The purpose of this study was to examine the effects of the cold pressor test on skin temperature, natural killer cell activity, plasma concentrations of interleukin-1 and cortisol, and the numbers of white blood cells, CD3+ cells, CD4+ cells, CD8+ cells, and CD56+ cells in the peripheral blood. In addition, the study examined whether thermal biofeedback, when presented following the cold pressor tests, would mitigate the effects of the cold pressor tests. Four male university students completed pretest psychological inventories and were pretrained during nine laboratory sessions to increase their skin temperature to 95 degrees Fahrenheit. During the experiment, blood samples were collected at 5-minute intervals and before and after the 1-minute cold pressor tests through an 18-mm catheter inserted into each subject's arm. Subjects were randomly assigned to a matched pair and to the order of experimental conditions, including baseline, the initial cold pressor test, return to baseline, the second cold pressor test, and thermal biofeedback. Each matched pair experienced the conditions in a multiple baseline fashion across subjects during the individual 1.5-hour experimental sessions. Following the experiment, subjects completed posttest psychological inventories, exit interviews, and consumer satisfaction surveys. All subjects demonstrated a decrease in skin temperature ranging from 1 to 1.4 degrees Fahrenheit during the 1-minute cold pressor tests in a multiple baseline fashion, and repeated the temperature decreases within-subjects during the second cold pressor test. Increases in natural killer cell activity ranged from 1% to 14% during the cold pressor tests. For all subjects, both cold pressor tests were associated with increased plasma concentrations of interleukin-1, ranging from 2 to 69 pg/ml. The initial cold pressor tests were associated with increases in all cell numbers in a multiple baseline fashion, but cell numbers varied during the second cold pressor tests. For all subjects, average skin temperatures during the thermal biofeedback conditions were from .3 to .9 degrees higher than during the return to baseline conditions. For all subjects, thermal biofeedback conditions were associated with from 2 to 8 (10^4 cells/ml) higher mean numbers of CD56+ cells than the return to baseline conditions. For 3 subjects, the thermal biofeedback conditions were associated with higher numbers of white blood cells, CD3+ cells, CD4+ cells, and CD8+ cells than the return to baseline conditions. Thermal biofeedback was associated with reductions of from .2 to 26 in the standard deviations of interleukin-1 values, and with a reduced range of cortisol values following the cold pressor tests. Few changes occurred in scores from pre- to posttest on the psychological tests. Subjects rated the goal of learning to relax as very important. All of the subjects stated that they would seek relaxation training for the treatment of a medical or psychological disorder if prescribed. Implications are discussed for design of research in psychoneuroimmunology, for measurement of immune system variables, and for potential clinical applications of these data.

För att bättre kunna förstå och hjälpa de som drabbas av långvarig smärtproblematik är detviktigt att applicera ett biopsykosocialt perspektiv. En tidigare studie föreslog att en vissskattning av smärtintensitet i ett cold pressor test (CPT) var en biomarkör för utvecklingen avlångvarig smärtproblematik. Denna studie syftade till att undersöka huruvida dennaföreslagna biomarkör, samt variansen i sammanlagd smärtintensitet under CPT, kan förklarasav uppfattad stress respektive utmattningssymtom, utöver demografiska faktorer ochsymtomkatastrofiering. Deltagarna (n = 35) genomförde ett CPT. CPT-skattningaranalyserades tillsammans med demografiska faktorer, symtomkatastrofiering, uppfattad stressoch utmattningssymtom i hierarkiska regressionsanalyser och hierarkiska binära logistiskaregressionsanalyser. Resultaten visade att högre grad av uppfattad stress predicerade lägresmärtintensitet, utöver övriga faktorer. Utmattningssymtom hade ingen signifikant effekt påsmärtintensitet. Inga undersökta faktorer kunde förklara den föreslagna biomarkören.Resultatet indikerar att det finns en suppressoreffekt där katastrofiering och uppfattad stresspåverkar varandra ömsesidigt. Detta visar på det komplexa biopsykosociala samspel sompåverkar upplevelsen av smärta. Denna komplexitet och interaktion är viktig att ha i åtankenär individer i riskzonen för att utveckla smärtproblematik ska identifieras. / In order to help and understand patients with chronic pain, it is important to apply abiopsychosocial perspective. One previous study proposed a specific rating in a cold pressortest (CPT) as a biomarker for the development of persistent pain. This study aimed to explorewhether this proposed biomarker, and the sum of pain intensity ratings during CPT, could beexplained by perceived stress and exhaustion symptoms respectively, above and beyonddemographic factors and symptom catastrophizing. The participants (n = 35) performed aCPT. CPT-ratings were analyzed, together with demographic factors, symptomcatastrophizing, perceived stress and exhaustion symptoms, using hierarchical regressionanalyses and hierarchical binary logistic regression analyses. The results showed that higherlevels of perceived stress predicted lower pain intensity, above and beyond the other variablesexamined. Exhaustion symptoms showed no significant effect on pain intensity. None of thevariables could explain the proposed biomarker. The results indicate a suppressor effectwhere symptom catastrophizing and perceived stress interact and influence each othersimultaneously. This highlights the biopsychosocial interplay which influences painexperience. This complexity and interaction is an important factor to consider in the processof identifying individuals who are at risk for developing persistent pain.

Motivation The prevalence of cardiovascular disease is on the increase in sub-Saharan Africa largely owing to lifestyle changes associated with urbanisation. Traditional diets are being replaced with diets high in saturated fat and sugar. In addition to the nutritional transition, urbanisation in developing African countries also contributes to a more sedentary lifestyle. Together these trends contribute to a higher prevalence of obesity and hypertension that are major risk factors for the development of cardiovascular disease. Adipose tissue is now widely recognised as an endocrine organ that secretes numerous inflammatory mediators as well as adipocytokines such as leptin. The primary role of leptin is to induce satiety after a meal and to suppress appetite. However, in recent years the role of leptin in the development of obesity-related cardiovascular disease has gained increasing attention and interest. Furthermore, leptin levels not only differ with regard to gender but also ethnicity. Africans have higher leptin levels than Caucasians due to higher subcutaneous fat in Africans. Furthermore, the prevalence of hypertension and stroke are also greater in the African population. Taken together, it is important to investigate mechanisms by which elevated leptin may contribute to the development of cardiovascular disease, especially in cardiovascular disease-prone Africans. Aim The general aim of this study is to increase our understanding of the role of leptin in cardiovascular disease development by investigating associations of leptin with markers of sympathetic activity, endothelial dysfunction, and cardiovascular reactivity and recovery in Africans and Caucasians. Methodology Data from the SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study was used and presented in the original research articles described in Chapter 2, 3 and 4. This study included 409 African and Caucasian schoolteachers working in the Potchefstroom district in the North West Province of South Africa. Groups were stratified by ethnicity, gender and ethnicity or obesity in order to demonstrate potential differences. We performed cardiovascular measurements and determined levels of leptin, renin, cortisol, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) and urinary albumin-to-creatinine ratio (ACR). Independent t-tests were done to compare means between groups and Chi-square tests to compare proportions. Pearson’s correlations were determined to investigate associations as well as partial correlations after minimal adjustment for potential confounders. Multiple regression analyses were performed to investigate independent associations of leptin with cardiovascular and biochemical markers according to the specific focus of each research manuscript. Results and conclusions of the individual manuscripts  Leptin may contribute to obesity-related hypertension through its sympatho-activating effects. In the first research article (Chapter 2), we compared mean leptin levels and markers of autonomic activity between Africans and Caucasians. We also investigated associations between markers of autonomic activity and leptin. Africans had higher leptin, body mass index, blood pressure and heart rate compared to Caucasians. Furthermore, Africans also demonstrated reduced heart rate variability that is indicative of autonomic imbalance. Markers of autonomic activity that collectively reflected sympathetic overactivity associated with leptin in both Africans and Caucasians, independent of significant covariates and confounders including body mass index. These findings suggest that leptin may contribute to the development of hypertension by inducing autonomic dysfunction.  Leptin exerts direct vascular effects and may thereby contribute to increased cardiovascular disease risk in the obese. We therefore investigated associations between circulating markers of endothelial dysfunction (PAI-1, vWF and ACR) and leptin in lean and obese groups, irrespective of ethnicity (Chapter 3). As expected, leptin and plasminogen activator inhibitor-1 antigen levels were higher in the obese group. We found no differences for von Willebrand factor antigen and urinary albumin-to-creatinine ratio. In the obese group, all markers of endothelial dysfunction were positively associated with leptin in univariate analysis. However, after full adjustment in multiple regression analyses, only the association with plasminogen activator inhibitor-1 remained significant. Higher leptin levels in the obese may possibly induce endothelial dysfunction through mechanisms related to thrombotic vascular disease.  Greater cardiovascular reactivity to stress and prolonged recovery thereafter associates with increased cardiovascular disease risk. In the final research article (Chapter 4), we therefore investigated the relationship between cardiovascular reactivity and recovery to acute stress, induced by the cold pressor test, and leptin in Africans and Caucasians. Africans demonstrated greater cardiovascular reactivity compared to Caucasians. Associations of blood pressure, stroke volume, cardiac output, total peripheral resistance and arterial compliance reactivity with leptin were investigated during the stressor application and 1, 3 and 5 minutes post-stressor. There were no independent associations between cardiovascular reactivity and leptin during the stressor, and a few correlations at 1 and 3 minutes post-stressor. Associations were mostly evident at 5 minutes post-stressor and in Africans. We argue that higher leptin levels relate to impaired post-stress recovery and thereby could contribute to hypertension development in Africans. General conclusion Elevated leptin relates to sympathetic overactivity, vascular damage and delayed post-stress recovery, and thereby could contribute to increased cardiovascular disease risk. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Motivation The prevalence of cardiovascular disease is on the increase in sub-Saharan Africa largely owing to lifestyle changes associated with urbanisation. Traditional diets are being replaced with diets high in saturated fat and sugar. In addition to the nutritional transition, urbanisation in developing African countries also contributes to a more sedentary lifestyle. Together these trends contribute to a higher prevalence of obesity and hypertension that are major risk factors for the development of cardiovascular disease. Adipose tissue is now widely recognised as an endocrine organ that secretes numerous inflammatory mediators as well as adipocytokines such as leptin. The primary role of leptin is to induce satiety after a meal and to suppress appetite. However, in recent years the role of leptin in the development of obesity-related cardiovascular disease has gained increasing attention and interest. Furthermore, leptin levels not only differ with regard to gender but also ethnicity. Africans have higher leptin levels than Caucasians due to higher subcutaneous fat in Africans. Furthermore, the prevalence of hypertension and stroke are also greater in the African population. Taken together, it is important to investigate mechanisms by which elevated leptin may contribute to the development of cardiovascular disease, especially in cardiovascular disease-prone Africans. Aim The general aim of this study is to increase our understanding of the role of leptin in cardiovascular disease development by investigating associations of leptin with markers of sympathetic activity, endothelial dysfunction, and cardiovascular reactivity and recovery in Africans and Caucasians. Methodology Data from the SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study was used and presented in the original research articles described in Chapter 2, 3 and 4. This study included 409 African and Caucasian schoolteachers working in the Potchefstroom district in the North West Province of South Africa. Groups were stratified by ethnicity, gender and ethnicity or obesity in order to demonstrate potential differences. We performed cardiovascular measurements and determined levels of leptin, renin, cortisol, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF) and urinary albumin-to-creatinine ratio (ACR). Independent t-tests were done to compare means between groups and Chi-square tests to compare proportions. Pearson’s correlations were determined to investigate associations as well as partial correlations after minimal adjustment for potential confounders. Multiple regression analyses were performed to investigate independent associations of leptin with cardiovascular and biochemical markers according to the specific focus of each research manuscript. Results and conclusions of the individual manuscripts  Leptin may contribute to obesity-related hypertension through its sympatho-activating effects. In the first research article (Chapter 2), we compared mean leptin levels and markers of autonomic activity between Africans and Caucasians. We also investigated associations between markers of autonomic activity and leptin. Africans had higher leptin, body mass index, blood pressure and heart rate compared to Caucasians. Furthermore, Africans also demonstrated reduced heart rate variability that is indicative of autonomic imbalance. Markers of autonomic activity that collectively reflected sympathetic overactivity associated with leptin in both Africans and Caucasians, independent of significant covariates and confounders including body mass index. These findings suggest that leptin may contribute to the development of hypertension by inducing autonomic dysfunction.  Leptin exerts direct vascular effects and may thereby contribute to increased cardiovascular disease risk in the obese. We therefore investigated associations between circulating markers of endothelial dysfunction (PAI-1, vWF and ACR) and leptin in lean and obese groups, irrespective of ethnicity (Chapter 3). As expected, leptin and plasminogen activator inhibitor-1 antigen levels were higher in the obese group. We found no differences for von Willebrand factor antigen and urinary albumin-to-creatinine ratio. In the obese group, all markers of endothelial dysfunction were positively associated with leptin in univariate analysis. However, after full adjustment in multiple regression analyses, only the association with plasminogen activator inhibitor-1 remained significant. Higher leptin levels in the obese may possibly induce endothelial dysfunction through mechanisms related to thrombotic vascular disease.  Greater cardiovascular reactivity to stress and prolonged recovery thereafter associates with increased cardiovascular disease risk. In the final research article (Chapter 4), we therefore investigated the relationship between cardiovascular reactivity and recovery to acute stress, induced by the cold pressor test, and leptin in Africans and Caucasians. Africans demonstrated greater cardiovascular reactivity compared to Caucasians. Associations of blood pressure, stroke volume, cardiac output, total peripheral resistance and arterial compliance reactivity with leptin were investigated during the stressor application and 1, 3 and 5 minutes post-stressor. There were no independent associations between cardiovascular reactivity and leptin during the stressor, and a few correlations at 1 and 3 minutes post-stressor. Associations were mostly evident at 5 minutes post-stressor and in Africans. We argue that higher leptin levels relate to impaired post-stress recovery and thereby could contribute to hypertension development in Africans. General conclusion Elevated leptin relates to sympathetic overactivity, vascular damage and delayed post-stress recovery, and thereby could contribute to increased cardiovascular disease risk. / PhD (Physiology), North-West University, Potchefstroom Campus, 2015

Previous research has shown that there are several components involved in how we perceive pain, e.g. social and psychological factors such as expectations of pain. A cold pressor experiment was conducted to investigate the impact of negative/positive information on pain perception. We also investigated if a cognitive conflict created by disconfirming information of a pain expectation influences the pain experience. 106 participants (49 men and 57 women) got to hold their hand in 5°C water for 1 minute. The main outcome variable was self-reported pain during the cold pressor test. The results show that participants receiving negative information perceived more pain than the group receiving positive information. There was no significant difference in pain perception between those who were confirmed or disconfirmed in an expectation, nor was there a difference in cognitive conflict between the two groups. This is a first attempt to explore pain and cognitive conflict and can work as an inspiration for further investigation. / Tidigare forskning har visat att det är flera komponenter involverade i en smärtupplevelse, bland annat sociala och psykologiska faktorer så som förväntningar. Ett kallvattenexperiment utfördes för att undersöka positiv/negativ information och dess påverkan på upplevelsen av smärta. Vi undersökte även om smärta påverkas av en kognitiv konflikt skapad av en disconfirmation av en smärtförväntning. 106 deltagare (49 män och 57 kvinnor) fick hålla sin hand i 5°C vatten i en minut. Vårt mätinstrument var själv-rapporterad smärta vid kallvattentestet. Resultatet visade att deltagare som fick negativ information upplevde mer smärta än de som fick positiv information. Det fanns ingen signifikant skillnad mellan de som blev disconfirmed och confirmed i sin förväntan och inte heller någon skillnad mellan grupperna i upplevd kognitiv konflikt. Detta första försök att undersöka smärta och kognitiv konflikt kan bli till en inspiration för vidare undersökningar.

The current study utilized an early-stage translational approach (Tashiro & Mortensen, 2006) to empirically test the immediate effect of a 15-minute mindfulness intervention on acute pain experience. The study employed a three-group, repeated measures experimental design with two active control conditions (sham mindfulness and attention control) and an analogue pain induction procedure (cold-pressor test). The sample consisted of 165 university students. Repeated measures analyses found an interaction effect between condition and time for subjective pain intensity and an interaction effect between gender and time for pain tolerance. Trends show that attention control increased pain intensity, whereas mindfulness decreased pain intensity. Females exhibited greater pain tolerance at post-intervention across conditions. Analyses yielded no significant differences between conditions among dependent variables of pain tolerance, state affect, or state anxiety. A moderate relationship was found between fear of pain and pain tolerance at pre-intervention, but failed to significantly moderate outcome in main analyses. Post-hoc analyses revealed a subset of "high pain tolerant" participants, who endorsed significantly higher trait mindfulness, lower fear of pain, and lower pain catastrophizing compared to the remainder of participants. Negative affect was related to increased pain intensity within the attention control condition. Suggestions for future research and clinical implications of research in this area are discussed.

The present study investigated the impact of certain and uncertain socialinformation on pain perception and memory. We hypothesized that theuncertain feedback group would experience higher pain intensity. Further, thatthe uncertain group would remember fewer pictures than the certain group.Participants were 42 undergraduate students from a medium-sized universityin Sweden who received, depending on group assignment, either certain oruncertain feedback about the pain intensity in the upcoming cold-pressor test.Following feedback, the participants performed two categorization tasksduring which they had to indicate whether the picture showed a living thing oran object. During the second task they also had to perform the cold-pressortest. Thirty minutes after the cold-pressor test participants performed asurprise recall test with regard to the pictures presented during thecategorization tasks. The two groups did not differ in self-reported uncertaintyabout their expectation of pain during the cold-pressor test but the uncertainfeedback group expected the cold-pressor test to be more painful than thecertain feedback group. We found no differences between the groups in eitherperception or recall. Finally, recall was impaired for pictures presentedduring the cold-pressor test, independent of group. In sum, our hypotheseswere not supported. Suggestion for future research is to manipulate thefeedback in another way to make it clearer for the participants. / Den aktuella studien utredde betydelsen av osäker och säker socialinformation för smärtintensitet och minne. Studiens hypotes var att den osäkragruppen skulle uppleva högre smärtintensitet och att den osäkra gruppenskulle komma ihåg mindre bilder än den grupp som fick säker information.Deltagarna var 42 studenter på ett medelstort universitet i Sverige, beroendepå vilken grupp de hamnade i fick de antingen osäker eller säker socialinformation om smärtintensiteten på det kommande kallvattentestet. Efter densociala informationen utfördes två kategoriseringsuppgifter där de skulle angeom en bild föreställde något levande eller ett objekt, både före och underkallvattentestet, med ett överraskande minnestest 30 minuter efterkallvattentestet på de bilder som visades under kategoriseringsuppgiften. Detvar ingen skillnad på grupperna i osäkerheten om deras förväntan avkallvattentestet. Däremot förväntade sig den gruppen som fick osäkerinformation att kallvattentestet skulle vara smärtsammare än de som fick densäkra informationen. Vi hittade ingen skillnad mellan grupperna i varkensmärtupplevelsen eller minnet. Till sist, minnet försämrades för bilderna sompresenterades under kallvattentestet, oberoende av vilken grupptillhörighetdeltagarna hade. För att summera så stöddes ingen av våra hypoteser. Förslagför kommande forskning är att manipulera hur den sociala informationen gesför att göra det mer tydligt för deltagarna.

Intolerance of uncertainty concerns how one views and reacts touncertainty, where one who’s highly intolerant would find it verydiscomforting when confronted with uncertain situations. The purposeof this study was to examine the associations between intolerance ofuncertainty, pain catastrophizing, emotion regulation andpsychopathic traits. These variables were to be examined in thecontext of a Beads Task and a Cold Pressor Test (CPT). Wehypothesized that there would be a positive significant associationbetween intolerance of uncertainty, pain catastrophizing, emotionregulation, psychopathic traits. We also hypothesized that there wouldbe a difference depending on the difficulty of the Beads Task. To doso, data was collected from 60 university students (32 females and 28males). The results showed that there was a significant, positiveassociation between intolerance of uncertainty, pain catastrophizing,emotion regulation and the Beads Task measurements. Some of theseresults were similar to previous studies. / Intolerans mot osäkerhet berör hur en person uppfattar och reagerarpå osäkerhet, där någon som är intolerant upplever osäkra situationersom obehagliga. Syftet med denna studie var att undersökaassociationerna mellan intolerans mot osäkerhet,smärtkatastrofiering, känsloreglering och psykopatiskapersonlighetsdrag. Dessa variabler undersöktes i sammanhang medBeads Task och ett Kallvattentest. Där några av hypoteserna var attdet finns positiva signifikanta associationer mellan intolerans motosäkerhet, smärtkatastrofiering, känsloreglering och psykopatiskapersonlighetsdrag. Vi hade också en hypotes att det kommer finnas enskillnad beroende på svårighetsgraden av Beads Task. För att göradetta samlades data in från 60 universitetsstudenter (32 kvinnor och28 män). Resultaten visade på en signifikant, positiv associationmellan intolerans mot osäkerhet, smärtkatastrofiering,känsloreglering och Beads Task-måtten. Några av dessa resultat varlikt de i tidigare studier.

Abstract The aim of the present study was to describe the effects of different types of cold exposures on blood pressure (BP) and heart rate (HR) and to test how these cold-induced effects are modulated by antihypertensive drugs representing different kind of mechanisms of action. The tested drugs represented the following antihypertensive drug subgroups: metoprolol from beta-blocking agents, carvedilol from alfa- and beta-blocking agents, lisinopril from angiotensin converting enzyme inhibitors, eprosartan from angiotensin II antagonists, amlodipine from calcium channel blockers and hydrochlorothiazide from diuretics. The main outcome measures were the levels and changes in systolic (SBP) and diastolic blood pressure (DBP) and HR before, during and after cold exposure. The normotensive and mildly hypertensive subjects were exposed either to –15°C for 15 minutes (with winter clothing), 5°C for 45 minutes (minimal clothing) or to a cold pressor test (CPT). Before measurements at –15°C, metoprolol, carvedilol, lisinopril, eprosartan, hydrochlorothiazide or placebo were given for a week in a double-blind and crossover manner. In one test procedure (5°C and CPT) the test subjects ingested amlodipine for three days or were without drug ingestion before the tests in a crossover manner. Both SBP and DBP were markedly increased by all types of cold exposure. Cold-induced rises of SBP/DBP were higher during the exposure to 5°C and –15°C (19–35/20–24 mmHg) than during CPT (13/16 mmHg). Metoprolol, carvedilol, lisinopril, eprosartan and amlodipine decreased the level of BP during the exposure to 5°C and –15°C compared to placebo or no drug. The antihypertensive drugs, with dosages used in this study, did not affect the cold-induced rise of BP compared to no drug or placebo. HR increased during CPT, but decreased during exposure to 5°C and –15°C. Metoprolol and carvedilol decreased HR during exposure to –15°C compared to placebo. The present study demonstrates for the first time the effects of antihypertensive drugs on BP in hypertensive subjects exposed to cold similar to normal outdoor exposure in winter. Although the magnitude of the cold-induced rise in BP was not affected by the drugs, the drug-induced decrease in the level of BP kept the peak values in the cold closer to the recommended threshold limit values. / Tiivistelmä Tutkimuksen tarkoituksena oli selvittää eri mekanismeilla vaikuttavien verenpainelääkkeiden vaikutusta verenpainevasteisiin ja sydämen lyöntitiheyteen kylmässä sekä verrata erilaisten kylmäaltistusten vaikutusta verenpaineeseen ja sydämen lyöntitiheyteen. Tutkitut lääkkeet edustivat seuraavia verenpainelääkeryhmiä: metoprololi beetasalpaajia, karvediloli yhdistettyjä alfa- ja beetasalpaajia, lisinopriili ACE-estäjiä, eprosartaani angiotensiini II antagonisteja, amlodipiini kalsiumestäjiä ja hydroklooritiatsidi diureetteja. Tärkeimmät mitatut vasteet olivat systolisen ja diastolisen verenpaineen ja sydämen lyöntitiheyden tasot ja muutokset ennen kylmäaltistusta, kylmäaltistuksen aikana ja sen jälkeen. Lisäksi mitattiin lämpötilavasteita ja tuntemuksia. Normo- ja hypertensiiviset koehenkilöt altistettiin joko –15°C:seen 15 minuutin ajaksi (talvivaatetuksessa), 5°C:seen 45 minuutin ajaksi (minimaalisella vaatetuksella) tai tehtiin ns. käden kylmävesitesti (CPT). Testisarjoissa (–15°C) metoprololi, karvediloli, lisinopriili, eprosartaani ja hydroklooritiatsidi tai plasebo annettiin viikon ajan kaksoissokko- ja vaihtovuoromenetelmällä. Yhdessä testisarjassa (5°C ja CPT) koehenkilöt ottivat amlodipiinia 3 päivän ajan tai olivat ilman lääkettä ennen testikertoja vaihtovuoroisessa järjestyksessä. Kaikki kylmäaltistustyypit nostivat merkittävästi sekä systolista että diastolista verenpainetta. Systolisen ja diastolisen verenpaineen nousu oli korkeampi koko kehon kylmäaltistuksissa (5°C tai –15°C) (19–35/20–24 mmHg) kuin ns. kylmävesitestissä (13/16 mmHg). Metoprololi, karvediloli, lisinopriili, eprosartaani ja amlodipiini laskivat verenpaineen tasoja koko kehon kylmäaltistuksessa verrattuna plaseboon. Yksikään verenpainelääkkeistä ei vaikuttanut merkittävästi kylmän aiheuttamaan verenpaineen nousuun verrattuna tutkimuskertaan ilman lääkettä tai plaseboon. Sydämen lyöntitiheys nousi ns. kylmävesitestin aikana, mutta laski koko kehon kylmäaltistuksissa (5°C ja –15°C). Metoprololi ja karvediloli laskivat sydämen lyöntiheyttä kylmäaltistuksessa (–15°C) verrattuna plaseboon. Tämä tutkimus kuvaa ensimmäistä kertaa, kuinka verenpainelääkkeet vaikuttavat verenpainetasoihin ja -vasteisiin kylmäaltistuksessa, joka simuloi tyypillisiä ulko-olosuhteita talvella. Vaikka lääkkeet eivät estäneet kylmän aiheuttamaa verenpaineen nousua, ne laskivat verenpaineen tasoa, jolloin verenpaine pysyi kylmässäkin lähempänä suositusrajoja.

Abstract The purpose of this study was to find out and compare the physiological effects of different types of non-hypothermic cold exposure tests in man. In whole-body cold exposures lightly clothed subjects were exposed to 10°C for 2 hours (single exposure), as well as repeatidly for 2 h and 1 h on ten successive days in separate studies. For local cold exposures, cold pressor tests (immersion into ice-cold water) of both hands and both feet were used. In whole-body cold exposures, several hormonal and metabolic parameters as well as cold sensations were measured. In local cold exposures the measured parameters were blood pressure, heart rate and skin temperatures. The single 2-h whole-body cold air exposure decreased rectal and skin temperatures and body heat content, but increased the metabolic rate. At the same time the serum noradrenaline concentration increased indicating a general activation of the sympathetic nervous system. Serum free fatty acid concentration increased whereas cortisol, GH and prolactin concentrations fell. No significant changes were found in serum concentrations of adrenalin, TSH, T3, T4, testosterone or LH. Serum total proteins were enhanced apparently due to cold-induced hemoconcentration. After repeating the 2-h whole-body cold exposure for five days the increase in serum noradrenaline level was markedly lower in the cold. At the same time hemoconcentration, judged from serum protein concentrations, was attenuated and the subjects became habituated to the cold sensations. However, the results showed that the repeated 1-h cold exposure in 10°C was not sufficiently intensive to reduce the noradrenaline response. Comparison of the hand and foot cold pressor tests to whole-body cold exposure tests showed that all tests caused significant increases in systolic and diastolic blood pressures, but that heart rate increased significantly only in the cold pressor test of feet. During the 2-h cold air exposure the heart rate fell. This caused a reduction in rate pressure product (RPP, the product of heart rate and systolic blood pressure). In both cold pressor tests the rate pressure product increased, indicating the enhancement of the O2-need in the heart muscle. The results showed no significant correlation in systolic or diastolic blood pressures between whole-body and local cooling of hands or feet. The lack of the association between local and whole-body cold exposure tests may be due to differences in severity and site of the tests: whole-body cold exposure tests cause general cold discomfort while cold pressor tests cause local cold pain. / Tiivistelmä Tämän tutkimuksen tarkoituksena oli selvittää ja verrata eri tyyppisten lievien kylmäaltistustestien fysiologisia vaikutuksia ihmiseen. Yksittäisessä koko kehon kylmäaltistuksessa koehenkilöt olivat kevyesti vaatetettuina kahden tunnin ajan 10°C:n lämpötilassa. Toistetussa koko kehon kylmäaltistuksessa koehenkilöt oleskelivat myös 10°C:n lämpötilassa kahden tai yhden tunnin ajan kymmenenä perättäisenä päivänä. Paikallisessa kylmäaltistuksessa käytettiin kylmävesitestiä (ns. cold pressor koe). Testi tehtiin sekä käsille että jaloille. Koko kehon kylmäaltistuksessa mitattiin useita hormonaalisia, aineenvaihdunnan ja lämpötasapainon vasteita, sekä verenpainetta ja sydämen syketiheyttä. Paikallisissa kylmäaltistuksissa mitattiin verenpainetta, sydämen syketiheyttä ja iholämpötiloja. Yksittäinen koko kehon kahden tunnin kylmäaltistus laski syvälämpötilaa, iholämpötiloja ja kehon lämpösisältöä. Samanaikaisesti kehon lämmöntuotanto kasvoi. Seerumin noradrenaliinipitoisuus lisääntyi ilmentäen sympaattisen hermoston tehostunutta aktivoitumista. Seerumin vapaiden rasvahappojen pitoisuus kasvoi, samoin kokonaisproteiinipitoisuus, mutta kasvuhormonin, kortisolin ja prolaktiinin osalta todettiin pitoisuuksien vähenemistä. Merkitseviä muutoksia ei tapahtunut seerumin adrenaliinissa, TSH:ssa, T3:ssa, T4:ssä, testosteronissa tai LH:ssa. Toistetussa kahden tunnin pituisessa kylmäaltistuksessa seerumin noradrenaliinipitoisuudessa tapahtunut kasvu oli merkitsevästi vähäisempää viiden päivän jälkeen. Samanaikaisesti seerumin proteiinipitoisuus kylmässä väheni ja kylmätuntemukset muuttuivat lievemmiksi. Sen sijaan yhden tunnin toistettu altistus 10°C:ssa ei ollut riittävän voimakas vähentämään kylmän aiheuttamaa veren noradrenaliinipitoisuuden kasvua. Verenpaineen ja sydämen syketiheyden reaktioita verrattiin samoilla koehenkilöillä yksittäisessä kahden tunnin koko kehon kylmäaltistuksessa ja kylmävesitesteissä. Kaikki nämä testit kohottivat merkitsevästi systolista ja diastolista verenpainetta. Sydämen syketiheys laski koko kehon kylmäaltistuksessa. Jalkojen kylmävesitestissä sydämen syketiheys nousi merkitsevästi, mutta käsien testissä tämä nousu ei ollut merkitsevä. Verenpaineen nousu koko kehon kylmäaltistuksessa ei korreloinut merkitsevästi paikallisissa kylmäaltistuksissa mitattuihin verenpaineen nousuihin. Selittävänä tekijänä tähän lienee näiden kylmäaltistusmuotojen erilaisuus. Lievä koko kehon kylmäaltistus aiheuttaa yleistä epämiellyttävyyttä, kun taas äkilliseen, nopean iholämpötilan laskun aiheuttamaan paikalliseen kylmäaltistukseen liittyy usein kiputuntemuksia.