study was to examine the effectiveness of reducing core temperature in postexercise hyperthermic subjects and to assess if hand cooling (HC) improves subsequent timed distance performance. Following a detailed measurement check on the use of insulated auditory canal temperature (Tac), eight wheelchair (WA) athletes and seven male able-bodied (AB) athletes performed two testing sessions, comprising a 60-min exercise protocol and 10-min recovery period, followed by a performance trial (1 km and 3 km for WA and AB, respectively) at 30.8°C (SD 0.2) and 60.6% (SD 0.2) relative humidity. In a counterbalanced order, HC and a no-cooling condition was administered during the 10-min recovery period before the performance trial. Nonsignificant condition × time interactions for both WA ( F15,75= 1.5, P = 0.14) and AB ( F15,90= 1.2, P = 0.32) confirmed that the exercise-induced changes (Δ) in Tacwere similar before each intervention. However, the exercise-induced increase was evidently greater in AB compared with WA (2.0 vs. 1.3°C change, respectively). HC produced ΔTacof −0.4°C (SD 0.4) and −1.2°C (SD 0.2) in comparison (WA and AB, respectively), and simple-effects analyses suggested that the reductions in Tacwere noteworthy after 4 min of HC. HC had an impact on improving AB performances by −4.0 s (SD 11.5) ( P < 0.05) and WA by −20.5 s (SD 24.2) ( P > 0.05). In conclusion, extraction of heat through the hands was effective in lowering Tacin both groups and improving 3-km performance in the AB athletes and trends toward positive gains for the 1-km performance times of the WA group.

The purpose of the present study was to determine whether ultrasound is a useful tool to measure the venous characteristics of the lower extremity during a standard venous collecting cuff deflation protocol. To accomplish this, lower extremity pressure-cross-sectional area (CSA) and pressure-volume relationships were measured in eight (25 ± 1 yr) supine subjects. Popliteal vein CSA was assessed by using high-resolution ultrasound, while calf volume changes were simultaneously assessed by using venous occlusion plethysmography (VOP). Pressure-CSA and pressure-volume relationships were assessed at baseline, during the cold pressor (CP) test, and following sublingual nitroglycerin (NTG) administration. Relationships were modeled with a quadratic regression equation, and β1 and β2 were used as indexes of venous compliance. Popliteal vein regression parameters β1 (8.485 ± 2.616 vs. 7.638 ± 2.664, baseline vs. CP; 8.485 ± 2.616 vs. 7.734 ± 3.076, baseline vs. NTG; both P > 0.05) and β2 (−0.0841 ± 0.0241 vs. −0.0793 ± 0.0242, baseline vs. CP; −0.0841 ± 0.0241 vs. −0.0771 ± 0.0280, baseline vs. NTG; both P > 0.05) were not affected by CP or NTG. Similarly, calf regression parameters β1 and β2, obtained with VOP, were not altered during either trial. Intraclass correlations for venous compliance assessed with ultrasound and VOP were 0.92 and 0.97, respectively, indicating acceptable reproducibility. These data suggest that ultrasound is a functional and reproducible tool to assess the venous characteristics of the lower extremity, in addition to VOP. Additionally, popliteal vein and calf compliance were not affected by the CP test or NTG.

Cold thermoregulatory models (CTM) have primarily been developed to predict core temperature (Tcore) responses during sedentary immersion. Few studies have examined their efficacy to predict Tcore during exercise cold exposure. The purpose of this study was to compare observed Tcore responses during exercise in cold water with the predicted Tcore from a three-cylinder (3-CTM) and a six-cylinder (6-CTM) model, adjusted to include heat production from exercise. A matrix of two metabolic rates (0.44 and 0.88 m/s walking), two water temperatures (10 and 15°C), and two immersion depths (chest and waist) were used to elicit different rates of Tcore changes. Root mean square deviation (RMSD) and nonparametric Bland-Altman tests were used to test for acceptable model predictions. Using the RMSD criterion, the 3-CTM did not fit the observed data in any trial, whereas the 6-CTM fit the data (RMSD less than standard deviation) in four of eight trials. In general, the 3-CTM predicted a rapid decline in core temperature followed by a plateau. For the 6-CTM, the predicted Tcore appeared relatively tight during the early part of immersion, but was much lower during the latter portions of immersion, accounting for the nonagreement between RMSD and SD values. The 6-CTM was rerun with no adjustment for exercise metabolism, and core temperature and heat loss predictions were tighter. In summary, this study demonstrated that both thermoregulatory models designed for sedentary cold exposure, currently, cannot be extended for use during partial immersion exercise in cold water. Algorithms need to be developed to better predict heat loss during exercise in cold water.

The impact of exercise training on sympathetic activation is not well understood, especially across untrained and trained limbs in athletes. Therefore, in eight sedentary subjects (maximal oxygen consumption = 40 ± 2 ml·kg−1·min−1) and eight competitive cyclists (maximal oxygen consumption= 64 ± 2 ml·kg−1·min−1), we evaluated heart rate, blood pressure, blood flow, vascular conductance, and vascular resistance in the leg and arm during acute sympathetic stimulation [cold pressor test (CPT)]. The CPT was also performed during dynamic leg (knee extensor) or arm (handgrip) exercise at 50% of maximal work rate (WRmax) with measurements in the exercising limb. At rest, the CPT decreased vascular conductance similarly in the leg and arm of sedentary subjects (−33 ± 8% leg, −38 ± 6% arm) and cyclists (−34 ± 4% leg, −31 ± 9% arm), and during exercise CPT-induced vasoconstriction was blunted (i.e., sympatholysis) in both the leg and arm of both groups. However, the magnitude of sympatholysis was significantly different between the arm and leg of the sedentary group (−47 ± 11% arm, −25 ± 8% leg), and it was less in the arm of cyclists (−28 ± 11%) than sedentary controls. Taken together, these data provide evidence that sympathetically mediated vasoconstriction is expressed equally and globally at rest in both sedentary and trained individuals, with a differential pattern of vasoconstriction during acute exercise according to limb and exercise training status.

Older individuals' ability to maintain core temperature during cold stress is impaired; however, the relative importance of individual characteristics that influence this response are unknown. The purpose of this study was to determine the relative influence of individual characteristics on core temperature and tissue insulation (I(t)) during mild cold stress. Forty-two young (23 +/- 1 yr, range 18-30 yr) and 46 older (71 +/- 1 yr, range 65-89 yr) subjects, varying widely in muscularity, adiposity, and body size, underwent a transient cooling protocol during which esophageal temperature (T(es)) was measured continuously and I(t) was calculated using standard equations. Multiple-regression analyses were performed to determine predictors of T(es) and I(t), and standardized regression coefficients were analyzed to determine the relative influence of each predictor. Candidate predictors included age, sex, weight, body surface area, body surface area-to-mass ratio, sum of skinfolds, percent fat, appendicular skeletal muscle mass, and thyroid hormone concentrations (triiodothyronine, thyronine). The sum of skinfolds explained 67% (P0.01) of the T(es) variance in young subjects vs. 2% (P = 0.30) in older subjects. Conversely, appendicular skeletal muscle mass explained a greater portion of the variance in older subjects for both T(es) (older: 28%, P0.01; young: 8%, not significant) and I(t) (older: 46%, P0.01; young: 17%, P0.01). The T(es) residual variance was considerably larger in older subjects (59-72% vs. 14-42% in young subjects), possibly due to varying rates of physiological aging. These results suggest that the relative influence of individual characteristics changes with aging.

Normal brain functioning largely depends on maintaining brain temperature. However, the mechanisms protecting brain against a cooler environment are poorly understood. Reported herein is the first detailed measurement of the brain-temperature profile. It is found to be exponential, defined by a characteristic temperature shielding length, with cooler peripheral areas and a warmer brain core approaching body temperature. Direct cerebral blood flow (CBF) measurements with microspheres show that the characteristic temperature shielding length is inversely proportional to the square root of CBF in excellent agreement with a theoretical model. This “temperature shielding effect” quantifies the means by which CBF prevents “extracranial cold” from penetrating deep brain structures. The effect is crucial for research and clinical applications; the relationship between brain, body, and extracranial temperatures can now be quantitatively predicted.

We examined the influence of 1) prior increase [preheating (PHT)], 2) increase throughout [heating (HT)], and 3) no increase [control (Con)] of body heat content (Hb) on neuromuscular function and manual dexterity of the hands during a 130-min exposure to −20°C (coldEx). Ten volunteers randomly underwent three passive coldEx, incorporating a 10-min moderate-exercise period at the 65th min while wearing a liquid conditioning garment (LCG) and military arctic clothing. In PHT, 50°C water was circulated in the LCG before coldEx until core temperature was increased by 0.5°C. In HT, participants regulated the inlet LCG water temperature throughout coldEx to subjective comfort, while the LCG was not operating in Con. Thermal comfort, rectal temperature, mean skin temperature, mean finger temperature (T̄fing), change in Hb (ΔHb), rate of body heat storage, Purdue pegboard test, finger tapping, handgrip, maximum voluntary contraction, and evoked twitch force of the first dorsal interosseus muscle were recorded. Results demonstrated that, unlike in HT and PHT, thermal comfort, rectal temperature, mean skin temperature, twitch force, maximum voluntary contraction, and finger tapping declined significantly in Con. In contrast, T̄fing and Purdue pegboard test remained constant only in HT. Generalized estimating equations demonstrated that ΔHb and T̄fing were associated over time with hand function, whereas no significant association was detected for rate of body heat storage. It is concluded that increasing Hb not only throughout but also before a coldEx is effective in maintaining hand function. In addition, we found that the best indicator of hand function is ΔHb followed by T̄fing.

The ventilatory responses to immersion and changes in temperature are reviewed. A fall in skin temperature elicits a powerful cardiorespiratory response, termed “cold shock,” comprising an initial gasp, hypertension, and hyperventilation despite a profound hypocapnia. The physiology and neural pathways of this are examined with data from original studies. The respiratory responses to skin cooling override both conscious and other autonomic respiratory controls and may act as a precursor to drowning. There is emerging evidence that the combination of the reestablishment of respiratory rhythm following apnea, hypoxemia, and coincident sympathetic nervous and cyclic vagal stimulation appears to be an arrhythmogenic trigger. The potential clinical implications of this during wakefulness and sleep are discussed in relation to sudden death during immersion, underwater birth, and sleep apnea. A drop in deep body temperature leads to a slowing of respiration, which is more profound than the reduced metabolic demand seen with hypothermia, leading to hypercapnia and hypoxia. The control of respiration is abnormal during hypothermia, and correction of the hypoxia by inhalation of oxygen may lead to a further depression of ventilation and even respiratory arrest. The immediate care of patients with hypothermia needs to take these factors into account to maximize the chances of a favorable outcome for the rescued casualty.

This review focuses on the neural and local mechanisms that have been demonstrated to effect cutaneous vasodilation and vasoconstriction in response to heat and cold stress in vivo in humans. First, our present understanding of the mechanisms by which sympathetic cholinergic nerves mediate cutaneous active vasodilation during reflex responses to whole body heating is discussed. These mechanisms include roles for cotransmission as well as nitric oxide (NO). Next, the mechanisms by which sympathetic noradrenergic nerves mediate cutaneous active vasoconstriction during whole body cooling are reviewed, including cotransmission by neuropeptide Y (NPY) acting through NPY Y1 receptors. Subsequently, current concepts for the mechanisms that effect local cutaneous vascular responses to direct skin warming are examined. These mechanisms include the roles of temperature-sensitive afferent neurons as well as NO in causing vasodilation during local heating of skin. This section is followed by a review of the mechanisms that cause local cutaneous vasoconstriction in response to direct cooling of the skin, including the dependence of these responses on intact sensory and sympathetic, noradrenergic innervation as well as roles for nonneural mechanisms. Finally, unresolved issues that warrant further research on mechanisms that control cutaneous vascular responses to heating and cooling are discussed.

This study compared the effects of hypohydration (HYP) on endurance exercise performance in temperate and cold air environments. On four occasions, six men and two women (age = 24 ± 6 yr, height = 170 ± 6 cm, weight = 72.9 ± 11.1 kg, peak O2 consumption = 48 ± 9 ml·kg−1·min−1) were exposed to 3 h of passive heat stress (45 °C) in the early morning with [euhydration (EUH)] or without (HYP; 3% body mass) fluid replacement. Later in the day, subjects sat in a cold (2 °C) or temperate (20 °C) environment with minimal clothing for 1 h before performing 30 min of cycle ergometry at 50% peak O2 consumption followed immediately by a 30-min performance time trial. Rectal and mean skin temperatures, heart rate, and ratings of percieved exertion measurements were made at regular intervals. Performance was assessed by the total amount of work (kJ) completed in the 30-min time trial. Skin temperature was significantly lower in the cold compared with the temperate trial, but there was no independent effect of hydration. Rectal temperature in both HYP trials was higher than EUH after 60 min of exercise, but the difference was only significant within the temperate trials ( P < 0.05). Heart rate was significantly higher at 30 min within the temperate trial (HYP > EUH) and at 60 min within the cold trial (HYP > EUH) ( P < 0.05). Ratings of percieved exertion increased over time with no differences among trials. Total work performed during the 30-min time trial was not influenced by environment but was less ( P < 0.05) for HYP than EUH in the temperate trials. The corresponding change in performance (EUH − HYP) was greater for temperate (−8%) than for cold (−3%) ( P < 0.05). These data demonstrate that 1) HYP impairs endurance exercise performance in temperate but not cold air but 2) cold stress per se does not.

Previous studies have documented that repetitive exposure to intermittent hypoxia, such as that encountered in preparation to high-altitude ascent, influences breathing. However, the impact of intermittent hypoxia on airway smooth muscle has not been explored. Ascents to high altitude, in addition to hypoxia, expose individuals to cold air. The objective of the present study is to examine the effect of chronic intermittent hypobaric hypoxia (CIH) and CIH combined with cold exposure (CIHC) on tracheal smooth muscle responses to various contractile and relaxant agonists. Experiments were performed on tracheal rings harvested from adult guinea pigs exposed either to CIH or CIHC [14 days (6 h/day) at barometric pressure of 350 mmHg with and without cold exposure of 5°C] or to room air (normoxia). CIH and CIHC attenuated maximum contractile responses to ACh compared with normoxia. The maximum contractile response to histamine decreased with CIH, whereas CIHC restored the response back to normoxia. Both CIH and CIHC attenuated maximum contractile responses to 5-HT. Altered contractile responses after CIH and CIHC were independent of epithelium. Isoproterenol-induced relaxation was not altered by CIH, whereas it was enhanced after CIHC, and these responses were independent of the epithelium. The data demonstrate that intermittent exposure to hypoxia profoundly influences contractile response of tracheal smooth muscle, and cold exposure can further modulate the response, implying the importance of cold at high altitude.

Hypohydration occurs during cold-air exposure (CAE) through combined effects of reduced fluid intake and increased fluid losses. Because hypohydration is associated with reduced physical performance, strategies for maintaining hydration during CAE are important. Glycerol ingestion (GI) can induce hyperhydration in hot and temperate environments, resulting in greater fluid retention compared with water (WI) alone, but it is not effective during cold-water immersion. Water immersion induces a greater natriuresis and diuresis than cold exposure; therefore, whether GI might be effective for hyperhydration during CAE remains unknown. This study examined physiological responses, i.e., thermoregulatory, cardiovascular, renal, vascular fluid, and fluid-regulating hormonal responses, to GI in seven men during 4 h CAE (15°C, 30% relative humidity). Subjects completed three separate, double-blind, and counterbalanced trials including WI (37 ml water/l total body water), GI (37 ml water/l total body water plus 1.5 g glycerol/l total body water), and no fluid. Fluids were ingested 30 min before CAE. Thermoregulatory responses to cold were similar during each trial. Urine flow rates were higher ( P = 0.0001) with WI (peak 11.8 ml/min, SD 1.9) than GI (5.0 ml/min, SD 1.8), and fluid retention was greater ( P = 0.0001) with GI (34%, SD 7) than WI (18%, SD 5) at the end of CAE. Differences in urine flow rate and fluid retention were the result of a greater free water clearance with WI. These data indicate glycerol can be an effective hyperhydrating agent during CAE.

Cold-induced vasodilation (CIVD) is a cyclic oscillation in blood flow that occurs in the extremities on cold exposure and that is likely associated with reduced risk of cold injury (e.g., frostbite) as well as improved manual dexterity and less pain while working in the cold. The CIVD response varies between individuals, but the within-subject reproducibility has not been adequately described. The purpose of this study was to quantify the within-subject variability in the CIVD response under standardized conditions. Twenty-one volunteers resting in a controlled environment (27°C) immersed the middle finger in warm water (42°C) for 15 min to standardize initial finger temperature and then in cold water (4°C; CWI) for 30 min, on five separate occasions. Skin temperature (Tf) and blood flow (laser-Doppler; expressed as percent change from warm-water peak) responses that describe CIVD were identified, including initial nadir reached during CWI, onset time of CIVD, initial apex during CIVD, time of that apex, and overall mean during CWI. Within-subject coefficient of variation for Tfacross the five tests for the nail bed and pad, respectively, were as follows: nadir, 9 and 21%; onset, 18 and 19%; apex, 12 and 17%; apex time, 23 and 24%; mean 10 and 15%. For blood flow, these values were as follows: nadir 52 and 64%; onset, 6 and 5%; apex, 33 and 31%; apex time 9 and 8%; and mean 43 and 34%. Greater variability was found in the temperature response of the finger pad than the nail bed, but for blood flow the variability was similar between locations. Variability in onset and apex time between sites was similar for both temperature and blood flow responses. The reproducibility of the time course of CIVD suggests this methodology may be of value for further studies examining the mechanism of the response.

Temperature regulation during exercise in the cold was examined in 13 adolescent female individuals, aged 13-18 yr. Six girls with established menstrual cycles comprised the eumenorrheic menarcheal (EM) group, and seven nonmenstruating girls comprised the premenarcheal (PM) group. During the first visit, maximal oxygen consumption (V̇o2 max), height, weight, and percent body fat were measured. The second visit included a determination of metabolic rate in thermoneutrality (21°C), consisting of a 10-min rest period and 20 min of cycling (30% of V̇o2 max), and a cold test (5°C, 40% humidity, 2 max). Subjects in the EM group were tested twice in the chamber: once during the follicular and once during the luteal phase. Heat production per kilogram in thermoneutrality and in the cold was significantly ( P < 0.05) higher in the PM compared with the EM girls. However, the PM girls had a significantly ( P < 0.05) lower core temperature in the cold than the EM group. PM girls also had a significantly higher body surface area-to-mass ratio compared with the EM girls. Although percent body fat between groups was not significantly different, within the PM group percent body fat explained 79% ( P < 0.01) of the variance in the decrease of core temperature. There were no menstrual phase-related differences in temperature regulation in either the thermoneutral or cold environment. In conclusion, menstrual phase does not influence temperature regulation in female individuals during adolescence. EM girls had lower metabolic heat production but maintained their core temperature more effectively in the cold than did the PM girls. This thermoregulatory difference between PM and EM girls is mainly a function of geometric differences with maturation-related peripheral vasoconstrictive differences maybe limiting the effectiveness of the mechanism of increased heat storage in younger female individuals.

The effects of long-term cold exposure on muscle and liver mitochondrial oxygen consumption in hypothyroid and normal rats were examined. Thyroid ablation was performed after 8-wk acclimation to 4°C. Hypothyroid and normal controls remained in the cold for an additional 8 wk. At the end of 16-wk cold exposure, all hypothyroid rats were alive and normothermic and had normal body weight. At ambient temperature (24°C), thyroid ablation induced a 65% fall in muscle mitochondrial oxygen consumption, which was reversed by thyroxine but not by norepinephrine administration. After cold acclimation was reached, suppression of thyroid function reduced muscle mitochondrial respiration by 30%, but the hypothyroid values remained about threefold higher than those in hypothyroid muscle in the warm. Blockade of β- and α1-adrenergic receptors in both hypothyroid and normal rats produced hypothermia in vivo and a fall in muscle, liver, and brown adipose tissue mitochondria respiration in vitro. In normal rats, cold acclimation enhanced muscle respiration by 35%, in liver 18%, and in brown adipose tissue 450% over values in the warm. The results demonstrate that thyroid hormones, in the presence of norepinephrine, are major determinants of thermogenic activity in muscle and liver of cold-acclimated rats. After thyroid ablation, cold-induced nonshivering thermogenesis replaced 3,5,3′-triiodothyronine-induced thermogenesis, and normal body temperature was maintained.

This study evaluated blood pressure and heart rate responses to exercise and nonexercise tasks as indexes of autonomic function in subjects with and without Down syndrome (DS). Twenty-four subjects (12 with and 12 without DS) completed maximal treadmill exercise, isometric handgrip (30% of maximum), and cold pressor tests, with heart rate and blood pressure measurements. Maximal heart rate and heart rate and blood pressure responses to the isometric handgrip and cold pressor tests were reduced in subjects with DS ( P < 0.05). Both early (first 30 s) and late (last 30 s) responses were reduced. Obesity did not appear to influence the results, as both obese and normal-weight subjects with DS exhibited similar responses, and controlling for body mass index did not alter the results between controls and subjects with DS. Individuals with DS, without congenital heart disease, exhibit reduced heart rate and blood pressure responses to isometric handgrip exercise and cold pressor testing, consistent with autonomic dysfunction. Autonomic dysfunction may partially explain chronotropic incompetence observed during maximal treadmill exercise in individuals with DS.

Obstructive sleep apnea (OSA) patients exhibit altered sympathetic outflow, which may reveal mechanisms underlying the syndrome. We used functional MRI (fMRI) in 16 control and 10 OSA subjects who were free of cardiovascular or mood-altering drugs to examine neural responses to a forehead cold pressor challenge, which elicits respiratory slowing, bradycardia, and enhanced sympathetic outflow. The magnitude of cold-induced bradycardia was smaller, and respiratory slowing showed greater intersubject variability and reached a nadir later in OSA patients. Both groups showed similar signal changes to cold stimulation in multiple brain sites. However, signal increases emerged in OSA over controls in anterior and posterior cingulate and cerebellar and frontal cortex, whereas signals markedly declined in the ventral thalamus, hippocampus, and insula rather than rising as in controls. Anomalous responses often paralleled changes in breathing and heart rate. Medullary, midbrain areas and lentiform and cerebellar dentate nuclei also showed lower signals in OSA cases. Cold pressor physiological responses are modified in OSA and may result from both diminished and exaggerated responses in multiple brain structures.

This study was conducted to determine whether hypohydration (Hy) alters blood flow, skin temperature, or cold-induced vasodilation (CIVD) during peripheral cooling. Fourteen subjects sat in a thermoneutral environment (27°C) during 15-min warm-water (42°C) and 30-min cold-water (4°C) finger immersion (FI) while euhydrated (Eu) and, again, during Hy. Hy (−4% body weight) was induced before FI by exercise-heat exposure (38°C, 30% relative humidity) with no fluid replacement, whereas during Eu, fluid intake maintained body weight. Finger pad blood flow [as measured by laser-Doppler flux (LDF)] and nail bed (Tnb), pad (Tpad), and core (Tc) temperatures were measured. LDF decreased similarly during Eu and Hy (32 ± 10 and 33 ± 13% of peak during warm-water immersion). Mean Tnb and Tpad were similar between Eu (7.1 ± 1.0 and 11.5 ± 1.6°C) and Hy (7.4 ± 1.3 and 12.6 ± 2.1°C). CIVD parameters (e.g., nadir, onset time, apex) were similar between trials, except Tpad nadir was higher during Hy (10.4 ± 3.8°C) than during Eu (7.9 ± 1.6°C), which was attributed to higher Tc in six subjects during Hy (37.5 ± 0.2°C), compared with during Eu (37.1 ± 0.1°C). The results of this study provide no evidence that Hy alters finger blood flow, skin temperature, or CIVD during peripheral cooling.

This study determined the role of body temperature during exercise on cytochrome- c oxidase (CytOx) activity, a marker of mitochondrial content, and mitochondrial heat shock protein 70 (mtHSP70), which is required for import of nuclear-coded preproteins. Male, 10-wk-old, Sprague-Dawley rats exercised identically for 9 wk in ambient temperatures of 23°C ( n = 10), 8°C with wetted fur ( n = 8), and 4°C with wetted fur and fan ( n = 7). These conditions maintained exercising core temperature (Tc) at 40.4, 39.2, or 38.0°C (resting temperature), respectively. During weeks 3–9, exercisers ran 5 days/wk up a 6% grade at 20 m/min for 60 min. Animals were housed at 23°C. Gastrocnemius CytOx activity in Tc=38.0°C (83.5 ± 5.5 μatoms O · min−1· g wet wt−1) was greater than all other groups ( P< 0.05), exceeding sedentary ( n = 7) by 73.2%. Tcof 40.4 and 39.2°C also were higher than sedentary by 22.4 and 37.4%, respectively ( P < 0.05). Quantification of CytOx content verified that the increased activity was due to an increase in protein content. In extensor digitorum longus, a nonactive muscle, CytOx was not elevated in Tc= 38.0°C. mtHSP70 was significantly elevated in gastrocnemius of Tc= 38.0°C compared with sedentary ( P < 0.05) but was not elevated in extensor digitorum longus ( P > 0.05). The data indicate that decreasing exercise Tcmay enhance mitochondrial biogenesis and that mtHSP70 expression is not dependent on temperature.

The relative roles of circulatory glucose, muscle glycogen, and lipids in shivering thermogenesis are unclear. Using a combination of indirect calorimetry and stable isotope methodology ([U-13C]glucose ingestion), we have quantified the oxidation rates of these substrates in men acutely exposed to cold for 2 h (liquid conditioned suit perfused with 10°C water). Cold exposure stimulated heat production by 2.6-fold and increased the oxidation of plasma glucose from 39.4 ± 2.4 to 93.9 ± 5.5 mg/min (+138%), of muscle glycogen from 126.6 ± 7.8 to 264.2 ± 36.9 mg glucosyl units/min (+109%), and of lipids from 46.9 ± 3.2 to 176.5 ± 17.3 mg/min (+376%). Despite the observed increase in plasma glucose oxidation, this fuel only supplied 10% of the energy for heat generation. The major source of carbohydrate was muscle glycogen (75% of all glucose oxidized), and lipids produced as much heat as all other fuels combined. During prolonged, low-intensity shivering, we conclude that total heat production is unequally shared among lipids (50%), muscle glycogen (30%), plasma glucose (10%), and proteins (10%). Therefore, future research should focus on lipids and muscle glycogen that provide most of the energy for heat production.