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      Cardiac Repolarization and Autonomic Regulation during Short-Term Cold Exposure in Hypertensive Men: An Experimental Study

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          Abstract

          Objectives

          The aim of our study was to assess the effect of short-term cold exposure, typical in subarctic climate, on cardiac electrical function among untreated middle-aged hypertensive men.

          Methods

          We conducted a population-based recruitment of 51 hypertensive men and a control group of 32 men without hypertension (age 55–65 years) who underwent whole-body cold exposure (15 min exposure to temperature −10°C, wind 3 m/s, winter clothes). Conduction times and amplitudes, vectorcardiography, arrhythmias, and heart rate variability (autonomic nervous function) were assessed.

          Results

          Short-term cold exposure increased T-peak to T-end interval from 67 to 72 ms (p<0.001) and 71 to 75 ms (p<0.001) and T-wave amplitude from 0.12 to 0.14 mV (p<0.001) and from 0.17 to 0.21 mV (p<0.001), while QTc interval was shortened from 408 to 398 ms (p<0.001) and from 410 to 401 ms (p<0.001) among hypertensive men and controls, respectively. Cold exposure increased both low (from 390 to 630 ms 2 (p<0.001) and 380 to 700 ms 2 (p<0.001), respectively) and high frequency heart rate variability (from 90 to 190 ms 2 (p<0.001) and 150 to 300 ms 2 (p<0.001), respectively), while low-to-high frequency-ratio was reduced. In addition, the frequency of ventricular ectopic beats increased slightly during cold exposure. The cold induced changes were similar between untreated hypertensive men and controls.

          Conclusions

          Short-term cold exposure with moderate facial and mild whole body cooling resulted in prolongation of T-peak to T-end interval and higher T-wave amplitude while QTc interval was shortened. These changes of ventricular repolarization may have resulted from altered cardiac autonomic regulation and were unaffected by untreated hypertension.

          Trial Registration

          ClinicalTrials.gov NCT02007031

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          Most cited references37

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          Cold exposure and winter mortality from ischaemic heart disease, cerebrovascular disease, respiratory disease, and all causes in warm and cold regions of Europe. The Eurowinter Group.

          (1997)
          Differences in baseline mortality, age structure, and influenza epidemics confound comparisons of cold-related increases in mortality between regions with different climates. The Eurowinter study aimed to assess whether increases in mortality per 1 degree C fall in temperature differ in various European regions and to relate any differences to usual winter climate and measures to protect against cold. Percentage increases in deaths per day per 1 degree C fall in temperature below 18 degrees C (indices of cold-related mortality) were estimated by generalised linear modelling. We assessed protective factors by surveys and adjusted by regression to 7 degrees C outdoor temperature. Cause-specific data gathered from 1988 to 1992 were analysed by multiple regression for men and women aged 50-59 and 65-74 in north Finland, south Finland, Baden-Württemburg, the Netherlands, London, and north Italy (24 groups). We used a similar method to analyse 1992 data in Athens and Palermo. The percentage increases in all-cause mortality per 1 degree C fall in temperature below 18 degrees C were greater in warmer regions than in colder regions (eg, Athens 2.15% [95% CI 1.20-3.10] vs south Finland 0.27% [0.15-0.40]). At an outdoor temperature of 7 degrees C, the mean living-room temperature was 19.2 degrees C in Athens and 21.7 degrees C in south Finland; 13% and 72% of people in these regions, respectively, wore hats when outdoors at 7 degrees C. Multiple regression analyses (with allowance for sex and age, in the six regions with full data) showed that high indices of cold-related mortality were associated with high mean winter temperatures, low living-room temperatures, limited bedroom heating, low proportions of people wearing hats, gloves, and anoraks, and inactivity and shivering when outdoors at 7 degrees C (p 0.05 for mortality from ischaemic heart disease and cerebrovascular disease). Mortality increased to a greater extent with given fall of temperature in regions with warm winters, in populations with cooler homes, and among people who wore fewer clothes and were less active outdoors.
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            The human sympathetic nervous system: its relevance in hypertension and heart failure.

            Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. The achievement of this 'mechanisms to management' transition is at different stages of development with regard to the two disorders. Clinical translation is mature in cardiac failure, knowledge of cardiac neural pathophysiology having led to the introduction of beta-adrenergic blockers, an effective therapy. With essential hypertension perhaps we are on the cusp of effective translation, with recent successful testing of selective catheter-based renal sympathetic nerve ablation in patients with resistant hypertension, an intervention firmly based on the demonstration of activation of the renal sympathetic outflow. Additional evidence in this regard is provided by the results of pilot studies exploring the possibility to reduce blood pressure in resistant hypertensives through electrical stimulation of the area of carotid baroreceptors. Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in hypertension pathogenesis, and perhaps suggests a wider role for anti-adrenergic antihypertensives, such as the imidazoline drug class (moxonidine, rilmenidine) which act within the CNS to inhibit central sympathetic outflow, although the lack of large-scale outcome trials with this drug class remains a very material deficiency.
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              'Autonomic conflict': a different way to die during cold water immersion?

              Cold water submersion can induce a high incidence of cardiac arrhythmias in healthy volunteers. Submersion and the release of breath holding can activate two powerful and antagonistic responses: the 'cold shock response' and the 'diving response'. The former involves the activation of a sympathetically driven tachycardia while the latter promotes a parasympathetically mediated bradycardia. We propose that the strong and simultaneous activation of the two limbs of the autonomic nervous system ('autonomic conflict') may account for these arrhythmias and may, in some vulnerable individuals, be responsible for deaths that have previously wrongly been ascribed to drowning or hypothermia. In this review, we consider the evidence supporting this claim and also hypothesise that other environmental triggers may induce autonomic conflict and this may be more widely responsible for sudden death in individuals with other predisposing conditions.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                1 July 2014
                : 9
                : 7
                : e99973
                Affiliations
                [1 ]Center for Environmental and Respiratory Health Research, University of Oulu, Oulu, Finland
                [2 ]Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
                [3 ]Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland
                [4 ]Department of Exercise and Medical Physiology, Verve Research, Oulu, Finland
                [5 ]Institute of Health Sciences, University of Oulu, Oulu, Finland
                [6 ]Unit of General Practice, Oulu University Hospital, Oulu, Finland
                [7 ]Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland
                [8 ]Institute of Biomedicine, Department of Physiology and Biocenter of Oulu, University of Oulu, Oulu, Finland
                [9 ]Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland
                [10 ]Oulu City Hospital, Oulu, Finland
                [11 ]Finnish Institute of Occupational Health, Oulu, Finland
                [12 ]Department of Medicine, Oulu University Hospital, Oulu, Finland
                [13 ]Department of Applied Science, London South Bank University, London, England
                Johns Hopkins University SOM, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HH TVK MT AK HVH MM SKK KHH RA HR JJKJ TMI. Performed the experiments: HH MT AK HR JJKJ TMI. Analyzed the data: HH TVK MT AK HVH RB HR JJKJ TMI. Wrote the paper: HH TVK MT AK HVH MM SKK RB KHH RA HR JJKJ TMI.

                Article
                PONE-D-13-46093
                10.1371/journal.pone.0099973
                4077657
                24983379
                685431b1-ce73-4a1f-ae36-f7407ca1dd87
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 December 2013
                : 19 May 2014
                Page count
                Pages: 9
                Funding
                The study was funded through grants from the National Institute for Health and Welfare as well as Paavo Nurmi, Emil Aaltonen and Ida Montin Foundations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Physiology
                Electrophysiology
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Diseases
                Arrhythmia
                Clinical Medicine
                Clinical Trials
                Health Care
                Environmental Health
                Public and Occupational Health
                Vascular Medicine
                Blood Pressure
                Hypertension
                Research and Analysis Methods
                Research Design
                Clinical Research Design

                Uncategorized
                Uncategorized

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