A theory-derived index of consciousness, which quantifies the complexity of the brain’s response to a stimulus, measures the level of consciousness in awake, sleeping, anesthetized, and brain-damaged subjects.

No abstract

Cardiac pacemaking generation and modulation rely on the coordinated activity of several processes. Although a wealth of evidence indicates a relevant role of the I f ("funny," or pacemaker) current, whose molecular constituents are the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels and particularly HCN4, work with mice where Hcn genes were knocked out, or functionally modified, has challenged this view. However, no previous studies used a cardiac-specific promoter to induce HCN4 ablation in adult mice. We report here that, in an inducible and cardiac-specific HCN4 knockout (ciHCN4-KO) mouse model, ablation of HCN4 consistently leads to progressive development of severe bradycardia (∼50% reduction of original rate) and AV block, eventually leading to heart arrest and death in about 5 d. In vitro analysis of sinoatrial node (SAN) myocytes isolated from ciHCN4-KO mice at the mean time of death revealed a strong reduction of both the I f current (by ∼70%) and of the spontaneous rate (by ∼60%). In agreement with functional results, immunofluorescence and Western blot analysis showed reduced expression of HCN4 protein in SAN tissue and cells. In ciHCN4-KO animals, the residual I f was normally sensitive to β-adrenergic receptor (β-AR) modulation, and the permanence of rate response to β-AR stimulation was observed both in vivo and in vitro. Our data show that cardiac HCN4 channels are essential for normal heart impulse generation and conduction in adult mice and support the notion that dysfunctional HCN4 channels can be a direct cause of rhythm disorders. This work contributes to identifying the molecular mechanism responsible for cardiac pacemaking.funny current | heart rate | sinoatrial node | atrioventricular node | chronotropism T he degree of complexity of the processes involved in pacemaking and their individual contributions is still a hotly debated issue (1, 2). Despite this complexity, and granting the fact that perturbation of any participating mechanism can affect rate, there is evidence for a functional specificity of "funny" (f)-channels in mediating generation and physiological control of pacemaker activity.Native f-channels are encoded by four hyperpolarizationactivated, cyclic nucleotide-gated channel genes (Hcn1-4), of which Hcn4 is by far the most highly expressed in the cardiac pacemaker regions of different species (3-6). HCN4 contributes 80% of total HCN mRNA in rabbit and mouse sinoatrial node (SAN), the remaining 20% being a combination of HCN2 and HCN1, with species-dependent relative abundance (4,5,(7)(8)(9). Evidence for the role of f/HCN4 channels in pacemaking relies on several experimental data (10):i) The "funny" (I f ) current and pacemaker activity are correlated; i.e., functional expression of f-channels is restricted to pacemaking regions [SAN, atrioventricular node (AVN), and the ventricular conduction system], demonstrating a commitment to regulation of pacemaker activity. This correlation exists not only in the adult but also throughout development, such that ...

We exploit time reversibility analysis, checking the invariance of statistical features of a series after time reversal, to detect temporal asymmetries of short-term heart period variability series. Reversibility indexes were extracted from 22 healthy fetuses between 16th to 40th wk of gestation and from 17 healthy humans (aged 21 to 54, median ϭ 28) during graded head-up tilt with table inclination angles randomly selected inside the set {15, 30, 45, 60, 75, 90}. Irreversibility analysis showed that nonlinear dynamics observed in short-term heart period variability are mostly due to asymmetric patterns characterized by bradycardic runs shorter than tachycardic ones. These temporal asymmetries were 1) more likely over short temporal scales than over longer, dominant ones; 2) more frequent during the late period of pregnancy (from 25th to 40th week of gestation); 3) significantly present in healthy humans at rest in supine position; 4) more numerous during 75 and 90°head-up tilt. Results suggest that asymmetric patterns observable in short-term heart period variability might be the result of a fully developed autonomic regulation and that an important shift of the sympathovagal balance toward sympathetic predominance (and vagal withdrawal) can increase their presence. heart rate variability; autonomic nervous system; head-up tilt; fetal maturation; nonlinear dynamics THE VARIABILITY OF HEART PERIOD (usually approximated as the temporal distance between two consecutive R peaks on the ECG, R-R) has been proven to be nonlinear in healthy fetuses between 38th and 40th week of gestation (8) and in healthy humans (1, 4), mostly during experimental conditions periodically forcing cardiovascular regulation (i.e., controlled breathing) (15, 16). However, this finding has not been translated yet into a notion actually helpful in pathophysiology. The main reason is that, until now, the detection of nonlinear dynamics has not been linked to a clear temporal correlate (i.e., a pattern associated with nonlinear dynamics).Time irreversibility analysis checks the invariance of the statistical properties of a time series after time reversal. This analysis might be helpful to translate the involved concept of nonlinear dynamics into a simple, comprehensible notion useful in pathophysiology, since it clearly indicates a time domain scheme responsible for nonlinear dynamics. Indeed, time irreversibility analysis is capable of detecting a specific class of nonlinear dynamics, that is, those characterized by a temporal asymmetry. In other words, when a series is detected as irreversible using simple tests in the two-dimensional phase space (6, 9, 17), it can be stated that the nonlinear behavior is the result of the presence of asymmetric patterns (i.e., waveforms characterized by the upward side shorter or longer than the downward side), thus directly linking the abstract concept of nonlinear dynamics to a clear, easily imaginable, feature (17).The aim of this study is twofold. The first aim is to link the presence of temporal asymme...

Sleep is a physiological process involving different biological systems, from molecular to organ level; its integrity is essential for maintaining health and homeostasis in human beings. Although in the past sleep has been considered a state of quiet, experimental and clinical evidences suggest a noteworthy activation of different biological systems during sleep. A key role is played by the autonomic nervous system (ANS), whose modulation regulates cardiovascular functions during sleep onset and different sleep stages. Therefore, an interest on the evaluation of autonomic cardiovascular control in health and disease is growing by means of linear and non-linear heart rate variability (HRV) analyses. The application of classical tools for ANS analysis, such as HRV during physiological sleep, showed that the rapid eye movement (REM) stage is characterized by a likely sympathetic predominance associated with a vagal withdrawal, while the opposite trend is observed during non-REM sleep. More recently, the use of non-linear tools, such as entropy-derived indices, have provided new insight on the cardiac autonomic regulation, revealing for instance changes in the cardiovascular complexity during REM sleep, supporting the hypothesis of a reduced capability of the cardiovascular system to deal with stress challenges. Interestingly, different HRV tools have been applied to characterize autonomic cardiac control in different pathological conditions, from neurological sleep disorders to sleep disordered breathing (SDB). In summary, linear and non-linear analysis of HRV are reliable approaches to assess changes of autonomic cardiac modulation during sleep both in health and diseases. The use of these tools could provide important information of clinical and prognostic relevance.

IMT demonstrates beneficial effects on systolic and diastolic blood pressure as well as autonomic cardiovascular control in hypertensive patients.

RV dysfunction is associated with reduced systemic parasympathetic activity in patients with PAH, with an inadequate adaptive response of the cholinergic system in the RV. Enhancing parasympathetic activity by PYR improved survival, RV function, and pulmonary vascular remodeling in experimental PH.

ObjectivesSince ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects.Design76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68±6 years, 34% males, body mass index 25±3 kg/m2). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months.ResultsSubjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PEmax (34%, p<0.0001) and PImax (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group.ConclusionRespiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance.Trial RegistrationCinicalTrials.gov identifier: NCT00969345; trial registry name: Effects of respiratory yoga training (Bhastrika) on heart rate variability and baroreflex, and quality of life of healthy elderly subjects.