IN
DEGREE PROJECT MEDICAL ENGINEERING, SECOND CYCLE, 30 CREDITS
,
STOCKHOLM SWEDEN 2020
Thermo-effector responses to a 5-
day high-intensity cold-acclimation
procedure
Termoeffektorsvar på en 5-dagars högintensiv
köldanpassningsprocedur
FREDERICK WILKINS
KTH ROYAL INSTITUTE OF TECHNOLOGY
Thermo-effector responses to
a 5-day high-intensity
cold-acclimation procedure
FREDERICK WILKINS
Master in Medical Engineering Date: June 21, 2020
Supervisor: Assist. Prof. Michail Keramidas, PhD Reviewer: Prof. Ola Eiken, MD, PhD
Examiner: Assoc. Prof. Matilda Larsson, PhD
School of Engineering Sciences in Chemistry, Biotechnology and Health
iii
Abstract
iv
Acknowledgements
The present study was supported by a grant of the Swedish Armed Forces (Grant no.9220918). The participation and effort of all subjects is greatfully acknowledged.
v
Sammanfattning
vi
Abbreviations
AD Body surface area BAT Brown adipose tissue
BCW Body cold water immersion phase BL Baseline phase
BMR Basal metabolic rate
CIT Cold-induced thermogenesis CSR Cold shock response
°C Degrees Celsius
DAP Diastolic arterial pressure HR Heart rate
kg kilogram
KTH Kungliga Tekniska högskolan L Litre
M Metabolic heat production MAP Mean arterial pressure
min Minute mm Millimetre mmHG Millimetre mercury n Number of subjects NST Non-shivering thermogenesis P Probability value
Post Moderate cold (post acclimation) trial Pre Moderate cold (pre acclimation) trial RER Respiratory exchange ratio
RF Respiration frequency SAP Systolic arterial pressure
SD Standard deviation Tb Body temperature
Trec Rectal temperature
∆Trec Changes in rectal temperature Tsk Skin temperature
Twater Water temperature
VCO2 Cardio dioxide production
VE Expired ventilation VO2 Oxygen uptake
VO2peak Peak Oxygen uptake
VT Tidal volume
Contents
1 Introduction 1
1.1 Aim . . . 2
1.2 Hypothesis . . . 3
1.3 Significance of the study . . . 3
2 Methods 4 2.1 Ethics approval . . . 4 2.2 Subjects . . . 4 2.3 Experimental design . . . 5 2.4 Experimental procedure . . . 6 2.5 Measurements . . . 7 2.6 Data analyses . . . 9 2.7 Statistical analyses . . . 9 3 Results 10 3.1 Immersion in 14°C water . . . 10 3.2 Immersion in 21°C water . . . 17 4 Discussion 23 4.1 Specific adaptation . . . 24 4.2 Transfer adaptation . . . 26 4.3 Methodological considerations . . . 27
4.4 Practical perspectives and significance . . . 28
viii CONTENTS
4.5 Future work . . . 28
5 Conclusion 30 A Background 31 A.1 Human thermoregulation to cold . . . 31
A.1.1 Behavioural thermoeffectors . . . 31
A.1.2 Autonomic thermoeffectors . . . 32
A.1.3 Non-thermal factors that may affect thermoeffector responses . 32 A.2 Thermo-adaptive modifications induced by long-term exposure to cold 34 A.2.1 Cold habituation, or hypothermic adaptation . . . 34
A.2.2 Insulative adaptation . . . 35
A.2.3 Metabolic adaptation . . . 35
A.2.4 Behavioural adaptation . . . 36
A.2.5 Evidence of cold adaptation from population studies . . . 36
A.2.6 Evidence of cold adaptation from acclimatisation studies . . . 37
A.2.7 Evidence of cold adaptation from acclimation studies . . . 37
A.2.8 Potential determinants of adaptation to cold . . . 39
Chapter 1
Introduction
Modern humans (Homo sapiens), who are tropical animals, originated in Africa and have spread to some of the coldest and most extreme regions on Earth. In the process, they have displayed a large capacity to adapt to these cold environments. This has been primarily achieved by utilising thermo-behavioral actions in response to a perceived state of thermal discomfort, thus creating comfortable thermal microclimates (e.g. clothing, housing, heating). During exposure to cold, aside from the acute and long-term behavioural responses, thermal balance is also preserved through the activation of autonomic thermoeffectors, i.e. peripheral vasoconstriction, which attenuates heat loss, and shivering, which enhances endogenous heat production. However, there are situations in which the ability to thermoregulate adequately might be compromised (for instance, during exposure to cold and wet conditions), potentially leading to a drop in body core temperature (i.e. hypothermia). Clinical hypothermia is defined as a body internal temperature below 35°C, which can lead to detrimental long-term effects and even death [1, 2]. There are roughly 20,000 reported hypothermia related deaths per year in Britain, with many more unofficial and unreported cases, particularly in the elderly [3].
A number of studies have shown that, when temperate residents are exposed, either continuously or intermittently, for a prolonged period of time to low ambient temperatures, thermo-adaptive modifications develop [4, 5, 6, 7]. These responses describe three distinct patterns of cold adaptation: i) the hypothermic adaptation (or cold habituation), which is characterized by the attenuation of vasoconstriction and shivering, and the alleviation of thermal discomfort [8, 9]. ii) the insulative adaptation, which is characterised by an enhanced peripheral vasoconstriction [10], and iii) the
metabolicadaptation, which is described by an enhanced shivering and non-shivering
thermogenesis [4, 11].
2 CHAPTER 1. INTRODUCTION
The exact determinants of these cold adaptation patterns, however, are still unclear. It has been suggested that the development of a specific type of cold adaptation depends primarily on the severity of the cold stress imposed, as well as by the duration of the intervention [4]. Young et al. [10] have proposed that the amount of body-heat loss experienced during cold exposure might be the key determinant: that is, a metabolic habituation is typically ensued when the total amount of heat loss is insubstantial, whereas insulative and metabolic adaptations are often developed when the rate of heat loss is severe. However, other authors have proposed that these thermoregulatory adaptative patterns might not be mutually exclusive, but rather they might describe different phases of a gradual development of a complete cold adaptation, which conceivably is the metabolic adaptation [4, 12]. Moreover, it should not be ignored that, in many field studies (for instance in population and expedition-based studies; see Appendix A.2.5 and A.2.6 respectively), the pattern of cold adaptation developed might have been confounded by non-thermal stressors, such as the individuals’ nutritional habits and the degrees of exercise performed during the cold exposure [12, 13].
It is well-known that, during acute cold stress, the threshold for and the magnitude of each thermoeffector response is dependent on various individual non-thermal factors, including: anthropometric characteristics (i.e., body fat), sex, age and fitness level [4, 14, 15, 16]. It is noteworthy, however, that the studies investigating the long-term adaptations to cold typically present and discuss only the average responses of the group exposed; yet, whether all individuals adapt to cold in a similar manner remains often unclear.
1.1 Aim
CHAPTER 1. INTRODUCTION 3
1.2 Hypothesis
It was hypothesised that the 5-day whole-body cold-water immersions would induce a hypothermic adaptation (habituation), which would be evident during both the severe and the moderate cold stress exposures. This adaptation would be characterised by a delay in the threshold for shivering, a reduction in the shivering intensity, an attenuation in the magnitude of cold-induced vasoconstriction, and an alleviation of the perceived thermal discomfort. Finally, a large inter-individual variation in the direction and the magnitude of the thermoregulatory responses was anticipated.
1.3 Significance of the study
Chapter 2
Methods
2.1 Ethics approval
The experimental protocol was approved by the Human Ethics Committee of Stockholm (2019-05729; see Appendix B) and conformed to the standards set by the Declaration of Helsinki. All subjects were informed in detail about the experimental procedures and were made aware that they could terminate their participation at any time of the study, before giving their written consent to participate. The present study is part of a larger project investigating the effects of repeated whole-body cold stress on finger blood flow regulation during localised cooling.
2.2 Subjects
Six healthy male subjects with no previous history of cold injuries were recruited for the study. Subjects’ mean (standard deviation; SD) age, height, body mass, body surface area, total skinfold thickness, body fat volume and peak oxygen uptake (VO2peak)
were: 26 (1) years, 186 (5) cm, 82.0 (9.3) kg, 2.06 (0.13) cm2, 92 (33) mm, 12.8 (4.9)
% and 3.3 (0.8) L/min, respectively. All subjects were aerobically fit, as verified by an exhaustive cycling trial performed prior to the main experimental sessions. Five subjects were non-smokers; one subject was a light smoker (approx. 1-2 cigarettes per day), who was advised not to smoke prior to the sessions. None of the subjects were taking medication during the study.
CHAPTER 2. METHODS 5
2.3 Experimental design
The overall study was performed between December 2019 and March 2020 in a laboratory of the Division of Environmental Physiology at the KTH Royal Institute of Technology (Solna, Sweden). During a preliminary visit to the laboratory, subjects were thoroughly familiarised with the experimental equipment, procedures, and staff. The anthropometric measurements (i.e., body mass, height and body fat), and the graded cycling trial to exhaustion (VO2peak) were also performed.
Subjects completed seven whole-body cold-water immersions, which were con-ducted in an open-label manner (Figure 2.1): i) five immersions in 14°C water (severe cold), which were performed daily in five consecutive days, and ii) two immersions in 21°C water (moderate cold), which were performed three days prior to the first 14°C-water immersion, and two days after the fifth 14°C-14°C-water immersion. During all sessions, subjects only wore swimming trunks, and were submerged to the level of the xiphoid process (Figure 2.3). The environmental conditions in the laboratory were kept constant at 27 (0.3)°C room temperature, 25 (7)% humidity and 747 (14) mmHg barometric pressure. Subjects performed all water immersions at the same time of the day (either in the morning or in the afternoon), in order to reduce the influence of circadian rhythms. Subjects were asked to consume a light meal at least three hours before coming into the laboratory, and to refrain from performing strenuous exercise and consuming caffeine and alcohol, 12 hours prior to each trial.
6 CHAPTER 2. METHODS
Figure 2.2: Schematic representation of the experimental procedure for the 14°C-water immersion (A), and the 21°C-water immersion (B) sessions. Trec: rectal temperature, Tsk: skin temperature.
2.4 Experimental procedure
The experimental procedure is depicted in (Figure 2.2). Before each immersion, subjects were accustomed to the laboratory ambient conditions for ∼30 minutes, whilst subjects got changed, the rectal thermometer was placed, subjects’ weight was recorded, and instrumentation was conducted. Each trial began with a 20-minute baseline (BL phase), during which subjects rested on a gurney adjacent to the immersion tank for 20 minutes. Following the BL phase, subjects entered directly into the tank, which was filled with stirred water maintained at 14°C or at 21°C (body cold-water immersion phase - BCW phase). The subjects quickly assumed a semi-upright sitting position, whilst both arms were supported at heart level, above the water surface (Figure 2.3). The left hand was subjected to room temperature. To address an additional question that is not presented herein, the right hand was placed in a custom-made temperature-controlled glove, which maintained the skin temperature at ∼35.5°C. The 14°C-water immersion lasted for a maximum of 120 minutes, or until the subjects’ rectal temperature (Trec)
dropped below 35°C. The 21°C-water immersion lasted until subjects’ Trecdropped by
CHAPTER 2. METHODS 7
Figure 2.3: A subject during a whole-body immersion in either 14°C or 21°C water.
2.5 Measurements
Graded exercise test and anthropometry. Subjects’ VO2peak was estimated by
a graded exhaustion trial performed on a bike ergometer (Daum, Electronic, Furth, Germany). The subjects pedaled at 60 W for 2 minutes, and thereafter the load was increased by 25 W/min until exhaustion. Body mass (accuracy 0.01 kg) was recorded using an electronic scale (Vetek, Väddo, SE). Body surface area (AD) was derived from measurements of body mass and height [17]. Thickness of skinfolds was assessed with a caliper (Harpenden, UK) at seven locations: the triceps, subscapular, chest, suprailiac, abdomen, anterior thigh, and midaxillary. [18].
Thermometry. Trec, which served as an indication of the body core temperature,
was recorded continuously using a rectal thermistor probe (Yellow Springs Instruments, Yellow Springs, OH, USA) inserted to a depth of 10 cm beyond the anal sphincter. Skin temperatures (Tsk) were recorded with copper-constantan (T-type) thermocouple
8 CHAPTER 2. METHODS
interpreted to measure temperature [19]. The primary insulation of the thermocouples was polytetrafluorethylene; the non-insulated welded thermocouple junctions were attached directly to the skin covered with air-permeable transparent film dressing (3M Health Care, St. Paul, USA). All temperatures were sampled every second with a data acquisition system NI USB-6215 (National Instruments, Austin, USA). All temperature probes were calibrated against a certified reference thermometer (Ellab, Copenhagen, Denmark) before each session.
Respiratory measurements. Throughout the sessions, subjected breathed through
a facemask (model 7450 Oro-Nasal V2 Mask, Hans Rudolph, Shawnee, OK). The facemask was connected with a metabolic unit (Quark PFT; Cosmed, Rome, Italy), and the following variables were monitored breath-by-breath: oxygen uptake (VO2),
cardon dioxide production (VCO2), respiratory exchange ratio (RER), tidal volume (VT),
respiratory frequency (RF) and expired ventilation (VE). The Quark PFT utilises a paramagnetic oxygen sensor, which analyses the exhaled gas by comparing the pressure differential of the exhaled gas to a reference sample through a magnetic field. The fluctuations in pressure difference are then converted into an electrical current, and used to assess the concentrations of inspired oxygen [20, 21, 22]
Arterial pressures and heart rate. Beat-to-beat systolic (SAP), diastolic (DAP),
and mean (MAP) arterial pressures were continuously obtained by finger photoplethys-mography (Finometer, Finapres Medical Systems BV, Amsterdam, The Netherlands) via a finger-cuff placed on the left middle finger, and with the reference pressure trans-ducer being placed at heart level. The Finometer employs a volume-clamp technique to measure finger arterial pressure using a combination of photodiode (infrared pho-toplethysmography light source and detector) clamped around the finger, and a small inflatable bladder. The photodiode emits infrared light that is partially absorbed by the blood and as the arterial pressure in the finger fluctuates (during heartbeats), the volume of infrared light that is absorbed/detected, varies, thus allowing an indirect measurement of the arterial pressure [23, 24, 25]. The calibration of the Finometer was performed before each immersion session, using a brachial cuff placed on the upper left arm, according to manufacturer instructions. The heart rate (HR) was derived as the inverse of the inter-beat interval from the arterial pressure curves obtained by the Finometer.
Perceptual measurements. During the BL (at 10-minute intervals) and the BCW
CHAPTER 2. METHODS 9
the subjects before each session.
2.6 Data analyses
Baseline values were calculated as averages of the final 10-min of the 20-min baseline phase. Due to the inter- and intra-individual variability in the duration of the immersion, all physiological data were expressed as a function of the absolute time completed by all subjects, including the corresponding final value.
The individual shivering thresholds, indicated by a sustained elevation in VO2,
were derived from the response of VO2 in relation to changes in Trec (∆Trec). Body
temperature (Tb) was calculated using the equation [26]:
Tb = 0.64 · Trec+ 0.36 · Tsk (2.1) Metabolic heat production (M) was calculated using the equation [27]:
M = (0.23 · RER + 0.77) · (5.873) · (V O2) · (60/AD) (2.2) where RER is the respiratory exchange ratio, VO2is oxygen uptake (in L/min), and AD
is the body surface area.
2.7 Statistical analyses
Chapter 3
Results
3.1 Immersion in 14°C water
All six subjects participated in all five sessions of the acclimation protocol. As presented in Table 1, four of the subjects completed the 120-min immersion period during all sessions. Two subjects, however, terminated the immersion prematurely, due to their Trecdropping below 35°C: one subject was removed from the water tank early in
all five sessions and the other in the last four sessions. The mean immersion duration was not significantly different (P > 0.58; Table 3.1).
Table 3.1: Actual water temperature (Twater), number of subjects completed the 120-min period (n), and mean duration of the five 14°C water immersions.
Note: Values are mean (SD) for Twater, and mean (range) for the duration.
ThermometryThe mean thermal responses obtained during each session are
sum-marised in Table 3.2. Baseline Trec, Tskand Tbdid not differ between the sessions (P
CHAPTER 3. RESULTS 11
≥0.22). The time course of ∆Trecduring the five immersions are depicted in Figure
3.1-A. The final values of Trecand ∆Trecwere similar between all sessions (P ≥ 0.16).
During the 5th session, the body core cooling rate was somewhat accelerated in four
subjects, but the difference was not significant (P = 0.52; Figure 3.1-B). Neither the mean (Figure 3.2), nor the final (Table 3.2) Tskdiffer between the sessions (P ≥ 0.17).
In five subjects, the final Tbwas slightly lower (∼0.21°C) in the 5ththan in the 1stsession
(P = 0.34).
Figure 3.1: The mean (SD) time course of changes in rectal temperature (∆Trec) relative to baseline (A), and the mean (SD) and individual (shaded dotted lines) of body core cooling rate (B) during the five 14°C water immersions.
C HAPTER 3. RESUL T S 12
Table 3.2: Thermal responses obtained during the five 14°C water immersions.
Note: Values are mean (range) for: rectal temperature (Trec), changes in rectal temperature from the respective baseline (∆Trec), as well as skin (Tsk) and body (Tb)
CHAPTER 3. RESULTS 13
Cardiorespiratory responses- The cardiorespiratory responses recorded during
each session are summarised in Table 3.3. During all cold-water immersions, subjects shivered, as it was indicated by the marked elevation in VO2(Figure 3.3-A) and M. In
comparison to the 1stsession, the cold-induced increase in VO
2appeared to be
dimin-ished in the last four sessions (Figure 3.3-B), albeit the difference was not statistically significant (P > 0.17). In particular, VO2 was lower in five subjects in session 2, in
four subjects in session 3, in five subjects in session 4 and in four subjects in session 5 (Figure 3.3-B). A similar pattern was also observed in M (P > 0.22; Table 3.3). In line with the observation of a lower VO2across the acclimation protocol, the perceived
shivering intensity also appeared to be diminished, especially during the session 5 (P > 0.15; Figure 3.4). Moreover, the threshold for shivering tended to be delayed in the last four sessions; yet a high inter- and intra-individual variability was observed (P > 0.18).
Table 3.4 summarises the mean and individual shivering thresholds.
Both VE and VCO2were slightly lower in the sessions 2 to 5 than in the session 1,
but the difference was not statistically significant (P ≥ 0.12). VT, RF and RER did not
differ between the five sessions (P ≥ 0.08; Table 3.3).
C HAPTER 3. RESUL T S 14
Table 3.3: Mean (range) values of the respiratory and cardiovascular responses obtained during the five 14°C water immersions.
Note: Values are mean (range) for: oxygen uptake (VO2), metabolic heat production (M), carbon dioxide production (VCO2), expired ventilation (VE), tidal volume
(VT) respiratory frequency (RF), respiratory exchange ratio (RER) systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR). * Significantly
C HAPTER 3. RESUL T S 15
16 CHAPTER 3. RESULTS
Figure 3.4: The mean (SD) and individual (shaded dotted lines) values of perceived shivering dur-ing the five 14°C water immersions.
Baseline SAP, DAP (Table 3.3) and MAP (Session 1 = 95 (8) mmHg, Session 2 = 92 (8) mmHg, Session 3 = 96 (8) mmHg, Session 4 = 91 (9) mmHg, Session 5 = 95 (6) mmHg) did not vary between the sessions (P ≤ 0.38). In comparison to session 1, the cold-induced elevation in MAP was blunted in all subjects during the sessions 2 (P = 0.03) and 5 (P = 0.06), whereas MAP did not vary substantially during the sessions 3 (P = 0.70) and 4 (P = 0.56) (Figure 3.5). Likewise, the cold-evoked increases in SAP and DAP were lower in sessions 2 and 3 than in session 1 (P ≤ 0.05; Table 3.3). Baseline HR did not differ between the trials (P = 0.15). During the immersion, HR was consistently lower in sessions 2 to 5 than in session 1 (P = 0.01; Table 3.3).
CHAPTER 3. RESULTS 17
Perceptions- During the immersion, the subjects felt cold and thermally
uncomfort-able (Figure 3.6). The cold acclimation protocol did not alter the sensation of coldness (P > 0.65; Figure 3.6-A). The cold-induced thermal discomfort was gradually reduced across the sessions, but the difference was not significant (P > 0.26; Figure 3.6-B). Furthermore, although no statistical significances were detected, subjects seemed to perceive the cold stimulus less painful [Session 1 = 2.2 (1.8), Session 2 = 1.7 (1.0), Session 3 = 2.1 (2.1), Session 4 = 1.7 (1.8) and Session 5 = 0.9 (0.7); P > 0.16] and to feel more pleasant [Session 1 = 0 (2.7), Session 2 = 0 (2.4), Session 3 = 0.5 (2.7), Session 4 = 0.75 (2.4) and Session 5 = 1.5 (2.6); P > 0.27] during the last sessions.
Figure 3.6: The mean (SD) and individual (shaded dotted lines) values of thermal sensation (A) and thermal comfort (B) during the five 14°C immersions
3.2 Immersion in 21°C water
Thermometry - The mean thermal responses obtained during the pre and post
sessions are summarised in Table 3.5. The duration of the immersion was 81 (45) min before and 77 (45) min after the acclimation protocol (P = 0.76). In one subject, during the post acclimation trial, Trecdropped only 0.3°C after 150 min of immersion. During
the post acclimation session, the body core cooling rate was somewhat accelerated in four subjects, but the difference was not significant (P = 0.27; Figure 3.7-B). Neither the mean (Figure 3.8), nor the final (Table 3.5) Tskdiffer between the sessions (P =
0.95).
Baseline Trec (P = 0.16) and Tb (P = 0.99) did not differ between the sessions.
Baseline Tsk was slighter higher (∼0.3°C) in the post session (P = 0.05). The time
18 CHAPTER 3. RESULTS
values of Trec, ∆Trecand Tbwere similar in the two sessions (P > 0.17). However, four
subjects displayed a lower final Tbin the post than in the pre session. Tskwas similar in
the two trials (P = 0.95; Figure 3.8); yet, a high inter-individual variability was observed, given that, in the post session, four subjects exhibited a decrease in the final Tsk, whereas
in two subjects Tskwas enhanced by ∼0.5-1°C .
Table 3.5: Thermal responses obtained during the 21°C water immersions pre and post the accli-mation protocol.
Note: Values are mean (range) for: rectal temperature (Trec), changes in rectal temperature from the
respective baseline (∆Trec), as well as skin (Tsk) and body (Tb) temperature.
CHAPTER 3. RESULTS 19
Figure 3.8: The mean (SD) time course of skin temperature (Tsk; A), and the mean (SD) and indi-vidual (shaded dotted lines) values of skin temperature (B) during the 21°C water immersions pre and post the acclimation protocol.
Cardiorespiratory response- The mean cardiorespiratory responses are summarised
in (Table 3.6) (see below). Baseline VO2 and M were similar in the two sessions (P
≥0.55). During both immersions, VO2was increased; but, in five subjects, VO2 was lower by ∼0.05 L/min in the post than in the pre sessions (P = 0.07; Figure 3.9-B). A similar response was also observed in M (Table 3.6; P = 0.09). The perceived intensity of shivering was reduced in two subjects and remained unchanged in four subjects (P = 0.20;
Figure 3.10). The thresholds for shivering could not be analysed statistically, because
four subjects shivered during the pre session, but only one subject shivered during the post session (Table 3.7). Still, it appeared that the shivering threshold, if anything, was delayed after the acclimation protocol. VE, VCO2, RF and VT did not vary between
sessions (P > 0.38). RER was slightly increased in the post session, both during the baseline and the immersion (P = 0.05).
C HAPTER 3. RESUL T S 20
Table 3.6: Mean (range) values of the respiratory and cardiovascular responses obtained during the 21°C water immersions, pre and post the acclimation protocol.
Note: Values are mean (range) for: oxygen uptake (VO2), metabolic heat production (M), carbon dioxide production (VCO2), expired ventilation (VE), tidal volume
(VT) respiratory frequency (RF), respiratory exchange ratio (RER) systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR). * Significantly
CHAPTER 3. RESULTS 21
Figure 3.10: The mean (SD) and individual (shaded dotted lines) values of perceived shivering during the 21°C water immersions pre and post the acclimation protocol
Baseline HR, SAP, DAP (Table 3.6) and MAP [Pre = 96 (11) mmHg, Post = 95 (7) mmHg] did not differ between the sessions (P ≥ 0.12). Also, the cold-induced elevations in HR, SAP, DAP (Table 3.6) and MAP (Figure 3.11) were similar in the two sessions (P ≥ 0.13).
22 CHAPTER 3. RESULTS
Perceptions– During the immersion, subjects felt cool, and slightly uncomfortable.
During the post sessions, these ratings tended to be improved, and be shifted towards slightly cool (Figure 3.12-A), and comfortable (Figure 3.12-B) perceptions; yet no statistically significant differences were observed (P > 0.16). The 21°C water immersion did not evoke any pain [Pre = 0.2 (0.4), Post = 0.0 (0.0); P = 0.36]. Lastly, subjects felt somewhat more pleasant during the post immersion [Pre = 1.1 (2.5), Post = 1.6 (1.7); P = 0.40].
Chapter 4
Discussion
There is compelling evidence that repeated whole-body exposures to cold, during which a drop in skin and/or body-core temperature is induced, lead to cold adaptation [8, 9, 28, 29]. The severity and duration of the thermal strain imposed during the process, as well as the confounding influence of non-thermal factors (e.g., exercise, diet etc; see Appendix A.1.3) might determine the type of cold adaptation developed. The present study was designed to examine, in a small homogeneous group of non-acclimatised men and in controlled laboratory conditions, the inter-individual adaptive response to a short-term, high-intensity cold acclimation regimen. The study also sought to determine whether, or to what extent, any thermoregulatory modifications induced by the repeated severe cold stress would be transferred to acute moderate (21°C-water immersion) cold stress (i.e., “transfer” adaptation). To answer these research questions, subjects completed five daily static immersions in 14°C water, within a week.
The main finding of the present study was that the 5-day, high intensity cold acclimation regimen caused a hypothermic adaptation, which was characterised by a blunted shivering response, a lower pressure response, and the alleviation of thermal discomfort. These thermo-adaptive modifications were evident both during the severe cold stress (i.e., 14°C water), which was specific to the acclimation stimulus, and during the moderate cold stress (i.e., 21°C water). Due to unforeseen circumstances (i.e., COVID-19), the experiments had to be stopped prematurely, resulting in a relatively small number of subjects completing the study; thus the data are discussed with some liberty, and from the scope of both statistical significances (P ≤ 0.05), as well as statistical tendencies (0.05 < P < 0.09) observed.
24 CHAPTER 4. DISCUSSION
4.1 Specific adaptation
The hypothermic adaptation is generally described by a gradual decrease in the intensity of the thermoeffector responses, and in particular the delayed activation of the shivering and/or vasoconstrictor responses [8, 9, 30, 31]. Young et al. [10, 29] have suggested that this adaptation pattern occurs when only limited parts of the body are exposed to cold, or when the total amount of whole-body heat loss is insubstantial. However, others [28, 31] have argued that a considerable size of deep-body cooling might be needed. In this study, a hypothermic adaptation was apparent in five subjects by the 5thcold-water immersion session; an accelerated body core cooling rate was noted.
These findings are in line with those observed in recent studies, which have applied a similar protocol as regards to the duration and intensity, i.e. repeated whole-body cold water (14 – 18°C) immersions of moderate duration (20 – 90 min) [28, 32, 33, 34]. Evidence for more pronounced physiological adjustments (for instance, the development of insulative or metabolic adaptations) is more commonly observed in studies involving, a longer overall period of intervention (i.e., > 3 weeks) with a larger number of repeated immersions (i.e., > 18 immersions) [29, 33, 35, 36]. These findings, therefore, suggest that the type of adaptation developed might be independent of the severity of the cold stimulus (or the degree of whole-body heat loss), but rather more dependent on the duration of the overall protocol, and the total number of repeated immersions.
In the present study, the faster body core cooling rate was resulted by a metabolic habituation, i.e.la diminished shivering-induced heat production, mainly due to a delayed shivering onset threshold. Interestingly, this was also in alignment with subjects’ per-ceived intensity of shivering, which was impaired during the course of the acclimation. The underlying mechanisms of the metabolic habituation are still largely hypothetical. It is assumed that, given that there were no changes in the administered water-temperature, as well as in subject’s Tsk, the response was probably not ascribed to any changes in the
function of the peripheral cold receptors. Presumably, the metabolic habituation was mediated by central modifications. This notion is indeed supported by animal-based research demonstrating that during short-term acclimation protocols, the metabolic habituation is deemed to be mediated primarily in the central nervous system [37, 38]. Similar indications have been provided by human studies as well [31, 35].
An acclimation-related reduction in the cold-induced M response has been observed to occur rapidly, and even without the employment of a severe cold stress (Castellani et al, 3, 20°C showers in 1 day) [12]. Interestingly, in this study, a reduction in M was already observed during the 2ndsession in all subjects; yet, this trend was not maintained
by all throughout the intervention. For instance, during the 4th and 5thsession, subject 5
CHAPTER 4. DISCUSSION 25
cooling rate was accelerated. It is hard to explain this response, but it is assumed that, for some reason, the rate of heat loss was gradually increased in this individual. Additionally, although, in general, the shivering thresholds tended to gradually be delayed, in subject 2 the initiation of shivering occurred earlier in the repeated immersions than in the 1stimmersion. However, despite his earlier onset for shivering, the increase in M was
lower, indicating that, instead, the intensity of shivering was probably reduced; such a possibility is also supported by the lower perception for shivering.
Typically, the hypothermic adaptation is also characterised by a delayed or impaired vasoconstrictor response to cold [8, 9, 39]. Thus, after the adaptation, an increase in Tskmight be observed, facilitating a greater heat loss to the environment, and thereby
contributing to the acceleration of the body core cooling rate. In this study, however, no changes in Tskwere induced by the 5-day acclimation protocol. A slight, but consistent
drop in Tsk was detected in the 3rd session, which probably was associated with the
indications of somewhat enhanced sympathetic tone detected in this session (see next paragraph). Still, overall, the cold acclimation protocol did not modulate the peripheral temperature reactions to cold.
As expected [8, 10, 28, 40], the water immersion increased MAP. However, this cold-induced increase in pressure was gradually diminished across the 5 sessions, suggesting a reduction in the overall sympathetic drive response. This finding is indeed consistent with the hypothermic adaptation [41]. On the other hand, in the literature, the effect of acute cold-water immersion on heart rate is more perplexing: studies have shown either an increase [42], a decrease [43], or no change [30, 44]. Still, in comparison to the 1stsession, and in line with the MAP responses, the repeated 14°C-water immersions
caused, in all subjects, a reduction in HR in the 2nd, 4thand 5thsessions. It is noteworthy,
however, that, in the 3rdsession, both HR and MAP were increased, returning to the
levels of the 1st session; this was observed in four out of six subjects. It is hard to
understand this response, but a possible interpretation is that the apprehension and stress associated with the study returned as the subjects recognised they were only half-way through the experiment; such a notion was also supported by the personal discussions with the subjects, who pointed out that, psychologically, the 3rd session was the most
challenging.
Repeated cold water immersions over several days have been shown to reduce the magnitude of the cold shock response, which typically occurs at the initial phase of immersion [28, 45]. It is interesting that a similar pattern was observed in the current study: the initial increase in VO2 was progressively reduced after the 3rd immersion,
26 CHAPTER 4. DISCUSSION
In the present study, the 14°C water invoked sensations of thermal discomfort and displeasure, as well as a transient sensation of moderate pain. Thermal perceptions, which initiate and coordinate conscious thermoregulatory behaviour, relies on the internal processing of thermo-afferent information from central (i.e., Trec) and peripheral (Tsk)
thermal cues [46, 47]. Yet, by the current study, it is impossible to deduce the relative contribution of each thermal input (i.e., Trecvs. Tsk) on the thermal discomfort [46].
Recent studies have indicated that the thermal sensation is influenced mainly by thermal cues from the skin [48, 49]. Still, it appears that, the alleviation of thermal discomfort and pain observed after the acclimation was independent of the absolute values of Tsk
and Trec, which did not vary between sessions. It is likely therefore that the cold induced
reduction in thermal discomfort was attributed to gradual adjustments in the central neutral circuits that regulate thermal sensation and comfort. However, whether these perceptual adaptations reveal a protocol-related habituation, or simply a familiarisation with the experimental protocol remains unknown.
4.2 Transfer adaptation
In line with previous studies, it appears that the adaptation to severe cold was transferrable to a moderate cold environment [29, 50]. It is noteworthy that, the subjects, who displayed a more rapid body core cooling rate during the 14°C-water immersions, were the only ones that displayed a similar body core cooling rate acceleration during the 21°C immersion. Thus, a metabolic habituation was demonstrated in both cold stimuli; VO2and M were reduced, and the shivering thresholds were delayed after the acclimation.
Notably, in one subject, the acclimation protocol altered neither his cooling rate nor his Tsk; yet, after the acclimation, the subject shivered significantly less. Gordon et al [50],
who have applied a similar experimental protocol and found a similar response, have suggested that this response might be an indication that the high-intensity acclimation protocol could have enhanced the activation of non-shivering thermogenesis, a response that is visible only during moderate cold exposure.
CHAPTER 4. DISCUSSION 27
4.3 Methodological considerations
Delimitations- In order to acquire a more homogeneous group, all subjects
par-ticipating in the project were young (24 – 28 years), Caucasian, non-heavy smokers, normotensive and aerobically fit men. Therefore, the results of this study should be lim-ited to this population. Furthermore, the study utilised cold water as a cooling medium to induce adaptation, and thus results and conclusions might not be applicable to other environmental conditions (i.e., cold air).
Limitations: An obvious limitation of the study is the small sample size (n = 6), providing insufficient power to draw any firm conclusions. However, as previously explained, this limitation was an unfortunate consequence of the unforeseen circum-stances of COVID-19 that terminated the experiments prematurely. The changes in internal body temperature were based on Trec, which is considered a slow indicator
[51, 52]. Also, since deviations in subjects’ postural position might cause variations in Trec[52], subjects’ body position was standardised across the study. Tskwas measured
via thermocouples, which are useful due to their high reliability and low cost. However, the thermocouples are known to have low accuracy, i.e., difficulties to achieve < 1°C of system errors [53]. Also, since subjects were immersed into the water, the thermo-couple recordings might reflect, to a large extent, the water temperature, rather than the actual skin temperature. The pressure and respiratory responses were monitored with the finger-cuff and the Quark PFT metabolic unit, respectively, which provide reliable indirect measures, but their accuracy is ∼±2% [54, 55]. Moreover, the use of breathing masks might also affect the ventilatory pattern [56]; yet it is assumed that its impact should be minute.
28 CHAPTER 4. DISCUSSION
limiting factor by hindering subjects’ abilities to fully express their perceptions. However, the question scales are typically deemed the most appropriate approach of measuring such perceptions in thermal physiology. Lastly, due to a lack of a control group, it cannot be excluded that any observed adaptative responses in thermo- perception might have been the result of a familiarisation effect to the experimental protocol, and to the scales.
4.4 Practical perspectives and significance
The present study indicates that a 5-day, high intensity acclimation protocol con-tributes to a hypothermic adaptation, mainly described by a more rapid body-core cooling rate due to a lower metabolic heat production. Therefore, this adaptation might be inter-preted as disadvantageous, because, apparently, it might increase the risk of developing hypothermia. However, Bittel et al [57] have suggested that the hypothermic adaptation is perhaps the most advantageous adaptation pattern, since the delayed onset of shivering reduces the shivering-induced metabolic burden during sustained cold exposure. In line with this notion, Tipton et al [58] have shown that, after cold habituation, and when a critical internal temperature is reached (< 35.0°C) during acute cold exposure, an augmented shivering response is activated, which eventually seems to prevent the individual from being at an increased risk of hypothermia [36, 59]. Thus, it might be suggested that such a short-term cold intervention can be employed by individuals, who are often exposed to cold conditions (e.g. military personnel), in order to improve their dexterity (e.g., higher Tsk and delayed shivering) and moral (more comfortable
perceptions) during exposure to cold. It is noteworthy, however, that some indications of habituation emerged already in the 2ndacclimation session; suggesting therefore that
the benefits of such acclimation protocols could probably be achieved by interventions of significantly briefer duration.
4.5 Future work
CHAPTER 4. DISCUSSION 29
Chapter 5
Conclusion
Present findings demonstrate that, in young healthy men, a 5-day, high intensity, whole-body cold acclimation protocol causes a hypothermic habituation, which is charac-terised by blunted shivering and pressure responses, and by alleviated thermal discomfort. These thermo-adaptive modifications were evident during exposure to a severe cold stimulus being specific to the acclimation stimulus, but they also seem to be transferrable, to a large extent, to a moderate cold stimulus. Lastly, the direction and the magnitude of the adaptive response is described by a large inter-individual variability.
Appendix A
Background
A.1 Human thermoregulation to cold
Thermoregulation is the process that allows the preservation of thermal balance, and thus the maintenance of internal body temperature within a narrow window of ∼36.5 - 37.5°C [61]. This is achieved by controlling the rate of heat loss and heat production through the seamless recruitment of behavioural and autonomic thermoeffectors. How-ever, if the function of these thermoregulatory responses is inadequate, which can often be the case during exposure to a high heat loss environment (e.g. in cold-wet conditions), body core temperature drops (i.e., hypothermia), which can be life threatening.
A.1.1 Behavioural thermoeffectors
Humans have a large capacity to adapt to a broad range of thermal environments, primarily by utilising conscious thermo-behavioural actions, which are driven mainly by the perceived thermal discomfort [62]. Behavioural thermoregulation includes acute actions, such as wearing additional insulated clothing, creating fires and initiating physical activity, as well as long-term actions, such as building shelters, and migrating to warmer regions. These responses have been employed by humans throughout evolution. Over a million years ago, Homo-erectus were building huts and windbreaks from stones and branches, whilst the earliest evidence of the use of a fire as a source of light and heat comes from China in 600,000 BC [63]. Thermo-behavioural actions require little, to no metabolic energy, and are therefore preferred. However, there are situations where the potential to thermoregulate behaviourally is limited, and thus the adequate activation and function of the autonomic thermoeffectors is crucial.
32 APPENDIX A. BACKGROUND
A.1.2 Autonomic thermoeffectors
The main autonomic responses to cold are: (i) peripheral vasoconstriction and (ii) shivering and non-shivering thermogenesis (cold-induced thermogenesis; CIT). Cold-induced peripheral vasoconstriction is the process during which blood vessel muscular walls contract, resulting in the reduction of blood flow and temperature, and thus in the attenuation of heat loss to the environment. Cutaneous reflex vasoconstriction is initiated when the skin temperature drops below ∼34°C [64]. The intensity of vasoconstriction mirrors that of the cold stimulus applied, until a plateau is reached, after which further cooling fails to induce a further vasomotor response [65].
CIT consists of two main subgroups: the shivering thermogenesis and the non-shivering thermogenesis. In humans, non-shivering is the main defence mechanism against cold [66]. Shivering involves repeated rhythmic muscle contractions, which increase endogenous heat production. It describes a large range of muscle contractions intensities; from a barely perceptible tremor, to a vigorous trembling/shuddering [11]. Peak shivering intensities may increase the basal metabolic rate (BMR) by up to 5 times [66, 67, 68], and enhance the whole-body metabolic rate to over 350 W [69]. However, shivering is an energy consuming process, and thus sustained periods of shivering might lead to the depletion of the metabolic fuel stores [66]. Also, shivering may increase convective heat loss due to body oscillations [70] and, depending on its intensity and duration, might contribute to perceived thermal discomfort.
Non-shivering thermogenesis is defined as any increase in basal metabolic rate and heat production, which is not originated by any muscle activity. Instead, it occurs through the metabolism of the brown adipose tissue (BAT), and of the secreted adrenergic hormones. BAT seems indeed to play a role in the maintenance of thermal homeostasis in the small mammals, and in human infants. However, in adult humans the contribution of non-shivering thermogenesis appears to be minimal [70, 71]; BAT dissipates a small amount of energy in the form of heat, and it has been estimated to account for an increase of 2.5-5% in the BMR [72, 73].
A.1.3 Non-thermal factors that may affect thermoeffector
re-sponses
The threshold for and the magnitude of each thermoregulatory effector response to cold describes a large amount of inter-individual variability, which depends on various non-thermal factors, morphological and behavioural.
Anthropometry. A main determinant of individual variability of cold
APPENDIX A. BACKGROUND 33
[4]. In general, larger individuals present enhanced body core cooling rates, because they have a larger surface area for convective heat flux during cold exposure [74, 75]. All body tissues provide some form of insulation, but the adipose tissue (fat) has the highest thermal resistance of all [4]. Therefore, large levels of subcutaneous fat lower the thermal gradient between skin and surroundings, which in turn seems to prevent, or at least decelerate, the cold-induced reduction of body core temperature [8, 76, 77].
Sex. Any sex-associated thermoregulatory differences appear to be explained,
almost entirely, by the variations in anthropometric and body composition characteristics [14]. Women, in general, possess a higher composition of body fat than men, which might enhance their thermal insulation. However, when comparing men and women of equal subcutaneous fat thicknesses, women often have a larger surface area to mass ratio, which results in a more rapid core temperature decline [77]. No differences in shivering sensitivity or intensity have been found between men and women [78].
Age. The main age-depended differences in cold thermoregulation seem to occur
predominantly at both age extremes: neonates, children (up to 12 years) and the elderly (> 60 years). These age groups are at higher risk for hypothermia, mainly due to a diminished vasomotor function [15, 79]. They also have greater surface area to mass ratios compared to adults, which contributes to enhanced heat dissipation. Moreover, it appears that their thermo-behavioural response to cold are delayed and impaired [8, 80]. Lastly, the elderly exhibit a delay onset of shivering [4, 79], and they typically have low physical fitness, which presumably may accelerate the development of fatigue in the shivering-active muscles.
Fitness level and exertional fatigue. Physically fit individuals seem to have enhanced
34 APPENDIX A. BACKGROUND
A.2 Thermo-adaptive modifications induced by
long-term exposure to cold
When temperate residents are exposed, either continuously or intermittently, for a prolonged period of time to low ambient temperatures, thermoregulatory adaptative responses to cold are typically developed [4, 5]. In the literature, the development of three different patterns of cold adaptation have been described [6, 7, 13]:
A.2.1 Cold habituation, or hypothermic adaptation
Cold habituation is described by a decrease in the intensity of the thermoeffector response to a repeated cold stimuli [8, 9, 30, 31]. Namely, habituation to cold is typically characterised by:
• A blunted vasoconstrictor response: the onset and magnitude of cold-induced vasoconstriction is delayed and impaired, respectively.
• A blunted shivering response: the onset and intensity of shivering is delayed and impaired, respectively.
• An alleviation of thermal discomfort.
• An impaired cardiovascular stress response: the cold-induced rise in arterial pres-sure, heart rate and stress hormones (e.g. norepinephrine, cortisol) is attenuated [30, 40]
APPENDIX A. BACKGROUND 35
A.2.2 Insulative adaptation
The insulative adaptation is characterised by enhanced heat conservation mech-anisms during cold exposure [10]. Namely, it involves a more rapid, profound, and sustained peripheral vasoconstriction, resulting in a faster drop of skin temperature, thereby limiting heat loss to the environment [83, 84, 85]. Such a response has been attributable to an enhanced sympathetic nervous response driven by sustained exposure to cold [10].
Evidence for this type of adaptation has been demonstrated by Budd et al, who examined, in six men, the thermoregulatory responses to cold-air (10°C for 2 hours) before and after ten daily immersions in cold-water (15°C baths for 30-60 minutes). The subjects were able to maintain their rectal temperature, whilst exhibiting reductions in shivering and skin temperature. With no evidence of any non-shivering thermogenesis or a change in cutaneous circulation, the results were attributed to an increase in tissue insulation, mediated by an enhanced vascular response within the skeletal muscles and an enhanced vasoconstriction (i.e. insulative adaptation) [85].
A.2.3 Metabolic adaptation
36 APPENDIX A. BACKGROUND
A.2.4 Behavioural adaptation
It has been also suggested by some authors that a fourth type of cold adaptation may exist, which is characterised by modifications of certain thermo-behavioural actions. For instance, a few studies have shown that, when the ambient temperature drops, Northern Europeans seem to be more effective at protecting their extremities (e.g. wearing gloves, hats, scarves) than Southern Europeans, and subsequently reducing the risk for hypothermia and cold injuries [93, 94].
A.2.5 Evidence of cold adaptation from population studies
The term adaptation is defined as the process of change or adjustment in an or-ganism’s structure or habits, allowing it to becoming better suited to its environment. Thus, one way for researchers to study and understand how humans can adapt to cold climates, has been to investigate the thermoregulatory responses of different ethnical groups/populations.
Arctic Indians and Inuit who reside in cold regions and, during their daily activities (e.g. during hunting/trapping etc) are exposed directly to severe cold, able to maintain the same internal temperatures during acute cold stress as the non-acclimatised Caucasian men [95]. In addition, they exhibit increased hand skin temperatures, lower muscle temperatures and higher resting metabolic rates [10, 86]. The latter responses are associated with enhanced hand dexterity and comfort [95, 96].
Although the continent of Australia is known for its heat during summer, the inland semi desert environment has night temperatures that fall to < 5°C during winter (frequently < 0°C). The inhabitants of this region are the Australian Aborigines, who traditionally sleep around small fires in limited shelters, wearing minimal clothing, thus being exposed to low nocturnal ambient temperatures. In comparison to non-acclimatised Caucasians, the Aborigines display a unique ability to tolerate mild hypothermia. In particularly, they show lower levels of metabolic heat production, being associated with little to no shivering, and lower values of core and skin temperatures; thus, suggesting a hypothermic insulative adaptation. Notably, such an adaptation results in energy conservation, and is associated with alleviation of the perceived thermal discomfort [97, 98, 99].
APPENDIX A. BACKGROUND 37
of control of several confounding factors: for instance, the higher BMR of circumpolar residents has been attributed to their high protein diets [100], and the higher thermal conductance of Inuit has been linked to their body composition [100]. Lastly, it has become difficult to confirm these findings with recent population studies, due to the integration of these natives into modern society and the improvements in the standard of living [10].
A.2.6 Evidence of cold adaptation from acclimatisation
stud-ies
Acclimatisation to cold is the functional adaptations that occurs in a specific natural environment, for instance during Artic expeditions [30, 84]. Given that the ambient temperatures in the arctic can fall as low as -70°C during winter [40], Antarctic and Arctic expeditioners are confronted with a significant amount of cold stress. Various studies have been conducted, with a variety of results: (i) Four men working in Antarctica for 24 weeks, showed a greater ability to maintain their rectal temperature with minimal changes in skin temperature, arterial pressure or shivering. These responses suggested an insulative adaptation [30]. (ii) Eight men working in Antarctica for 53 days, showed a delayed onset of shivering, and higher forearm, finger and thigh skin temperatures, but no changes in rectal temperature [101]. (iii) Eight individuals, after they skied for 3 weeks across Greenland, developed a hypothermic-insulative adaptation, which was characterised by a lower rectal temperature, lower skin temperature, and no changes in metabolism[102]. In summary, these studies have provided a variety of cold-adaptation patterns, due to their large variations in the severity and durations of exposure, the pre-exposure individuals’ characteristics, the levels of physical exercise performed, and the nutritional and clothing strategies employed.
A.2.7 Evidence of cold adaptation from acclimation studies
38 APPENDIX A. BACKGROUND
A.2.7.1 Cold-air acclimation regimens
Table 1 summarises different cold-air acclimation protocols, which differ regarding
the applied severity of the stimulus and duration, as well as the outcome. As expected, the studies employing the lowest air temperatures had the shortest exposure durations.
In general, the shorter daily exposures (≤ 1 hour) to cold air have resulted in a metabolic habituation, being described by a delayed onset of shivering, but no marked alterations in rectal or skin temperatures [103, 104]. Studies employing longer exposures (> 2 hours), have led to reductions in shivering and body temperatures, i.e. a hypothermic adaptation [92, 105, 106]. A few cold-air studies have reported acclimation patterns beyond habituation. Scholander et al [107] reported a metabolic form of acclimation in 8 students who had spent six weeks camping in moderately cold temperatures in the Norwegian mountains. The students were instructed to only wear ‘lightweight summer clothing’ and provided minimal shelter at night. After returning to the laboratory, they exhibited an enhanced metabolic response to cold than the control subjects. However, the authors did not compare the campers’ metabolic responses before and after the trip, and thus it remains unclear whether the responses were resulted by the repeated cold air exposures.
A.2.7.2 Cold-water acclimation regimens
A common difficulty in the cold-air acclimation protocols, is that subjects are at high risk of developing local cold injuries. Therefore, to minimise the cold-related discomfort and prevent any injuries, these studies have employed protocols, wherein either the severity of cold stress is small, or the duration of exposure is short; which, in turn, had resulted in small reductions in body core temperature, thus being considered an inadequate stimulus for the induction of cold adaptation [10]. Thus, the majority of acclimation studies prefer to use cold water immersions. The advantage of using cold water is its high volume-specific heat capacity (3500 times that of air) and its high thermal conductivity (24 times greater than that of air) [58].
The initial reaction to sudden immersion into cold water is known as a “cold shock” response (CSR). The CSR includes tachycardia, a reflex inspiratory gasp, uncontrollable hyperventilation and reduced breath holding time [108]; responses that can increase an individual’s chances of aspirating water and thus drowning [45]. Repeated cold water immersions over several days seem to reduce the magnitude of CSR, producing a habituation effect [28, 45], which may be maintained up to 7-14 months [109].
APPENDIX A. BACKGROUND 39
single exposure and of the total intervention (Table 2). Repeated whole-body cold water (14 – 18°C) immersions of moderate duration (20 – 90 min) have resulted in delayed onsets and decreased intensity of shivering and vasoconstriction (i.e., hypothermic habituation adaptation [28, 32, 33, 34]). However, others have observed an aggravation of cold-induced skin temperature reductions, suggesting a hypothermic-insulative cold acclimation [33, 110].
Evidence for more pronounced physiological adjustments have only been observed in studies where a severe cold stimulus substantially reduced the internal body tempera-ture. Studies involving longer immersion durations (e.g., 120 min in 20°C-water), or moderate durations into colder water (e.g., 60 mins in 14°C-water) observed reductions in total metabolic response to cold [12, 29, 36].
Three independent studies have also demonstrated that the insulative adaptation evoked by repeated cold-water immersions can be transferred to cold-air exposure (transfer adaptation) [12, 29, 35]. In particular, Young immersed subjects wearing only nylon swimming trunks in 18°C water for 90 minutes, repeated five days a week for eight weeks [29]. The physiological responses to acute cold air (5°C) were monitored before and after the acclimation program, showing a reduction in subjects’ rectal temperatures, skin temperatures as well as an increased metabolic heat production response [29]. In addition, Muza et al, who employed a similar protocol as Young et al, found little to no increments in arterial pressure during cold-air exposure [59].
A.2.8 Potential determinants of adaptation to cold
40 APPENDIX A. BACKGROUND
Figure A.1: Flowchart demonstrating a theoretical model of different patterns of human cold ac-climations. [10]
According to the model, metabolic and insulative adaptations may occur when the cold stimulus is severe enough to induce deep body heat loss: the insulative adaptation prevails when the enhancement of metabolic heat production is not sufficient enough to prevent the body core temperature decline. Thus, it might be argued that the metabolic adaptation occurs when the encountered cold stimulus is mild or moderate, whereas the insulative adaptation occurs when the cold stress is more severe [4].
APPENDIX A. BACKGROUND 41
APPENDIX A . B A C K GR OUND 42
APPENDIX A . B A C K GR OUND 43
Bibliography
[1] J Castellani and A Young. Exertion-induced fatigue and thermoregulating in the cold. Comp Biochem Physiol A Mol Integr Physiol, 128(4):769–76, 2001. [2] J Castellani and A Young. Exertional fatigue and cold exposure: Mechanisms of
hiker’s hypothermia. Nutrition, and Metabolism, 32(4):793–798, 2007.
[3] D Reingardien˙e. Pathological and pathophysiological review of the cause of hypothermia. Medicina, 39:90–97, 2003.
[4] J Castellani and A Young. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure. Autonomic Neuroscience:
Basic and Clinical, 196:63–74, 2016.
[5] M Brazaitis, N Eimantas, L Daniuseviciute, D Mickeviciene, R Steponaviciute, and A Skurvydas. Two strategies for response to 14oc cold-water immersion.
PLoS One, 9:109020, 2014.
[6] H Hammel. Terrestrial animal in cold: recent studies of primitive man. American
Physiology Society, pages 413–434, 1964.
[7] C Piantadosi. The biology of human survival: Life and death in extreme environ-ments, 2003.
[8] Stocks J.M, Taylor N, Tipton M.J, and Greanleaf J. Human physiological responses to cold exposure. Aviat Space Environ Med, 75:444–57, 2004.
[9] K Andersen, J Hart, H Hammel, and H Sabean. Metabolic and thermal response of eskimos during muscular exertion in the cold. J. Appl Physiol, 18:613–618, 1963.
[10] A Young. Homeostatic responses to prolonged cold exposure: human cold acclimatization. pages 419–438, 1996.
46 BIBLIOGRAPHY
[11] H Kaciuba-Uscilko and J Greenleaf. Acclimatization to cold in humans, 1989. [12] J.W Castellani, A.J Young, M.N Sawka, and K.B Pandolf. B: Human
thermoreg-ulatory responses during serial cold-water immersions. J Appl Physiol: 85, 1:204–209, 1998.
[13] J Launay and G Savourey. Cold adaptations, industrial health: 47, 2009. [14] H Rintamäki. Human responses to cold. alaska medicine, 2007.
[15] Y Inoue, M Nakao, T Araki, and H Udea. Thermoregulatory responses of young and older men to cold exposure. Eur J Appl Physiol, 65:492–498, 1992.
[16] M Nystoriak and A Bhatnagar. Cardiovascular effects and benefits of exercise.
Front. Cardiovasc. Med, 5:135, 2018.
[17] D Bois and E Bois. The measurement of the surface area of adults. Proceedings
of the Society for Experimental Biology and Medicine, 12(1):16–18, 1914.
[18] A Jackson and M Pollock. Generalized equations for predicting body density. the british journal of nutrition, 1978.
[19] D Pollock. Thermocouples: Theory and Properties, pages 249–250. CRC Press, 1991.
[20] J Langton and A Hutton. Respiratory gas analysis. Continuing Education in
Anaesthesia Critical Care and Pain, 9(1):19–23, February 2009.
[21] H Mtaweh, L Tuira, A Floh, and C Parshuram. Indirect calorimetry: History, technology, and application. Front. Pediatr, 6:257, 2018.
[22] P Schoffelen and G Plasqui. Classical experiments in whole-body metabolism: open-circuit respirometry-diluted flow chamber, hood, or facemask systems. Eur
J Appl Physiol, 118:33–49, 2018.
[23] G Parati. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. 1:647–55, 1989.
[24] M Lyew and J Jamieson. Blood pressure measurement using oscillometric finger cuffs in children and young adults: a comparison with arm cuffs during general anaesthesia. Anaesthesia, 49(10):895–899, 1994.
BIBLIOGRAPHY 47
[26] A Burton. Human calorimetry: Ii. the average temperature of the tissues of the body: three figures. The Journal of Nutrition, 9:261–280, 1935.
[27] A Gagge, Richard Pharo, and R Gonzalez. Mechanisms of heat exchange: bio-physics and physiology. Comprehensive physiology, pages 45–84, 2010.
[28] C Golden and M Tipton. Human adaptation to repeated cold immersions. Journal
of Physiology, 396:349–363, 1988.
[29] A.J Young, S.R Muza, M.N Sawka, R.R Gonzalez, and K.B Pandolf. Human ther-moregulatory responses to cold air are altered by repeated cold water immersion.
J. Appl. Physiol, 60:1542–12548, 1986.
[30] G Budd and N Warhaft. Body temperature, shivering, blood pressure and heart rate during a standard cold stress in australia and antarctica. J. Physiol, 186:216– 232, 1966.
[31] M.J Tipton, H Wakabayashi, M.J Barwood, C.M Eglin, I.B Mekjavic, and N.A Taylor. Habituation of the metabolic and ventilatory responses to cold-water immersion in humans. Journal of thermal Biology, 38:24–31, 2013.
[32] M Radomski and C Boutelier. Hormone response of normal and intermittent cold-preadapted humans to continuous cold. J. Appl. Physiol, 53:610–616, 1982. [33] L Jansky, P Sramek, J Savlikova, B Ulicny, H Janakova, and K Horky. Change in
sympathetic activity, cardiovascular functions and plasma hormone concentrations due to cold water immersion in men. Eur. J. Appl. Physiol, 74:148–152, 1996. [34] J.M Stocks, M.J Patterson, D.E Hyde, K.D Mittleman, and N.A Taylor. Metabolic
habituation following repeated resting cold-water immersions is not apparent during low intensity cold-water exercise. J Physiol Anthropol, 20(5):263–267, 2001.
[35] C O’Brien, A.J Young, D.T Lee, A Shitzer, M.N Sawka, and K.B Pandolf. Role of core temperature as a stimulus for cold acclimation during repeated immersion in 20°c water. J Appl Physiol, 89:242–250, 2000.
[36] J Bittel. Heat debt as an index for cold adaptation in men. J. AppI. Physiol, 62:1627–1634, 1987.
48 BIBLIOGRAPHY
[38] P Hinckel and K Schröder-Rosenstock. Central thermal adaptation of lower brain stem units in the guinea-pig. Pflügers Archiv, 395:344–346, 1982.
[39] M Keramidas, R Kölegård, and O Eiken. In shackleton’s trails: Central and local thermoadaptive modifications to cold and hypoxia after a man-hauling expedition on the antarctic plateau. Journal of thermal biology, 73:80–90, 2018.
[40] M Tiina. Different types of cold adaption in humans. Frontiers in Bioscience, 2:1047–1067, 2010.
[41] K Harinath, A Malhotra, K Pal, R Prasad, and R Kumar. Ramesh chand sawhney, autonomic nervous system and adrenal response to cold in man at antarctica.
Wilderness and Environmental Medicine, 16(2):81–91, 2005.
[42] E Adolph and G Molnar. Exchanges of heat and tolerances to cold in men exposed to outdoor weather. Am. J. Physiol, 146:507–537, 1946.
[43] E Arnett and D Watts. Catecholamine excretion in men exposed to cold. J. appl.
Physiol, 15:499–500, 1960.
[44] G Budd. Effects of cold exposure and exercise in a wet, cold antarctic climate. J.
appl. Physiol, 20:417–422, 1965.
[45] M Tipton, F Golden, C Higenbottam, I Mekjavic, and C Eglin. Temperature dependence of habituation of the initial responses to cold-water immersion, 1998. [46] Z Schlader, S Stannard, and T Mündel. Human thermoregulatory behavior during rest and exercise - a prospective review. Physiology and Behavior, 99(3):269–275, 2010.
[47] M Keramidas. Interactions of mild hypothermia and hypoxia on finger vasoreac-tivity to local cold stress. American Journal of Physiology-Regulatory, Integrative
and Comparative Physiology, 317:418–431, 2019.
[48] G Mower. Perceived intensity of peripheral thermal stimuli is independent of internal body temperature. Journal of Comparative and Physiological Psychology, 90(12):1152–1155, 1976.
[49] Z Schlader. Orderly recruitment of thermoeffectors in resting humans.
Ameri-can Journal of Physiology-Regulatory, Integrative and Comparative Physiology,
BIBLIOGRAPHY 49
[50] K Gordon, D.P Blondin, B.J Friesen, H.C Tingelstad, G.P Kenny, and F Haman. Seven days of cold acclimation substantially reduces shivering intensity and increases nonshivering thermogenesis in adult humans, 2019.
[51] K Miller. Validity of core temperature measurements at 3 rectal depths during rest, exercise, cold-water immersion, and recovery. Journal of athletic training, 52:332–338, 2017.
[52] N Taylor, M Tipton, and G Kenny. Considerations for the measurement of core, skin and mean body temperatures. Journal of Thermal Biology, 2014.
[53] J Dalley, W Riley, and K Mcconnell. Instrumentation for engineering measure-ments, 1993.
[54] COSMED. Quark PFT User manual, VII Edition. Srl - Italy, vii edition, September 2003.
[55] FMS BV. Finometer User Guide, 1.10 edition, May 2002.
[56] F Golla and S Antonovich. The respiratory rhythm in its relation to the mechanisms of thought, 1929.
[57] J.H.M Bittel, G.H Livecchi-Gonnot, A.M Hanniquet, C Poulain, and J.L Etienne. Thermal changes observed before and after j.l etienne’s journey to the north pole.
Eur. J. Appl. Physiol, 58:646–651, 1989.
[58] M Tipton, N Collier, H Massey, J Corbett, and M Harper. Cold water immersion: kill or cure? experimental physiology: 102, 2017.
[59] S.R Muza, A.J Young, M.N Sawka, J.E Bogart, and K.B Pandolf. Respiratory and cardiovascular responses to cold stress following repeated cold water immersion.
Undersea Biomed. Res, 15:165–178, 1988.
[60] P Golja and I Mekjavic. Effect of hypoxia on preferred hand temperature. Aviat
Space Environ Med, 74:522–526, 2003.
[61] J Hutchinson, R Ward, J Lacriox, P Hebert, M Barnes, and D Bohn. Hypothermia therapy after traumatic brain injury in children. N Engl J Med, 358:2447–56, 2008.
