Metabolic effects of exposure to hypoxia plus cold at rest and during exercise in humans KEITH
A. ROBINSON
Department
ROBINSON,
KEITH
A.,
AND
EMILY
M. HAYMES
of Movement Science, Florida State University, Tallahassee, Florida 32306
AND
EMILY
M.
HAYMES.
Metabolic
effects of exposure to hypoxiaplus cold at rest and during exercise in humans. J. Appl. Physiol. 68(2): 720-725, 1990.-To deter-
mine effects on metabolic responses,subjectswere exposedto four environmental conditions for 90 min at rest followed by 30 min of exercise:breathing room air with an ambient temperature of 25°C (NN); breathing room air with an ambient temperature of 8°C (NC); hypoxia (induced by breathing 12% O2in N2) with a neutral temperature (HN); and hypoxia in the cold (HC). Hypoxia increasedheart rate (HR), systolic blood pressure(SBP), pulmonary ventilation (VE), respiratory exchangeratio (R), blood lactate, and perceived exertion during exercisewhile depressingrectal temperature (T,,) and O2uptake (VO,). Cold e?posureelevated SBP, diastolic blood pressure (DBP), VE, VOW,blood glucose,and blood glycerol but decreasedHR, T,,, and R. Shivering and DBP were higher and T,, waslower in HC comparedwith NC. HR, SBP, \17E, R, and lactate tended to be higher in HC comparedwith NC, whereas VO, and blood glycerol tended to be depressed.These results suggestthat cold exposure during hypoxia results in an increasedrelianceon shivering for thermogenesisat rest whereas, during exercise,heat lossis accelerated. thermogenesis THE METABOLIC EFFECTS of exposure to either cold temperatures or hypoxia have been previously reported. Exposure to cold in resting human subjects results in a substantial increase in 02 uptake (VOW) that is supported primarily by the mobilization and utilization of free fatty acids (FFA) from adipose tissue triglyceride stores (26, 30). However, the muscular activity of shivering appears to be dependent on the catabolism of skeletal muscle glycogen stores as an energy source (24). The total energy cost of submaximal work is greater in the cold than at neutral temperatures (2); Vo2 is increased for a given submaximal work load in the cold, and the maximum O2 uptake (vo2 max)may be reduced when both the skin and core temperatures are depressed (5). Submaximal exercise in the cold appears to be more reliant on the catabolism of FFA as an energy source than exercise of the same intensity in a neutral environment (21). In con-
the anaerobic catabolism of blood glucose and intramuscular glycogen as energy substrates for muscular work with a concomitant increase in lactic acid formation by working muscle and its subsequent appearance in the circulation. In dogs, acute cold exposure increases the metabolic rate primarily via an increase in FFA catabolism (27, 29). However, previous studies have established that increases in Vo2 associated with exposure to cold are reduced by simultaneous hypoxia in animals (4, 6). Some early investigations of this phenomenon in human beings failed to confirm these results, but more recent and appropriately controlled studies have demonstrated that thermogenesis is blunted by hypoxia in human subjects. Blatteis and Lutherer (7) showed that, because of increased shivering despite decreased Vo2 during exposure to cold at high altitude, the primary component affected was nonshivering thermogenesis. Because the primary metabolic support for nonshivering thermogenesis appears to be stored fat, fat metabolism may be depressed in hypoxic cold; however, patterns of substrate utilization in humans exposed to these conditions have apparently not been reported. Documentation of these patterns and other physiological responses is of potential importance for understanding the homeostatic arbitration of environmental demands that may require complementary or conflicting adjustments. Furthermore, the additional ergogenic demand imposed by exercise may reveal responses that are insignificant or blunted during exposure at rest. The present study was therefore undertaken to examine the effects of exposure to hypoxia, cold, and a combination of the two stressors on physiological responses both at rest and during exercise. METHODS
Subjects. Seven normal, healthy men volunteered to participate in this study. Informed consent was obtained before the initiation of any experimentation and the experimental protocol was explained to the subjects. Determination of body composition (23), voluntary . trast, exposure to high altitude, or the breathing of gas vo 2 max (l4), and work load on the cycle ergometer at mixtures low in 02 content, results in resting and sub- 50% HR reserve was performed before environmental maximal exercise Tjo2 values slightly lower than under exposures. This exercise intensity was selected to enable normoxic conditions (lo), although pulmonary ventilacompletion of 30 min of work while breathing 12% 02 in tion (VE) and heart rate (HR) are augmented. Increases N2, and it was determined as: 0.5 X (age-predicted maxin the blood conceptration of lactic acid are observed, as imum HR - resting HR). Questionnaires relevant to diet well as reductio s in v02 max(12, 17, 18, 20). Such data and exercise habits were given to the subjects after suggest that h Yifoxia mandates an increased reliance on completion of the experiments. No major changes in diet 720
0161-7567/90
$1.50 Copyright
0 1990 the American
Physiological
Society
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (128.111.121.042) on August 12, 2018. Copyright © 1990 American Physiological Society. All rights reserved.
METABOLISM
IN HYPOXIA
or exercise habits were reported by any subject for the duration of the time during which the experiments were conducted; therefore, it was assumed that body composition and physical fitness remained constant. Experimental protocol. Each subject was exposed to four different environmental conditions: breathing air (normoxia) with an ambient temperature of 25°C (normoxia-neutral, NN); normoxia with an ambient temperature of 8°C (normoxia-cold, NC); hypoxia induced by breathing 12% O2 in Nz (Air Products, Inc.) at a neutral temperature (hypoxia-neutral, HN); and hypoxia in the cold (hypoxia-cold, HC). Only one exposure per subject per week was performed, the order of exposures was randomly assigned, and the subjects were blinded to the order of exposures. Subjects wore only shorts, socks, and shoes for all exposures; the whole body surface but not the airway (see below) was thus exposed to the neutral or cold temperature. Subjects reported to the laboratory at 7:30 A.M. after an overnight fast during which time no alcohol, caffeine, or nicotine was consumed and no strenuous exercise was performed. A rectal thermistor was then introduced to a depth of 10 cm and the subjects rested quietly seated in a chair for 30 min, at which time the base-line values for HR, systolic (SBP) and diastolic (DBP) blood pressure, rectal temperature (T,,), VE, and Tjo2 were obtained. A blood sample was drawn by needle puncture of the median or cephalic vein in the antecubital fossa for analysis of whole blood glucose, lactate, and glycerol concentrations. The subjects then entered the environmental chamber (Heinecke) for 90 min of resting exposure followed by 30 min of exercise. Although a steady state of thermogenesis as reflected by Vo2 was achieved early in the 90-min resting exposure, T,, continued to decline; however, the T,, declined at a comparable rate in the neutral environment as well, so that one may reasonably assume a thermal steady-state adjustment. Other investigators have used cold exposures of similar duration (7, 11, 21). Repeat blood samples were taken at 45 and 90 min of resting exposure, and 5 min postexercise (to obtain peak lactate values). All other measurements were performed every 15 min throughout the entire exposure. Shivering
721
PLUS COLD
was measured by electromyography via skin surface electrodes on the sternocleidomastoid muscle for 1 min every 5 min during cold exposures. The input was integrated on a Grass 7B physiograph to yield a trace with only unidirectional deflection that was subsequently traced with a line of best fit; the area that appeared between the curve thus described and the base line was summed, and an average value of shivering in millivolts per minute was obtained for each subject exposure. Subjects inspired either air or the hypoxic gas mixture via a J valve and hoses connected to a 600-liter Tissot spirometer outside the chamber. Humidity of the inspired gas was therefore constant across the different conditions. Expired air samples were collected for 1 min in a meteorological balloon and analyzed for O2 (S-3A, Applied Electrochemistry) and COa (CD3A, Ametec) content, as well as gas volume (5-M-210, American Meter Co.). Respiratory exchange ratio (R) was calculated as: VCO&O~. Vo2 was calculated according to the following equation . vo 2= ~TPD X { [ 1.0 - (FEo, + FE,,,)] x
FIo,/(FIN,
-
FEO,)
j
Blood lactate and glycerol (an index of overall FFA turnover, Ref. 33) were assayed by enzymatic procedures (Refs. 31 and 16, respectively) and blood glucose colorometrically using o-toluidine as a reagent (22). A series of blood lactate measurements was validated against a nonenzymatic method and found to vary ~2%. All blood chemistry analyses were performed in duplicate on a Gilford spectrophotometer and the results averaged to obtain the final values. Perception of whole body exertion during exercise was assessed by using the Borg scale and prearranged hand signals at 15 and 30 min of exercise. Statistical analysis. A 2 x 2 x 8 experimental design was used in which each subject served as his own control. The treatment factors were 1) O2 content of the inspired gas mixture (normoxia or hypoxia), 2) ambient temperature (neutral or cold), and 3) time of exposure. A threeway analysis of variance with repeated measures was used to test the null hypothesis. In the event of a signif-
EXERCISE I
160 1
I
0 N-N l N-C
* H-N A H-C I
t
60 1 40 !
FIG. 1. Mean heart rate values at 15min intervals throughout rest and exercise for 4 different environmental conditions. P < 0.001 for hypoxic vs. normoxic conditions throughout rest and exercise; P < 0.05 for cold vs. neutral conditions during exercise only.
I 0
I 15
I 30
I 45 TIME,
I 1 60 75 MINUTES
I 90
I 105
I 120
c
I
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (128.111.121.042) on August 12, 2018. Copyright © 1990 American Physiological Society. All rights reserved.
722
METABOLISM
IN
HYPOXIA
Time
NC 84t8 HC 93k7 P
of Exposure
30 min
45 min
60 min
869
89k12 92t5
89t7
89t3
89&6
85t5
79t9
8926
88t9
8726
8326
8125
NS
NS
NS
90t5
A. ROBINSON
Department
ROBINSON,
KEITH
A.,
AND
EMILY
M. HAYMES
of Movement Science, Florida State University, Tallahassee, Florida 32306
AND
EMILY
M.
HAYMES.
Metabolic
effects of exposure to hypoxiaplus cold at rest and during exercise in humans. J. Appl. Physiol. 68(2): 720-725, 1990.-To deter-
mine effects on metabolic responses,subjectswere exposedto four environmental conditions for 90 min at rest followed by 30 min of exercise:breathing room air with an ambient temperature of 25°C (NN); breathing room air with an ambient temperature of 8°C (NC); hypoxia (induced by breathing 12% O2in N2) with a neutral temperature (HN); and hypoxia in the cold (HC). Hypoxia increasedheart rate (HR), systolic blood pressure(SBP), pulmonary ventilation (VE), respiratory exchangeratio (R), blood lactate, and perceived exertion during exercisewhile depressingrectal temperature (T,,) and O2uptake (VO,). Cold e?posureelevated SBP, diastolic blood pressure (DBP), VE, VOW,blood glucose,and blood glycerol but decreasedHR, T,,, and R. Shivering and DBP were higher and T,, waslower in HC comparedwith NC. HR, SBP, \17E, R, and lactate tended to be higher in HC comparedwith NC, whereas VO, and blood glycerol tended to be depressed.These results suggestthat cold exposure during hypoxia results in an increasedrelianceon shivering for thermogenesisat rest whereas, during exercise,heat lossis accelerated. thermogenesis THE METABOLIC EFFECTS of exposure to either cold temperatures or hypoxia have been previously reported. Exposure to cold in resting human subjects results in a substantial increase in 02 uptake (VOW) that is supported primarily by the mobilization and utilization of free fatty acids (FFA) from adipose tissue triglyceride stores (26, 30). However, the muscular activity of shivering appears to be dependent on the catabolism of skeletal muscle glycogen stores as an energy source (24). The total energy cost of submaximal work is greater in the cold than at neutral temperatures (2); Vo2 is increased for a given submaximal work load in the cold, and the maximum O2 uptake (vo2 max)may be reduced when both the skin and core temperatures are depressed (5). Submaximal exercise in the cold appears to be more reliant on the catabolism of FFA as an energy source than exercise of the same intensity in a neutral environment (21). In con-
the anaerobic catabolism of blood glucose and intramuscular glycogen as energy substrates for muscular work with a concomitant increase in lactic acid formation by working muscle and its subsequent appearance in the circulation. In dogs, acute cold exposure increases the metabolic rate primarily via an increase in FFA catabolism (27, 29). However, previous studies have established that increases in Vo2 associated with exposure to cold are reduced by simultaneous hypoxia in animals (4, 6). Some early investigations of this phenomenon in human beings failed to confirm these results, but more recent and appropriately controlled studies have demonstrated that thermogenesis is blunted by hypoxia in human subjects. Blatteis and Lutherer (7) showed that, because of increased shivering despite decreased Vo2 during exposure to cold at high altitude, the primary component affected was nonshivering thermogenesis. Because the primary metabolic support for nonshivering thermogenesis appears to be stored fat, fat metabolism may be depressed in hypoxic cold; however, patterns of substrate utilization in humans exposed to these conditions have apparently not been reported. Documentation of these patterns and other physiological responses is of potential importance for understanding the homeostatic arbitration of environmental demands that may require complementary or conflicting adjustments. Furthermore, the additional ergogenic demand imposed by exercise may reveal responses that are insignificant or blunted during exposure at rest. The present study was therefore undertaken to examine the effects of exposure to hypoxia, cold, and a combination of the two stressors on physiological responses both at rest and during exercise. METHODS
Subjects. Seven normal, healthy men volunteered to participate in this study. Informed consent was obtained before the initiation of any experimentation and the experimental protocol was explained to the subjects. Determination of body composition (23), voluntary . trast, exposure to high altitude, or the breathing of gas vo 2 max (l4), and work load on the cycle ergometer at mixtures low in 02 content, results in resting and sub- 50% HR reserve was performed before environmental maximal exercise Tjo2 values slightly lower than under exposures. This exercise intensity was selected to enable normoxic conditions (lo), although pulmonary ventilacompletion of 30 min of work while breathing 12% 02 in tion (VE) and heart rate (HR) are augmented. Increases N2, and it was determined as: 0.5 X (age-predicted maxin the blood conceptration of lactic acid are observed, as imum HR - resting HR). Questionnaires relevant to diet well as reductio s in v02 max(12, 17, 18, 20). Such data and exercise habits were given to the subjects after suggest that h Yifoxia mandates an increased reliance on completion of the experiments. No major changes in diet 720
0161-7567/90
$1.50 Copyright
0 1990 the American
Physiological
Society
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (128.111.121.042) on August 12, 2018. Copyright © 1990 American Physiological Society. All rights reserved.
METABOLISM
IN HYPOXIA
or exercise habits were reported by any subject for the duration of the time during which the experiments were conducted; therefore, it was assumed that body composition and physical fitness remained constant. Experimental protocol. Each subject was exposed to four different environmental conditions: breathing air (normoxia) with an ambient temperature of 25°C (normoxia-neutral, NN); normoxia with an ambient temperature of 8°C (normoxia-cold, NC); hypoxia induced by breathing 12% O2 in Nz (Air Products, Inc.) at a neutral temperature (hypoxia-neutral, HN); and hypoxia in the cold (hypoxia-cold, HC). Only one exposure per subject per week was performed, the order of exposures was randomly assigned, and the subjects were blinded to the order of exposures. Subjects wore only shorts, socks, and shoes for all exposures; the whole body surface but not the airway (see below) was thus exposed to the neutral or cold temperature. Subjects reported to the laboratory at 7:30 A.M. after an overnight fast during which time no alcohol, caffeine, or nicotine was consumed and no strenuous exercise was performed. A rectal thermistor was then introduced to a depth of 10 cm and the subjects rested quietly seated in a chair for 30 min, at which time the base-line values for HR, systolic (SBP) and diastolic (DBP) blood pressure, rectal temperature (T,,), VE, and Tjo2 were obtained. A blood sample was drawn by needle puncture of the median or cephalic vein in the antecubital fossa for analysis of whole blood glucose, lactate, and glycerol concentrations. The subjects then entered the environmental chamber (Heinecke) for 90 min of resting exposure followed by 30 min of exercise. Although a steady state of thermogenesis as reflected by Vo2 was achieved early in the 90-min resting exposure, T,, continued to decline; however, the T,, declined at a comparable rate in the neutral environment as well, so that one may reasonably assume a thermal steady-state adjustment. Other investigators have used cold exposures of similar duration (7, 11, 21). Repeat blood samples were taken at 45 and 90 min of resting exposure, and 5 min postexercise (to obtain peak lactate values). All other measurements were performed every 15 min throughout the entire exposure. Shivering
721
PLUS COLD
was measured by electromyography via skin surface electrodes on the sternocleidomastoid muscle for 1 min every 5 min during cold exposures. The input was integrated on a Grass 7B physiograph to yield a trace with only unidirectional deflection that was subsequently traced with a line of best fit; the area that appeared between the curve thus described and the base line was summed, and an average value of shivering in millivolts per minute was obtained for each subject exposure. Subjects inspired either air or the hypoxic gas mixture via a J valve and hoses connected to a 600-liter Tissot spirometer outside the chamber. Humidity of the inspired gas was therefore constant across the different conditions. Expired air samples were collected for 1 min in a meteorological balloon and analyzed for O2 (S-3A, Applied Electrochemistry) and COa (CD3A, Ametec) content, as well as gas volume (5-M-210, American Meter Co.). Respiratory exchange ratio (R) was calculated as: VCO&O~. Vo2 was calculated according to the following equation . vo 2= ~TPD X { [ 1.0 - (FEo, + FE,,,)] x
FIo,/(FIN,
-
FEO,)
j
Blood lactate and glycerol (an index of overall FFA turnover, Ref. 33) were assayed by enzymatic procedures (Refs. 31 and 16, respectively) and blood glucose colorometrically using o-toluidine as a reagent (22). A series of blood lactate measurements was validated against a nonenzymatic method and found to vary ~2%. All blood chemistry analyses were performed in duplicate on a Gilford spectrophotometer and the results averaged to obtain the final values. Perception of whole body exertion during exercise was assessed by using the Borg scale and prearranged hand signals at 15 and 30 min of exercise. Statistical analysis. A 2 x 2 x 8 experimental design was used in which each subject served as his own control. The treatment factors were 1) O2 content of the inspired gas mixture (normoxia or hypoxia), 2) ambient temperature (neutral or cold), and 3) time of exposure. A threeway analysis of variance with repeated measures was used to test the null hypothesis. In the event of a signif-
EXERCISE I
160 1
I
0 N-N l N-C
* H-N A H-C I
t
60 1 40 !
FIG. 1. Mean heart rate values at 15min intervals throughout rest and exercise for 4 different environmental conditions. P < 0.001 for hypoxic vs. normoxic conditions throughout rest and exercise; P < 0.05 for cold vs. neutral conditions during exercise only.
I 0
I 15
I 30
I 45 TIME,
I 1 60 75 MINUTES
I 90
I 105
I 120
c
I
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (128.111.121.042) on August 12, 2018. Copyright © 1990 American Physiological Society. All rights reserved.
722
METABOLISM
IN
HYPOXIA
Time
NC 84t8 HC 93k7 P
of Exposure
30 min
45 min
60 min
869
89k12 92t5
89t7
89t3
89&6
85t5
79t9
8926
88t9
8726
8326
8125
NS
NS
NS
90t5
