Dynamics Of Healthy Subjects Research Articles

Diffusion Tensor Imaging Along Perivascular Spaces (DTI-ALPS) to Assess Effects of Age, Sex, and Head Size on Interstitial Fluid Dynamics in Healthy Subjects.

Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic clearance is implicated in Alzheimer's disease (AD) pathophysiology. We assessed the contribution of age and female sex (strong AD risk factors) to DTI-ALPS index in healthy subjects. We also for the first time assessed the effect of head size. In accord with prior studies, we show reduced DTI-ALPS index with aging, and in men compared to women. However, head size may be a major contributing factor to this counterintuitive sex difference.

Induced Relaxation Enhances the Cardiorespiratory Dynamics in COVID-19 Survivors.

Most COVID-19 survivors report experiencing at least one persistent symptom after recovery, including sympathovagal imbalance. Relaxation techniques based on slow-paced breathing have proven to be beneficial for cardiovascular and respiratory dynamics in healthy subjects and patients with various diseases. Therefore, the present study aimed to explore the cardiorespiratory dynamics by linear and nonlinear analysis of photoplethysmographic and respiratory time series on COVID-19 survivors under a psychophysiological assessment that includes slow-paced breathing. We analyzed photoplethysmographic and respiratory signals of 49 COVID-19 survivors to assess breathing rate variability (BRV), pulse rate variability (PRV), and pulse-respiration quotient (PRQ) during a psychophysiological assessment. Additionally, a comorbidity-based analysis was conducted to evaluate group changes. Our results indicate that all BRV indices significantly differed when performing slow-paced breathing. Nonlinear parameters of PRV were more appropriate for identifying changes in breathing patterns than linear indices. Furthermore, the mean and standard deviation of PRQ exhibited a significant increase while sample and fuzzy entropies decreased during diaphragmatic breathing. Thus, our findings suggest that slow-paced breathing may improve the cardiorespiratory dynamics of COVID-19 survivors in the short term by enhancing cardiorespiratory coupling via increased vagal activity.

Effects of Exercise on Circulating Extracellular Vesicles in Cardiovascular Disease.

The evidence that physical exercise has multiple beneficial effects and is essential to a healthy lifestyle is widely accepted for a long-time. The functional and psychological changes promoted by exercise improve clinical outcomes and prognosis in several diseases, by decreasing mortality, disease severity, and hospital admissions. Nonetheless, the mechanisms that regulate the release, uptake, and communication of several factors in response to exercise are still not well defined. In the last years, extracellular vesicles have attracted significant interest in the scientific community due to their ability to carry and deliver proteins, lipids, and miRNA to distant organs in the body, promoting a very exciting crosstalk machinery. Moreover, increasing evidence suggests that exercise can modulate the release of those factors within EVs into the circulation, mediating its systemic adaptations.In this chapter, we summarize the effects of acute and chronic exercise on the extracellular vesicle dynamics in healthy subjects and patients with cardiovascular disease. The understanding of the changes in the cargo and kinetics of extracellular vesicles in response to exercise may open new possibilities of research and encourage the development of novel therapies that mimic the effects of exercise.

Contribution of Cardiorespiratory Coupling to the Irregular Dynamics of the Human Cardiovascular System

Irregularity is an important aspect of the cardiovascular system dynamics. Numerical indices of irregularity, such as the largest Lyapunov exponent and the correlation dimension estimated from interbeat interval time series, are early markers of cardiovascular diseases. However, there is no consensus on the origin of irregularity in the cardiovascular system. A common hypothesis suggests the importance of nonlinear bidirectional coupling between the cardiovascular system and the respiratory system for irregularity. Experimental investigations of this theory are severely limited by the capabilities of modern medical equipment and the nonstationarity of real biological systems. Therefore, we studied this problem using a mathematical model of the coupled cardiovascular system and respiratory system. We estimated and compared the numerical indices of complexity for a model simulating the cardiovascular dynamics in healthy subjects and a model with blocked regulation of the respiratory frequency and amplitude, which disturbs the coupling between the studied systems.

Utility of 4D Flow MRI in Thoracic Aortic Diseases: A Literature Review of Clinical Applications and Current Evidence.

Despite the recent technical developments, surgery on the thoracic aorta remains challenging and is associated with significant mortality and morbidity. Decisions about when and if to operate are based on a balance between surgical risk and the hazard of aortic rupture. These decisions are sometimes difficult in elective cases of thoracic aortic diseases, including aneurysms and dissections. Abnormal wall stress derived from flow alterations influences disease progression. Therefore, a better understanding of the complex hemodynamic environment inside the aortic lumen will facilitate patient-specific risk assessments of complications, which enable clinicians to provide timely prophylactic interventions. Time-resolved 3D phase-contrast (4D flow) MRI has many advantages for the in vivo assessment of flow dynamics. Recent developments in 4D flow imaging techniques has led to significant advances in our understanding of physiological flow dynamics in healthy subjects and patients with thoracic aortic diseases. In this clinically focused review of thoracic aortic diseases, we demonstrate the clinical advances acquired with 4D flow MRI from published studies. We provide a systematic overview of key evidences and considerations regarding normal thoracic aortas, thoracic aortic aneurysms, aortic dissections, and thoracic aortas with prosthetic graft replacement.

Spacetime in the brain: rapid brain network reorganization in visual processing and recovery

Functional connectivity networks (FCN) are the physiological basis of brain synchronization to integrating neural activity. They are not rigid but can reorganize under pathological conditions or during mental or behavioral states. However, because mental acts can be very fast, like the blink of an eye, we now used the visual system as a model to explore rapid FCN reorganization and its functional impact in normal, abnormal and post treatment vision. EEG-recordings were time-locked to visual stimulus presentation; graph analysis of neurophysiological oscillations were used to characterize millisecond FCN dynamics in healthy subjects and in patients with optic nerve damage before and after neuromodulation with alternating currents stimulation and were correlated with visual performance. We showed that rapid and transient FCN synchronization patterns in humans can evolve and dissolve in millisecond speed during visual processing. This rapid FCN reorganization is functionally relevant because disruption and recovery after treatment in optic nerve patients correlated with impaired and recovered visual performance, respectively. Because FCN hub and node interactions can evolve and dissolve in millisecond speed to manage spatial and temporal neural synchronization during visual processing and recovery, we propose “Brain Spacetime” as a fundamental principle of the human mind not only in visual cognition but also in vision restoration.

Gender-related specificities of photoplethysmogram spectral assessment dynamics in healthy subjects during the passive tilt test

The goal of our study was to investigate gender-related specificities of photoplethysmogram (PPG) spectral assessment dynamics in healthy individuals during the passive tilt test. Material and Methods — The study involved 38 men (33±7 years old) and 15 women (27±8 years old). The PPG signal was recorded for 10 minutes in the horizontal and vertical positions of the human body (passive tilt test). The following spectral parameters of PPG were calculated: HF%, LF%, and LF/HF. Results — In the horizontal body position, men had significantly higher values of the LF% index. In the course of the passive tilt test, an increase in HF% was observed by almost 1.5 times in men and by more than 5 times in women. Significant differences in the values of vegetative indicators were achieved: in women, HF% values exceeded those in men, while LF% values were noticeably lower. Conclusion — Men displayed signs (assessed by LF%) of augmented sympathetic activity, relative to women, at all stages of their passive tilt test. During the transition from the horizontal to the vertical position, a significant increase in respiratory influences (assessed by HF%) on PPG signal components was established, which was more pronounced in women.

Impaired Succinate Response to a Mixed Meal in Obesity and Type 2 Diabetes Is Normalized After Metabolic Surgery.

OBJECTIVETo explore the meal response of circulating succinate in patients with obesity and type 2 diabetes undergoing bariatric surgery and to examine the role of gastrointestinal glucose sensing in succinate dynamics in healthy subjects.RESEARCH DESIGN AND METHODSCohort I comprised 45 patients with morbid obesity and type 2 diabetes (BMI 39.4 ± 1.9 kg/m2) undergoing metabolic surgery. Cohort II was a confirmatory cohort of 13 patients (BMI 39.3 ± 1.4 kg/m2) undergoing gastric bypass surgery. Cohort III comprised 15 healthy subjects (BMI 26.4 ± 0.5 kg/m2). Cohorts I and II completed a 2-h mixed-meal tolerance test (MTT) before the intervention and at 1 year of follow-up, and cohort II also completed a 3-h lipid test (LT). Cohort III underwent a 3-h oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI) study.RESULTSIn cohort I, succinate response to MTT at follow-up was greater than before the intervention (P < 0.0001). This response was confirmed in cohort II with a greater increase after 1 year of surgery (P = 0.009). By contrast, LT did not elicit a succinate response. Changes in succinate response were associated with changes in the area under the curve of glucose (r = 0.417, P < 0.0001) and insulin (r = 0.204, P = 0.002). In cohort III, glycemia, per se, stimulated a plasma succinate response (P = 0.0004), but its response was greater in the OGTT (P = 0.02; OGTT versus IIGI).CONCLUSIONSThe meal-related response of circulating succinate in patients with obesity and type 2 diabetes is recovered after metabolic surgery.

Effect of Astaxanthin Supplementation on Psychophysiological Heart-Brain Axis Dynamics in Healthy Subjects

Objective: Marine microalgae is the predominant source of natural astaxanthin (NAX), a red-orange carotenoid with powerful antioxidant and anti-inflammatory properties. Previous studies suggest that NAX supplementation improves antioxidant capacity and reduces oxidative stress, while also enhancing fat utilization, exercise endurance, cardiovascular function, and neurological parameters. The purpose of this study was to assess the effects of NAX on the psychophysiological “heart-brain-axis” while nutrition (astaxanthin) may impact physiology (cardiovascular function) and psychology (mood state) in a coordinated manner.Methods: Using a double-blind parallel design, 28 healthy subjects (male=14, female=14, age=42) were supplemented for 8 weeks with NAX (12mg/day Haematococcus pluvialis algal extract) or a matching placebo. Before and after supplementation, subjects performed a cardiovascular stress test (VO2max) and completed a validated Profile of Mood States (POMS) survey to assess global mood state (GM) and related subscales: Vigor (V), Tension (T), Depression (D), Anger (A), Fatigue (F), and Confusion (C).Results: Subjects in the NAX group showed a significant ~10% lower average heart rate at submaximal exercise intensities compared to those in the placebo group (aerobic threshold, AeT; NAX 130+17 v. PL 145+14; and anaerobic threshold, AT; NAX 139+20 v. PL 154+11, p&lt;0.05). Significant improvements were found in the NAX group for both positive mood state parameters: GM (+11%, p&lt;0.05) &amp; V (+5%, NS); and negative mood state parameters: T (-20%, NS), D (-57%, p&lt;0.05), A (-12%, NS), F (-36%, p&lt;0.05), and C (-28%, NS). Conclusions: NAX supplementation lowered average heart rate at submaximal endurance intensities (suggesting a “physical” heart benefit) and improved mood state parameters (suggesting a “mental” brain benefit). While previous studies have shown NAX supplementation to improve parameters associated with heart health (antioxidant, fat oxidation, endurance) and brain health (neuro-inflammation, cognition, antidepressant/anxiolytic), these results suggest that natural astaxanthin supplementation supports the psychophysiological “heart-brain-axis” with simultaneous improvements in both physical and mental wellness.Keywords: Antioxidant; Carotenoid; Cardiovascular; Mood State; Mental Wellness

Association of long-term exposure to traffic-related PM10 with heart rate variability and heart rate dynamics in healthy subjects

BackgroundEpidemiological evidence on the influence of long-term exposure to traffic-related particulate matter (TPM10) on heart rate variability (HRV) is weak. ObjectiveTo evaluate the association of long-term exposure (10 years) with TPM10 on the regulation of the autonomic cardiovascular system and heart rate dynamics (HRD) in an aging general population, as well as potential modifying effects by the a priori selected factors sex, smoking status, obesity, and gene variation in selected glutathione S-transferases (GSTs). MethodsWe analyzed data from 1593 SAPALDIA cohort participants aged ≥ 50 years. For each participant, various HRV and HRD parameters were derived from 24-hour electrocardiogram recordings. Each parameter obtained was then used as the outcome variable in multivariable mixed linear regression models in order to evaluate the association with TPM10. Potential modifying effects were assessed using interaction terms. ResultsNo association between long-term exposure to TPM10 and HRV/HRD was observed in the entire study population. However, HRD changes were found in subjects without cardiovascular morbidity and both HRD and HRV changes in non-obese subjects without cardiovascular morbidity. Subjects without cardiovascular morbidity with homozygous GSTM1 gene deletion appeared to be more susceptible to the effects of TPM10. ConclusionThis study suggests that long-term exposure to TPM10 triggers adverse changes in the regulation of the cardiovascular system. These adverse effects were more visible in the subjects without cardiovascular disease, in whom the overall relationship between TPM10 and HRV/HRD could not be masked by underlying morbidities and the potential counteracting effects of related drug treatments.

Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40–50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20–49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s−1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

Symbolic time series analysis of electroencephalographic (EEG) epileptic seizure and brain dynamics with eye-open and eye-closed subjects during resting states

ObjectiveEpilepsy is a neuronal disorder for which the electrical discharge in the brain is synchronized, abnormal and excessive. To detect the epileptic seizures and to analyse brain activities during different mental states, various methods in non-linear dynamics have been proposed. This study is an attempt to quantify the complexity of control and epileptic subject with and without seizure as well as to distinguish eye-open (EO) and eye-closed (EC) conditions using threshold-based symbolic entropy.MethodsThe threshold-dependent symbolic entropy was applied to distinguish the healthy and epileptic subjects with seizure and seizure-free intervals (i.e. interictal and ictal) as well as to distinguish EO and EC conditions. The original time series data was converted into symbol sequences using quantization level, and word series of symbol sequences was generated using a word length of three or more. Then, normalized corrected Shannon entropy (NCSE) was computed to quantify the complexity. The NCSE values were not following the normal distribution, and the non-parametric Mann–Whitney–Wilcoxon (MWW) test was used to find significant differences among various groups at 0.05 significance level. The values of NCSE were presented in a form of topographic maps to show significant brain regions during EC and EO conditions. The results of the study were compared to those of the multiscale entropy (MSE).ResultsThe results indicated that the dynamics of healthy subjects are more complex compared to epileptic subjects (during seizure and seizure-free intervals) in both EO and EC conditions. The comparison of the dynamics of epileptic subjects revealed that seizure-free intervals are more complex than seizure intervals. The dynamics of healthy subjects during EO conditions are more complex compared to those during EC conditions. Further, the results clearly demonstrated that threshold-dependent symbolic entropy outperform MSE in distinguishing different physiological and pathological conditions.ConclusionThe threshold symbolic entropy has provided improved accuracy in quantifying the dynamics of healthy and epileptic subjects during EC an EO conditions for each electrode compared to the MSE.

QUANTITATIVE ANALYSIS OF THE MITRAL ANNULUS GEOMETRY AND FUNCTION IN HEALTHY VOLUNTEERS: A TRANSTHORACIC THREE-DIMENSIONAL ECHOCARDIOGRAPHY STUDY

Mitral valve (MV) quantitative analysis using 3D transthoracic echo (3DTTE) and dedicated software provides new insights into function of normal and pathological mitral annulus (MA). However, reference values for MA dimensions and dynamics in healthy subjects remain to be established. 224 healthy

Simulating CSF Flow Dynamics in the Normal and the Chiari I Subarachnoid Space during Rest and Exertion

CSF fluid dynamics in healthy subjects and patients with Chiari I have been characterized during rest with phase-contrast MR imaging and CFD. CSF flow velocities and pressures in the nonresting state have not been adequately characterized. We used computer simulations to study CSF dynamics during increased heart rates in the normal and Chiari I subarachnoid space. Cyclic CSF flow was simulated for multiple cycles in idealized 3D models of the subarachnoid space for normal and Chiari I malformation subarachnoid spaces, with flow cycles corresponding to 80 or 120 heart beats per minute. Flow velocities and pressures were computed by the Navier-Stokes equations. Synchronous bidirectional flow and flow patterns were displayed in Star-CD and inspected visually. Peak velocities and pressure differences in the 2 models were compared for the 2-cycle frequencies. Elevating the cycle rate from 80 to 120 cpm increased peak superior-inferior pressure gradients (top-bottom) by just 0.01% in the normal model and 2% in the Chiari model. Corresponding average pressure gradients increased by 92% and 100%, respectively. In addition, in both models, the range of synchronous bidirectional flow velocities increased. Systolic velocities had smaller increases with faster cycling. For each cycle rate, peak and average pressure gradients in the Chiari model were greater than in the normal model by 11%-16%. Raising the cycle rate from 80 to 120 cpm increased superior-inferior average pressure gradients and the range of synchronous bidirectional flow velocities in the normal and Chiari I models.

Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages.

Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk. Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow. Data were collected in 7 laboratories in 5 European countries. 180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years. None. Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent alpha1 show characteristic age dependence with a maximum around 50-60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by alpha2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for alpha2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake). The age dependence of alpha1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger alpha2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep.

Wavelet Analysis of the Frontal Auditory Evoked Potentials Obtained in the Passive Oddball Paradigm in Healthy Subjects and Schizophrenics

The goal of the present study was to apply the oscillatory brain dynamics model to the structural and quantitative analysis of neurocognitive functions considered as a potential marker of schizophrenia. This was achieved in tests of the detection of auditory events deviating in the regular auditory stream (oddball paradigm, MMN effect). It was hypothesized that the post-stimulus peaks of the oscillation power localized in post-stimulus time in the definite EEG oscillators represented neuro-electrical 'events' evoked in the specific neuronal nets characterized by this oscillation frequency band. We suggest that the time-frequency destination of these events related to the activation of the functional neuronal nets could be used for the determination of specific neurocognitive functions. Thus it was an attempt to distinguish the different neuro-functional parts of auditory processing and to compare these results between healthy subjects and patients with schizophrenia. The present results demonstrate the significant difference between the frontal averaged EEG oscillatory dynamics in healthy subjects and patients with schizophrenia related to neurocognitive function marked by the MMN and orienting response N200/P300a.

Cardiovascular dynamics in healthy subjects with differing heart rate responses to tilt

Orthostatic stress such as head-up tilt (HUT) elicits a wide range of heart rate (HR) and arterial pressure (AP) responses among healthy individuals. In this study, we evaluated cardiovascular dynamics in healthy subjects with different HR responses to HUT, but without autonomic dysfunction. We measured AP (brachial artery) and HR (ECG) during 5 min of 60 degrees HUT in 76 healthy normotensive individuals. We then chose individuals on the basis of the extremes of HR responses to HUT (high = DeltaHR > or = 20 beats/min, and low = DeltaHR < or = 10 beats/min; n = 15 per group). Peak HR during HUT was 87 +/- 10 beats/min in the high and 69 +/- 14 beats/min in the low group (P < 0.05). High HR responders had lower systolic pressure at baseline (121 +/- 9 vs. 129 +/- 11 mmHg, P < 0.05) and during HUT (120 +/- 10 vs. 131 +/- 13 mmHg, P < 0.05), and higher plasma norepinephrine (NE) response to HUT (DeltaNE: 156.9 +/- 17.8 vs. 89.0 +/- 17.2 pg/ml; P < 0.05). DeltaNE during HUT was also significantly correlated with DeltaHR when all 76 subjects were included in a regression analysis (r = 0.39; P < 0.001). Pulse pressure was lower during HUT in high HR responders compared with low HR responders (45 +/- 1 vs. 55 +/- 2 mmHg, P < 0.05). High HR responders also had larger fluctuations in systolic and pulse pressure during HUT (coefficient of variation = 10.7 +/- 0.7 vs. 5.7 +/- 0.3%; 7.9 +/- 0.5 vs. 4.1 +/- 0.4%, respectively, P < 0.05). Sex distribution was different between groups (high: 5 women, 10 men; low: 10 women, 5 men). Higher HR with lower AP during HUT is consistent with normal baroreflex mechanisms of integration. Although interindividual variability appears to be a fundamental part of cardiovascular regulation, the mechanisms of these differences and the sex discrepancy requires further investigation.

Cardiovascular dynamics in healthy subjects with differing heart rate responses to tilt

Orthostatic stress such as head‐up tilt (HUT) elicits a wide range of HR and BP responses among healthy individuals. In this study, we evaluated cardiovascular dynamics of subjects with different HR responses to HUT but without autonomic dysfunction. We measured BP (brachial artery) and HR (ECG) during 5 min of 60° HUT in 76 healthy young individuals, while norepinephrine (NE) was assayed during the final 30 s. We then chose 30 individuals based on the extremes of HR responses to HUT: 15 with the highest (ΔHR≥ 20 bpm) and 15 with the lowest response (ΔHR ≤10 bpm). Age and BMI were not different between groups; however, gender distribution was different (high: 5F, 10 M; low: 10F, 5M). Peak HR during HUT was 87.2±10.4 bpm in the high and 69.1±14.1 bpm in the low group (P&lt; 0.05). Baseline HR was not different between groups. High HR responders had lower SBP at baseline (120.9±9.4 vs. 129.4±11.0 mmHg) and during HUT (119.9±9.7 vs. 131.4±13.1 mmHg). High HR responders also had higher plasma NE response to HUT (ΔNE: 156.9±82.1 vs. 89.0±48.0 pg/ml; P&lt; 0.05). Higher HR with lower BP during HUT is consistent with normal baroreflex mechanisms of integration. Although inter‐individual variability appears to be a fundamental part of cardiovascular regulation, the mechanisms of these differences and the gender discrepancy requires further investigation.Supported by K23 RR17520, HL46493, NS32352, KL2 RR024151‐01.

Percutaneous application of carbon dioxide affects skin microcirculatory dynamics in healthy subjects

Objective: Bathing in carbonated springs is considered to dilate skin blood vessels and increase blood flow. We developed a plaster‐type carbon dioxide CO2‐sheet to apply on a topical skin area, and examined the microcirculatory dynamics of its application.Methods: CO2‐sheets containing different concentration of CO2 (250, 500, and 1000 ppm in solvent) were applied on the flexor aspect of the forearm of healthy subjects, and changes in the microcirculatory dynamics were studied by direct measurement of diameter of subepidermal microvessels using a Capillary Scope System, which irradiates the skin surface with indirect light. Local skin blood flow was measured by the venous occlusion method using near‐infrared spectroscopy, and also by two‐dimensional mapping using a full‐field laser profusion imager.Results: Compared with sham sheets, application of the CO2‐sheets significantly increased the diameter of subepidermal microvessels and increased the blood flow concentration‐dependently.Conclusions: This CO2‐sheets may be useful as a therapeutic device to improve skin microcirculation in the fields of health care as well as clinical medicine.

Circadian and Sex‐Dependent QT Dynamics

The dynamic QT relationship between the QT and RR intervals in normal individuals, including sex differences, has not been well examined. The aim of this Holter monitor-based study was to assess circadian and sex-related variations in QT dynamics in healthy subjects. The study population consisted of 50 healthy volunteers (mean age = 32 +/- 6 years, 25 men), in whom 24-hour digital Holter monitoring and QT interactive, beat-by-beat analyses were performed. The mean lengths of QT and RR intervals were measured from the 24-hour recordings. In order to assess QT dynamics, QT/RR linear regression was performed, and the slope was calculated over 24 hour and for day and night periods, and both genders separately. In the whole population, the mean QT interval was 356.5 +/- 19.2 ms and RR interval was 785.9 +/- 80.7 ms. The mean value of the slope over 24 hour was 0.17 +/- 0.03, though significantly steeper during the day (0.13 +/- 0.03) than at night (0.09 +/- 0.03, P < 0.001). The analysis of QT/RR dynamics over 24 hour revealed a significantly steeper slope in women (0.18 +/- 0.03) than in men (0.16 +/- 0.03, P = 0.006), as well as during daytime (0.14 +/- 0.03 vs 0.12 +/- 0.03, P = 0.04). Circadian variations and sex differences were observed in QT dynamics. The latter may explain the greater susceptibility of women to torsades de pointes during treatment with drugs that prolong repolarization.