Purported Self-Organized Criticality of the Cardiovascular Function: Methodological Considerations for Zipf's Law Analysis.

Self-organized criticality is a universal theory for dynamical systems that has recently been applied to the cardiovascular system. Precise methodological approaches are essential for understanding the dynamics of cardiovascular self-organized criticality. This study examines how the duration and quality of data recording affect the analysis of cardiovascular self-organized criticality, with a focus on the beat-by-beat heart rate variability time series obtained from seven healthy subjects in a standing position. Drawing a Zipf diagram, we evaluated the distribution of cardiovascular events of bradycardia and tachycardia. We identified tipping points for the distribution of both bradycardia and tachycardia events. By varying the recording durations (1, 2, 5, 10, 20, 30, and 40 min) and sampling frequencies (500, 250, and 100 Hz), we investigated their influence on the observed distributions. While shorter recordings can effectively capture cardiovascular events, they may underestimate the variables describing their distribution. Additionally, the tipping point of the Zipf distribution differs between bradycardia and tachycardia events. Comparisons of the distribution of bradycardia and tachycardia events should be conducted using long data recordings. Utilizing devices with lower sampling frequencies may compromise data fidelity. These insights contribute to refining experimental protocols and advancing our understanding of the complex dynamics underlying cardiovascular regulation.

Decision-Making in Patients with Vasovagal Syncope: A Preliminary Study.

The aim of this study was to evaluate the differences in performance during a decisional conflict task between subjects with emotional/blood phobia and those with an orthostatic vasovagal syncope. A total of 332 young subjects were included, from which 99 were excluded because of their condition or treatment. The subjects were classified into four groups depending on their responses to a questionnaire: 98 in a control group, 10 in an emotional/blood phobia syncope group, 38 in an orthostatic syncope group, and 87 in an unclear status group. This former group was excluded. The subjects performed a decisional conflict task to quantify their conflict-management ability. The task was the computer version of the Simon Task. Emotional/blood phobia syncope subjects showed a delayed reaction time when faced with decisional conflict in comparison with the control and orthostatic syncope subjects (55.8 ± 17.7 ms, 20.5 ± 4.9 ms, and 13.4 ± 9.2 ms, respectively, p ≤ 0.05). Our result suggests that emotional/blood phobia and orthostatic syncope are two clinical entities. Decisions could be a target of management in patients with emotional/blood phobia syncope. The altered decision-making of subjects with emotion/blood phobia syncope emphasized the role of higher cerebral functions in blood pressure control.

Autonomic Nervous System Influences on Cardiovascular Self-Organized Criticality.

Cardiovascular self-organized criticality has recently been demonstrated. We studied a model of autonomic nervous system changes to better characterize heart rate variability self-organized criticality. The model included short and long-term autonomic changes associated with body position and physical training, respectively. Twelve professional soccer players took part in a 5-week training session divided into "Warm-up", "Intensive", and "Tapering" periods. A stand test was carried out at the beginning and end of each period. Heart rate variability was recorded beat by beat (Polar Team 2). Bradycardias, defined as successive heart rates with a decreasing value, were counted according to their length in number of heartbeat intervals. We checked whether bradycardias were distributed according to Zipf's law, a feature of self-organized criticality. Zipf's law draws a straight line when the rank of occurrence is plotted against the frequency of occurrence in a log-log graph. Bradycardias were distributed according to Zipf's law, regardless of body position or training. Bradycardias were much longer in the standing position than the supine position and Zipf's law was broken after a delay of four heartbeat intervals. Zipf's law could also be broken in some subjects with curved long bradycardia distributions by training. Zipf's law confirms the self-organized nature of heart rate variability and is strongly linked to autonomic standing adjustment. However, Zipf's law could be broken, the significance of which remains unclear.

Factors Influencing the Prognosis of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term debilitating multisystem condition with poor prognosis. Studies that examined predictors of ME/CFS outcomes yielded contradictory results. We aimed to explore epidemiological and clinical prognostic factors of ME/CFS using operationalized criteria for recovery/improvement. Adult ME/CFS patients who attended the Internal Medicine Department of Angers University Hospital, Angers, France between October 2011 and December 2019, and were followed up until December 2020, were included retrospectively. Their medical records were reviewed for data collection. Patients were classified into two groups according to the presence or absence of recovery/improvement (R/I) and compared for epidemiological characteristics, fatigue features, post-exertional malaise severity, clinical manifestations, and comorbidities. The subgroups of recovered and significantly improved patients were then compared. 168 patients were included. Recovery and improvement rates were 8.3% and 4.8%, respectively. Older age at disease onset was associated with R/I (OR 1.06 [95% CI 1.007-1.110] (p = 0.028)), while diagnostic delay was inversely associated with R/I (OR 0.98 [95% CI 0.964-0.996] (p = 0.036)). The study findings confirmed the poor prognosis of ME/CFS and the deleterious effect of diagnostic delay on disease progression. Interestingly, being older at disease onset was associated with better outcomes, which offers hope to patients for recovery/improvement even at an advanced age.

Zipf's Law of Vasovagal Heart Rate Variability Sequences.

Cardiovascular self-organized criticality (SOC) has recently been demonstrated by studying vasovagal sequences. These sequences combine bradycardia and a decrease in blood pressure. Observing enough of these sparse events is a barrier that prevents a better understanding of cardiovascular SOC. Our primary aim was to verify whether SOC could be studied by solely observing bradycardias and by showing their distribution according to Zipf's law. We studied patients with vasovagal syncope. Twenty-four of them had a positive outcome to the head-up tilt table test, while matched patients had a negative outcome. Bradycardias were distributed according to Zipf's law in all of the patients. The slope of the distribution of vasovagal sequences and bradycardia are slightly but significantly correlated, but only in cases of bradycardias shorter than five beats, highlighting the link between the two methods (r = 0.32; p < 0.05). These two slopes did not differ in patients with positive and negative outcomes, whereas the distribution slopes of bradycardias longer than five beats were different between these two groups (-0.187 ± 0.004 and -0.213 ± 0.006, respectively; p < 0.01). Bradycardias are distributed according to Zipf's law, providing clear insight into cardiovascular SOC. Bradycardia distribution could provide an interesting diagnosis tool for some cardiovascular diseases.

Heart Rate Variability is Correlated with Perceived Physical Fitness in Elite Soccer Players.

Heart Rate Variability (HRV) has been typically used to monitor athletes' physical fitness readiness. The supine position maximizes parasympathetic tone, which is important for monitoring in continuous aerobic sports, however, this is not the case of team sports that rely on anaerobic intermittent bouts, thus increasing sympathetic activation and vagal withdrawal. We hypothesized that HRV during sympathetic activation and vagal withdrawal would be a useful marker to evaluate perceived physical fitness in team sports. HRV was measured in both supine and standing positions during the mornings of 4 match days in 14 professional players. The supine Root Mean Square of the Successive Differences (RMSSD), as well as spectral analysis indices were recorded. Perceived physical fitness was assessed after each match by means of a visual analogue scale (VAS). Supine RMSSD was moderately correlated with perceived physical fitness (rho = 0.416), however, larger correlations were observed for supine and standing spectral indices (rho > 0.5). Correlation between RMSSD and Total Power was very large, thus questioning the usual interpretation of RMSSD (rho > 0.7). Standing Spectral HRV analyses may be a useful method for evaluating perceived physical fitness in the context of team sports. RMSSD may reflect the overall variability of HR and not only the parasympathetic influence, as observed in the current study.

Altered Venous Function during Long-Duration Spaceflights.

Aims: Venous adaptation to microgravity, associated with cardiovascular deconditioning, may contribute to orthostatic intolerance following spaceflight. The aim of this study was to analyze the main parameters of venous hemodynamics with long-duration spaceflight. Methods: Venous plethysmography was performed on 24 cosmonauts before, during, and after spaceflights aboard the International Space Station. Venous plethysmography assessed venous filling and emptying functions as well as microvascular filtration, in response to different levels of venous occlusion pressure. Calf volume was assessed using calf circumference measurements. Results: Calf volume decreased during spaceflight from 2.3 ± 0.3 to 1.7 ± 0.2 L (p < 0.001), and recovered after it (2.3 ± 0.3 L). Venous compliance, determined as the relationship between occlusion pressure and the change in venous volume, increased during spaceflight from 0.090 ± 0.005 to 0.120 ± 0.007 (p < 0.01) and recovered 8 days after landing (0.071 ± 0.005, arbitrary units). The index of venous emptying rate decreased during spaceflight from -0.004 ± 0.022 to -0.212 ± 0.033 (p < 0.001, arbitrary units). The index of vascular microfiltration increased during spaceflight from 6.1 ± 1.8 to 10.6 ± 7.9 (p < 0.05, arbitrary units). Conclusion: This study demonstrated that overall venous function is changed during spaceflight. In future, venous function should be considered when developing countermeasures to prevent cardiovascular deconditioning and orthostatic intolerance with long-duration spaceflight.

Heart rate variability in the standing position reflects training adaptation in professional soccer players.

PURPOSE: To show that heart rate variability (HRV) in the standing position better reflects the way in which athletes adapt to training in so-called intermittent sports than the indicator of resting parasympathetic tone usually employed in endurance sports. METHODS: Twenty professional soccer players (intermittent sport) took part in a 5-week training session divided into three successive periods: "Warm-up", "Intensive training" and "Tapering". At the beginning and end of each of the three periods, a stand test was carried out and the heart rate was recorded, beat by beat (Polar Team 2). We analysed HRV to determine the indicator mostly used to demonstrate training adaptation in endurance sports (lnRMSSD supine, natural logarithm of root mean square of the successive differences) as well as indicators obtained by means of spectral analysis in both supine and standing position. RESULTS: A decrease in heart rate was observed in the supine position at rest during training (-5.2 ± 1.3 bpm) while lnRMSSD and spectral analysis indicators remained unchanged. The "Warm-up" caused an increase in spectral analysis total power in standing position which was further highlighted by "Tapering" (3.39 ± 0.09, 3.61 ± 0.08 and 3.65 ± 0.09 log ms(2), respectively). However, the autonomic changes are probably more complex than a change in autonomic activity or balance since spectral analysis autonomic indicators remained unchanged. CONCLUSIONS: HRV in the standing position could monitor training adaptation in intermittent sports contrary to the indicator usually employed in endurance sports. However, the significance of the HRV change in the standing position during training remains unclear.

Self-Organization of Blood Pressure Regulation: Experimental Evidence.

Blood pressure regulation is a prime example of homeostatic regulation. However, some characteristics of the cardiovascular system better match a non-linear self-organized system than a homeostatic one. To determine whether blood pressure regulation is self-organized, we repeated the seminal demonstration of self-organized control of movement, but applied it to the cardiovascular system. We looked for two distinctive features peculiar to self-organization: non-equilibrium phase transitions and hysteresis in their occurrence when the system is challenged. We challenged the cardiovascular system by means of slow, 20-min Tilt-Up and Tilt-Down tilt table tests in random order. We continuously determined the phase between oscillations at the breathing frequency of Total Peripheral Resistances and Heart Rate Variability by means of cross-spectral analysis. We looked for a significant phase drift during these procedures, which signed a non-equilibrium phase transition. We determined at which head-up tilt angle it occurred. We checked that this angle was significantly different between Tilt-Up and Tilt-Down to demonstrate hysteresis. We observed a significant non-equilibrium phase transition in nine healthy volunteers out of 11 with significant hysteresis (48.1 ± 7.5° and 21.8 ± 3.9° during Tilt-Up and Tilt-Down, respectively, p < 0.05). Our study shows experimental evidence of self-organized short-term blood pressure regulation. It provides new insights into blood pressure regulation and its related disorders.

Self-Organization of Blood Pressure Regulation: Clinical Evidence.

The pathogenesis of vasovagal syncope has remained elusive despite many efforts to identify an underlying dysfunction. Catastrophe theory explains the spontaneous occurrence of sudden events in some mathematically complex systems known as self-organized systems poised at criticality. These systems universally exhibit a power law initially described in earthquake occurrence: the Gutenberg Richter law. The magnitude plotted against the total number of earthquakes of at least this magnitude draw a straight line on log-log graph. We hypothesized that vasovagal syncope is a catastrophe occurring spontaneously in the cardiovascular system. We counted the number and magnitude (number of beats) of vasovagal reactions (simultaneous decreases in both blood pressure and heart rate on consecutive beats) in 24 patients with vasovagal symptoms during a head-up tilt test and 24 paired patients with no symptoms during the test. For each patient, we checked whether vasovagal reaction occurrence followed the Gutenberg Richter law. The occurrence followed the Gutenberg Richter law in 43 patients (correlation coefficient |r| = 0.986 ± 0.001, mean ± SEM) out of 48, with no difference between patients with and without symptoms. We demonstrated that vasovagal syncope matches a catastrophe model occurring in a self-organized cardiovascular complex system poised at criticality. This is a new vision of cardiovascular regulation and its related disorders.

Towards human exploration of space: the THESEUS review series on neurophysiology research priorities.

The THESEUS project (Towards Human Exploration of Space: a European Strategy), initiated within the seventh Framework Programme by the European Commission, aimed at providing a cross-cutting, life-science-based roadmap for Europe's strategy towards human exploration of long space missions, and its relevance to applications on Earth. This topic was investigated by experts in the field, in the framework of the THESEUS project whose aim was to develop an integrated life sciences research roadmap regarding human space exploration. In particular, decades of research have shown that altered gravity impairs neurological responses at large, such as perception, sleep, motor control, and cognitive factors. International experts established a list of key issues that should be addressed in that context and provided several recommendations such as a maximal exploitation of currently available resources on Earth and in space.

Noisy fluctuation of heart rate indicates cardiovascular system instability.

Heart rate spontaneously fluctuates despite homeostatic regulatory mechanisms to stabilize it. Harmonic and fractal fluctuations have been described. Non-harmonic non-fractal fluctuation has not been studied because it is usually thought that it is caused by apparatus noise. We hypothesized that this fluctuation looking like apparatus noise (that we call "noisy fluctuation") is linked to challenged blood pressure stabilization and not to apparatus noise. We assessed noisy fluctuation by quantifying the small and fastest beat-to-beat fluctuation of RR-interval by means of spectral analysis (Nyquist power of heart rate variability: nyHRV) after filtering out its fractal component. We observed nyHRV in healthy supine subjects and in patients with vasovagal symptoms. We challenged stabilization of blood pressure by upright posture (by means of a head-up tilt table test). Head-up position on the tilt table dramatically decreased nyHRV (0.128 ± 0.063 vs. 0.004 ± 0.002, p < 0.01) in healthy subjects (n = 12). Head-up position also decreased nyHRV in patients without vasovagal symptoms (n = 24; 0.220 ± 0.058 vs. 0.034 ± 0.015, p < 0.05), but not in patients with vasovagal symptoms during a head-up tilt table test (age and sex paired, 0.103 ± 0.041 vs. 0.122 ± 0.069, not significant). Heart rate variability includes a physiological non-harmonic non-fractal noisy fluctuation. This noisy fluctuation indicates low engagement of regulatory mechanisms because it disappears when the cardiovascular system is challenged (upright posture). It also indicates cardiovascular instability because it does not disappear in upright patients before vasovagal syncope, a transient failure of cardiovascular regulation.

Moderate exercise effects on orthostatic intolerance while wearing protective clothing.

INTRODUCTION: Wearing protective clothing can have deleterious effects on operational capacities and can cause non-compensable thermal stress. We studied the effects of moderate exercise on orthostatic tolerance while wearing protective clothing in eight healthy subjects tolerant to orthostatism. METHODS: Subjects performed a 60-min moderate exercise on a treadmill followed by a 45-min head-up tilt test. Subjects performed the moderate exercise either in a comfortable condition (control, CON) or wearing protective clothing (PRO) in a random order. RESULTS: Compared with the CON trial, exercise in the PRO trial induced higher body dehydration, heart rate, and rectal temperature and a decrease in plasma volume. Orthostatic tolerance was significantly reduced in the PRO trial (23.7 +/- 0.2 min) compared with the CON trial (40.7 +/- 1.0 min). Transition from supine to head-up position caused a significant decrease in blood pressure in the PRO compared with the CON. RR interval was smaller in the PRO trial compared with CON in both the supine and head-up positions. Spontaneous baroreflex sensitivity was decreased in the PRO, either supine or standing, compared to CON (4.6 +/- 0.5 ms x mmHg(-1) and 14.5 +/- 4.2 ms x mmHg(-1) in supine, and 3.3 +/- 0.6 ms x mmHg(-1) and 7.0 +/- 0.6 ms x mmHg(-1) in standing, for PRO and CON, respectively). DISCUSSION: These results suggest that the large decrease in the tolerance to orthostatism after exercise while wearing protective clothing was due to the impossibility of maintaining an adapted blood pressure induced by a conflict between the needs of peripherical vasoconstriction linked to the standing posture, the needs of vasodilatation linked to thermoregulation, and a drop in the sensibility of the spontaneous baroreflex.

Skin vascular resistance in the standing position increases significantly after 7 days of dry immersion.

Actual and simulated microgravity induces hypovolemia and cardiovascular deconditioning, associated with vascular dysfunction. We hypothesized that vasoconstriction of skin microcirculatory bed should be altered following 7 days of simulated microgravity in order to maintain cardiovascular homeostasis during active standing. Eight healthy men were studied before and after 7 days of simulated microgravity modeled by dry immersion (DI). Changes of plasma volume and orthostatic tolerance were evaluated. Calf skin blood flow (laser-Doppler flowmetry), ECG and blood pressure signal during a 10-min stand test were recorded, and skin vascular resistance, central hemodynamics, baroreflex sensitivity and heart rate variability were estimated. After DI we observed increased calf skin vascular resistance in the standing position (12.0 ± 1.0 AU-after- vs. 6.8 ± 1.4 AU-before), while supine it was unchanged. Cardiovascular deconditioning was confirmed by greater tachycardia on standing and by hypovolemia (-16 ± 3% at day 7 of DI). Total peripheral resistance and indices of cardiovascular autonomic control were not modified. In conclusion, unchanged autonomic control and total peripheral resistance suggest that increased skin vasoconstriction to standing involves rather local mechanisms-as venoarteriolar reflex-and might compensate insufficient vasoconstriction of other vascular beds.

Enforced physical inactivity increases endothelial microparticle levels in healthy volunteers.

A sedentary lifestyle has adverse effects on the cardiovascular system, including impaired endothelial functions. Subjecting healthy men to 7 days of dry immersion (DI) presented a unique opportunity to analyze the specific effects of enhanced inactivity on the endothelium. We investigated endothelial properties before, during, and after 7 days of DI involving eight subjects. Microcirculatory functions were assessed with laser Doppler in the skin of the calf. We studied basal blood flow and endothelium-dependent and -independent vasodilation. We also measured plasma levels of microparticles, a sign of cellular dysfunction, and soluble endothelial factors, reflecting the endothelial state. Basal flow and endothelium-dependent vasodilation were reduced by DI (22 + or - 4 vs. 15 + or - 2 arbitrary units and 29 + or - 6% vs. 12 + or - 6%, respectively, P < 0.05), and this was accompanied by an increase in circulating endothelial microparticles (EMPs), which was significant on day 3 (42 + or - 8 vs. 65 + or - 10 EMPs/microl, P < 0.05), whereas microparticles from other cell origins remained unchanged. Plasma soluble VEGF decreased significantly during DI, whereas VEGF receptor 1 and soluble CD62E were unchanged, indicating that the increase in EMPs was associated with a change in antiapoptotic tone rather than endothelial activation. Our study showed that extreme physical inactivity in humans induced by 7 days of DI causes microvascular impairment with a disturbance of endothelial functions, associated with a selective increase in EMPs. Microcirculatory endothelial dysfunction might contribute to cardiovascular deconditioning as well as to hypodynamia-associated pathologies. In conclusion, the endothelium should be the focus of special care in situations of acute limitation of physical activity.

Heart rate variability in preterm infants and maternal smoking during pregnancy.

OBJECTIVE: Tobacco smoke exposure increases the risk of premature birth and of dying of sudden infant death syndrome (SIDS). Prematurity significantly increases the risk of dying of SIDS, but mechanisms underlying this epidemiological finding are unclear. The cumulated effect of both prematurity and prenatal exposure to nicotine on autonomic heart rate control has not been studied. METHODS: Using coarse-graining spectral analysis, we compared heart rate variability (HRV) indices of preterm newborns at 33-34 weeks post-conceptional age from smoking (n = 19) and non-smoking (n = 21) mothers. Assessment of tobacco exposure relied on maternal reports and newborns cotinine analysis. We observed how indicators of HRV depended on gestational age at birth. RESULTS: At 33-34 weeks postconceptional age, the newborns from smoking mothers had lower HRV low frequency power normalised to the total spectral power (LF/TP) than the control group (median values: 8% vs. 15% respectively, p < 0.02). In the non-smoking group, RR-interval values and total HRV power were correlated with gestational age at birth, with a shorter RR and a lower total HRV power in lesser gestational ages (rho = 0.67, p = 0.03, rho = 0.71, p = 0.003 respectively). This correlation was not observed for RR values in the group with smoking mothers.