Effect of anxiety on the function of the cardiorespiratory system

The effects of anxiety on the external respiration system and respiratory sinus arrhythmia (RSA) were studied in healthy subjects in real-life conditions. Changes in external respiration parameters and heart rate variability (HRV) in students going to take their end-of-term exams were assessed relative to a midterm period, and the cardiorespiratory system was monitored in a longitudinal study for 50 days. The function of the cardiorespiratory system was characterized by measuring external respiration parameters and calculating HRV parameters. State anxiety (SA) was assessed using Spielberger’s scale. An increase in SA before an exam was accompanied by a higher breathing rate, a higher tidal volume, and lower HRV indices, especially those related to respiratory sinus arrhythmia (HF and HF _norm). The changes in the parameters depended on the increase in SA. A negative correlation was observed between midterm HF and pre-exam SA. The longitudinal study revealed a distinct negative correlation between respiratory sinus arrhythmia parameters and peak expiratory flow (PEF) and a positive correlation between SA and PEF in the majority of subjects. Changes in cardiorespiratory parameters depended on the changes in SA in the longitudinal study. An increase in SA was accompanied by substantial changes in respiratory sinus arrhythmia (RAS) and external respiration parameters, and their correlation was assumed to indicate that modification of parasympathetic activity plays a leading role in increasing PEF.     

Breath-by-breath analysis of cardiorespiratory interaction for quantifying developmental maturity in premature infants

In healthy neonates, connections between the heart and lungs through brain stem chemosensory pathways and the autonomic nervous system result in cardiorespiratory synchronization. This interdependence between cardiac and respiratory dynamics can be difficult to measure because of intermittent signal quality in intensive care settings and variability of heart and breathing rates. We employed a phase-based measure suggested by Sch?fer and coworkers (Sch?fer C, Rosenblum MG, Kurths J, Abel HH. Nature 392: 239-240, 1998) to obtain a breath-by-breath analysis of cardiorespiratory interaction. This measure of cardiorespiratory interaction does not distinguish between cardiac control of respiration associated with cardioventilatory coupling and respiratory influences on the heart rate associated with respiratory sinus arrhythmia. We calculated, in sliding 4-min windows, the probability density of heartbeats as a function of the concurrent phase of the respiratory cycle. Probability density functions whose Shannon entropy had a <0.1% chance of occurring from random numbers were classified as exhibiting interaction. In this way, we analyzed 18 infant-years of data from 1,202 patients in the Neonatal Intensive Care Unit at University of Virginia. We found evidence of interaction in 3.3 patient-years of data (18%). Cardiorespiratory interaction increased several-fold with postnatal development, but, surprisingly, the rate of increase was not affected by gestational age at birth. We find evidence for moderate correspondence between this measure of cardiorespiratory interaction and cardioventilatory coupling and no evidence for respiratory sinus arrhythmia, leading to the need for further investigation of the underlying mechanism. Such continuous measures of physiological interaction may serve to gauge developmental maturity in neonatal intensive care patients and prove useful in decisions about incipient illness and about hospital discharge.     

Associations of Sedentary Behaviour,Physical Activity,Blood Pressure and Anthropometric Measures with Cardiorespiratory Fitness in Children with Cerebral Palsy

Background

Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk.

Purpose

The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP.

Methods

This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated.

Results

Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r² = -0.451, p<0.01), waist circumference (r² = -0.560, p<0.001), waist-height ratio (r² = -0.560, p<0.001) and systolic blood pressure (r² = -0.306, p<0.05) after adjustment for age, sex and GMFCS level.

Conclusions

Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk.     

Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia

Hyperpolarization-activated cyclic nucleotide-gated channel 4 gene HCN4 is a pacemaker channel that plays a key role in automaticity of sinus node in the heart, and an HCN4 mutation was reported in a patient with sinus node dysfunction. Expression of HCN4 in the heart is, however, not confined to the sinus node cells but is found in other tissues, including cells of the conduction system. On the other hand, mutations in another cardiac ion channel gene, SCN5A, also cause sinus node dysfunction as well as other cardiac arrhythmias, including long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, and progressive cardiac conduction disturbance. These observations imply that HCN4 abnormalities may be involved in the pathogenesis of various arrhythmias, similar to the SCN5A mutations. In this study, we analyzed patients suffering from sinus node dysfunction, progressive cardiac conduction disease, and idiopathic ventricular fibrillation for mutations in HCN4. A missense mutation, D553N, was found in a patient with sinus node dysfunction who showed recurrent syncope, QT prolongation in electrocardiogram, and polymorphic ventricular tachycardia, torsade de pointes. In vitro functional study of the D553N mutation showed a reduced membranous expression associated with decreased If currents because of a trafficking defect of the HCN4 channel in a dominant-negative manner. These data suggest that the loss of function of HCN4 is associated with sinus nodal dysfunction and that a consequence of pacemaker channel abnormality might underlie clinical features of QT prolongation and polymorphic ventricular tachycardia developed under certain conditions.     

Effect of Ibutilide on the Canine Cardiac Conduction System

The objective of the study was to evaluate the effect of ibutilide on canine cardiac sinoatrial and atrioventricular nodes (AVNs). For this purpose, 18 mongrel dogs were injected intravenously with ibutilide and the changes in heart rate, sinus node recovery time, and AVN were measured. Our data show that ibutilide administration caused significant suppression of the sinus atrial node, the peak response time was 20?C30?min, and the heart rate was restored to pre-drug administration level. After receiving ibutilide, 1 animal had a 5?s sinus pause, and after 5?min of ibutilide administration, 1 dog showed 2:1 atrioventricular conduction. Therefore, it was concluded that ibutilide had a suppressive effect on the sinoatrial node and AVN.     

The use of spiroarteriocardiorhythmography as a functional test for estimating the state of the cardiorespiratory system in adults and children

The heart rate, peripheral arterial blood pressure (BP), and respiration parameters were simultaneously recorded in adult subjects and young schoolchildren in two modes of testing: using a mask with airflow sensors that did not restrict air inflow but increased the pulmonary dead space and without the mask. It was demonstrated that wearing the mask was a functional test for the state of the cardiorespiratory system in both age groups; however, the responses of the children’s and adults’ bodies differed from each other, probably, because of the functional immaturity of the sympathetic component of the autonomic control. In adults, the parameters of the cardiovascular system did not change, except that the heart rate variability spectrum was redistributed toward an enhancement of the high-frequency component. In children, testing with the mask on decreased the systolic BP; increased the heart rate; and, as evidenced by the spectral characteristics of BP variability, activated the sympathetic nervous system.     

Long-term effects of graduated compression stockings on cardiorespiratory performance

The use of graduated compression stockings (GCS) in sport has been increasing in the last years due to their potential positive effects for athletes. However, there is little evidence to support whether these types of garments actually improve cardiorespiratory performance. The aim of this study was to examine the cardiorespiratory responses of GCS during running after three weeks of regular use. Twenty recreational runners performed three tests on different days: test 1) – a 5-min maximal effort run in order to determine the participants’ maximal aerobic speed; and tests 2) and 3) – a fatigue running test of 30 minutes at 80% of their maximal aerobic speed with either GCS or PLACEBO stockings at random. Cardiorespiratory parameters (minute ventilation, heart rate, relative oxygen consumption, relative carbon dioxide production, ventilatory equivalents for oxygen and carbon dioxide, and oxygen pulse) were measured. Before each test in the laboratory, the participants trained with the randomly assigned stockings (GCS or PLACEBO) for three weeks. No significant differences between GCS and PLACEBO were found in any of the cardiorespiratory parameters. In conclusion, the present study provides evidence that running with GCS for three weeks does not influence cardiorespiratory parameters in recreational runners.     

Heart Rate Variability Biofeedback Improves Cardiorespiratory Resting Function During Sleep

The present study was designed to examine the effect of heart rate variability (HRV) biofeedback on the cardiorespiratory resting function during sleep in daily life. Forty-five healthy young adults were randomly assigned to one of three groups: HRV biofeedback, Autogenic Training (AT), and no-treatment control. Participants in the HRV biofeedback were instructed to use a handheld HRV biofeedback device before their habitual bedtime, those in the AT were asked to listen to an audiotaped instruction before bedtime, and those in the control were asked to engage in their habitual activity before bedtime. Pulse wave signal during sleep at their own residences was measured continuously with a wristwatch-type transdermal photoelectric sensor for three time points. Baseline data were collected on the first night of measurements, followed by two successive nights for HRV biofeedback, AT, or control. Cardiorespiratory resting function was assessed quantitatively as the amplitude of high-frequency (HF) component of pulse rate variability, a surrogate measure of respiratory sinus arrhythmia. HF component increased during sleep in the HRV biofeedback group, although it remained unchanged in the AT and control groups. These results suggest that HRV biofeedback before sleep may improve cardiorespiratory resting function during sleep.     

Respiratory sinus arrhythmia in freely moving and anesthetized rats.

Heart rate increases during inspiration and slows during postinspiration; this respiratory sinus arrhythmia helps match pulmonary blood flow to lung inflation and maintain an appropriate diffusion gradient of oxygen in the lungs. This cardiorespiratory pattern is found in neonatal and adult humans, baboons, dogs, rabbits, and seals. Respiratory sinus arrhythmia occurs mainly due to inhibition of cardioinhibitory parasympathetic cardiac vagal neurons during inspiration. Surprisingly, however, a recent study in anesthetized rats paradoxically found an enhancement of cardiac vagal activity during inspiration, suggesting that rats have an inverted respiratory sinus arrhythmia (Rentero N, Cividjian A, Trevaks D, Pequignot JM, Quintin L, and McAllen RM. Am J Physiol Regul Integr Comp Physiol 283: R1327-R1334, 2002). To address this controversy, this study examined respiratory sinus arrhythmia in conscious freely moving rats and tested whether the commonly used experimental anesthetics urethane, pentobarbital sodium, or ketamine-xylazine alter respiratory sinus arrhythmia. Heart rate significantly increased 21 beats/min during inspiration in conscious rats, a pattern similar to the respiratory sinus arrhythmia that occurs in other species. However, anesthetics altered normal respiratory sinus arrhythmia. Ketamine-xylazine (87 mg/kg and 13 mg/kg) depressed and pentobarbital sodium (60 mg/kg) abolished normal respiratory sinus arrhythmia. Urethane (1 g/kg) inverted the cardiorespiratory pattern so that heart rate significantly decreased during inspiration. Our study demonstrates that heart rate normally increases during inspiration in conscious, freely moving rats, similar to the respiratory sinus arrhythmia pattern that occurs in other species but that this pattern is disrupted in the presence of general anesthetics, including inversion in the case of urethane. The presence and consequences of anesthetics need to be considered in studying the parasympathetic control of heart rate.     

Features of cardio-respiratory synchronization phenomenon in children with different types of the nervous system

Human breathing and cardiac rhythms become synchronized during voluntary respiration of a subject with the rate higher than the initial cardiac rate. This phenomenon is observed during driving of the breathing rhythm with rhythmical flashes of a photostimulator lamp. The broadest bandwidth of the range of cardiorespiratory synchronization was observed in phlegmatic children, and the narrowest bandwidth was observed in choleric children. The dependence of characteristics of combined heart and breathing rhythmogenesis on temperamental types is determined by the properties of the nervous system, i.e., force, balance, and flexibility.     

Atrial fibrillation precipitated by acute hypovolaemia.

Six patients with varying degrees of acute cardiorespiratory failure were seen. All patients deteriorated noticeably when rapid atrial fibrillation developed. In all patients intravenous digitalis failed to slow the ventricular response, and in three patients misguided attempts at electrical cardioversion failed. Haemodynamic monitoring showed a normal or low pulmonary artery occlusion pressure in all patients. Controlled expansion of plasma volume was associated with an immediate slowing of the heart rate in all patients, and the heart rate in all patients returned to sinus rhythm within 30 minutes of transfusion. It is suggested that hypovolaemia in critically ill patients may contribute to the development of atrial fibrillation.     

Ultrastructural study of specialized conducting and working myocytes in the sinoatrial region of the human heart. I. Qualitative analysis

A qualitative ultrastructural analysis of specialized conducting and working myocytes in the sinoatrial region of the human heart was made using autopsied and biopsied material from 45 men and women. Autopsied material was prepared not later as than 3 hours after the death. Biopsied material was taken during the operation for surgical correction of disturbances of cardiac rhythm and conduction. Cell contacts of light and dark myocytes within the sinus node, and of working myocytes of the right atrium were evaluated. The ratio of light to dark myocytes in the sinus node were estimated from both dead people and patients. The principles of correct ultrastructural classification of conducting and working myocytes in human heart are discussed.     

Sinus rhythm: mechanisms and function

The normal cardiac rhythm originates in a specialized region of the heart, the sinus node that is part of the nodal tissue. The rhythmic, impulse initiation of sinus node pacemaker cells results from a spontaneous diastolic depolarization that is initiated immediately after repolarization of the preceding actions potential. This slow diastolic depolarisation is typical of automatic cells and essential to their function. Several currents are involved in this diastolic depolarisation: a hyperpolarization activated inward current, termed "pacemaker" I(f) current, two Ca2+ currents (a L type and a T type), a delayed K+ current and a Na/Ca exchange current. The frequency of the automatic discharge is the main determinant of heart rate. However the sinus node activity is regulated by adrenergic and cholinergic neurotransmitters. Acetylcholine provokes the hyperpolarization of pacemaker cells and decreases the speed of the spontaneous diastolic depolarisation, thus slowing the sinus rate. Catecholamines lead to sinus tachycardia by increasing the diastolic depolarisation speed. In normal conditions, the observed resting heart rate is lower than the intrinsic frequency of the sinus node due to a "predominance" of the vagal tone. Neural regulation of the heart rate aims at meeting the metabolic needs of the tissues through a varying blood flow. Differences between diurnal and nocturnal mean heart rates are accounted for by neural influences. During the night, the increased vagal tone results in decreased heart rate. The exercise-induced tachycardia results from the sympathetic stimulation. It allows more blood to reach skeletal muscles, and as a consequence an increased supply of oxygen and nutrients. Compared to the variety of clinical arrhythmias, sinus rhythm is the basis for optimal exercise capacity and quality of life.     

Oscillations of heart rate and respiration synchronize during poetry recitation

The objective of this study was to investigate the synchronization between low-frequency breathing patterns and respiratory sinus arrhythmia (RSA) of heart rate during guided recitation of poetry, i.e., recitation of hexameter verse from ancient Greek literature performed in a therapeutic setting. Twenty healthy volunteers performed three different types of exercises with respect to a cross-sectional comparison: 1). recitation of hexameter verse, 2). controlled breathing, and 3). spontaneous breathing. Each exercise was divided into three successive measurements: a 15-min baseline measurement (S1), 20 min of exercise, and a 15-min effect measurement (S2). Breathing patterns and RSA were derived from respiratory traces and electrocardiograms, respectively, which were recorded simultaneously using an ambulatory device. The synchronization was then quantified by the index gamma, which has been adopted from the analysis of weakly coupled chaotic oscillators. During recitation of hexameter verse, gamma was high, indicating prominent cardiorespiratory synchronization. The controlled breathing exercise showed cardiorespiratory synchronization to a lesser extent and all resting periods (S1 and S2) had even fewer cardiorespiratory synchronization. During spontaneous breathing, cardiorespiratory synchronization was minimal and hardly observable. The results were largely determined by the extent of a low-frequency component in the breathing oscillations that emerged from the design of hexameter recitation. In conclusion, recitation of hexameter verse exerts a strong influence on RSA by a prominent low-frequency component in the breathing pattern, generating a strong cardiorespiratory synchronization.     

The effect of sinus node depression on heart rate variability in humans using zatebradine, a selective bradycardic agent

Zatebradine is a bradycardic agent with a selective effect on the pacemaker current in the sinus node. The effect of such drugs on heart rate variability is not known. Thirty-six patients without structural heart disease were randomly assigned to receive 10 mg of zatebradine i.v. (n = 24) or isotonic saline (n = 12). Heart rate variability (HRV) was recorded as power in the very low frequency (VLF, 0.003-0.040 Hz), low frequency (LF, 0.040-0.150 Hz), and high frequency (HF, 0.150-0.400 Hz) spectral bands as well as total power (TP, 0.003-0.400 Hz) during 5-min ECG acquisitions at baseline, 30, and 60 min following the start of the infusion. No change in heart rate variability was detected in the control group. Zatebradine significantly reduced heart rate variability at 60 min in all frequency bands: VLF (-12+/-4%, p<0.001), LF (-19+/-4%, p<0.001), and HF (-26+/-5%, p<0.001). The reduction in HRV following zatebradine is due to depression of sinus node response to all external stimuli and underscores the need for documentation of normal sinus node function in HRV research.     

Sinus Node Dysfunction as the First Manifestation of Left Ventricular Noncompaction with Multiple Cardiac Abnormalities

Left ventricular noncompaction (LVNC) is a genetically heterogenous form of cardiomyopathy which may remain undiagnosed till adulthood due to the late presentation of typical symptoms such as dyspnea, congestion, ventricular arrhythmias and thromboembolism. Symptomatic bradycardia secondary to persistent sinus node dysfunction is very rare. Coexistent cardiac defects are common in children however in adults the disease is usually in isolated form. Here, we present a case of twenty-three year-old female LVNC patient with patent ductus arteriosus, bicuspid aortic valve and persistent sinus node dysfunction who presented with dizziness as the first manifestation of the disease.     

Power spectral and Poincaré plot characteristics in sinus node dysfunction.

A salient feature of the normal sinus node activity is its prominent beat-to-beat variability, which shows self-similarity on different time scales (fractal dynamics). However, in patients with sinus node dysfunction, short-term time sinus cycles show exaggerated variability, the characteristics of which have not been analyzed. Therefore, Poincaré plots and power spectral analysis were applied to short-term variations of sinus cycles in 30 patients with and 30 patients without sinus node disease. Three patterns of behavior were observed in sick sinus patients: type 1, completely normal (n = 3); type 2, randomlike pattern in the Poincaré plots with "white noise" power spectra (n = 9); and type 3, a transitional pattern, characterized by remnants of normal behavior mixed with scattered points (n = 18). In control subjects, only type 1 (n = 27) and type 3 (n = 3) patterns were observed, P < 0.0001. The power spectral changes in sinus node dysfunction are thus characterized by a loss of the inverse power law relationship, which both has implications for heart rate variability analysis and might offer a new diagnostic approach.     

Management of paroxysmal ectopic atrial tachycardia with long sinus pauses in a teenager

Sinus pauses in the setting of supraventricular tachycardia is rare in children. We describe an asymptomatic teen with irregular heart rate detected during an incidental exam who was found to have short runs of a slow ectopic atrial tachycardia on electrocardiogram and prolonged sinus pauses on routine ambulatory ECG. Successful catheter ablation of the ectopic atrial tachycardia led to resolution of the sinus pauses.     

Effects of Regulatory Peptides on Electrophysiological Properties of the Human Heart

During transesophageal electrical stimulation of the left atria in patients with heart diseases, an intravenous administration of Sandostatin prolonged the cardiac cycle and the effective refractory period of the atrioventricular junction, slowed down the sinoatrial conduction and the sinus node recovery time, and shifted the Wenckebach's point downwards. Neurotensin produced effects opposite to those of Sandostatin. During the Valsalva maneuver, Sandostatin strengthened bradycardia and broadened the range of heart rate changes associated with the vagal tone variations. The latter effect was also observed after the administration of neurotensin. Met-enkephalin and dalargin shortened the cardiac cycle, increased the corrected time of sinus node recovery time, but did not affect the cardiac rhythm dynamics during the Valsalva maneuver. These findings suggest that the regulatory peptides can be involved in control mechanisms determining the electrophysiological parameters of the human heart.     

Optical mapping of activation patterns in an animal model of congenital heart block

Congenital heart block (CHB) is associated with high mortality and affects children of mothers with autoantibodies (IgG) to ribonucleoproteins SSB/La and SSA/Ro. IgG from mothers of children with CHB (positive IgG) was used to assess activation patterns in both the right atrium (RA) and right ventricle (RV) of Langendorff-perfused young rabbit hearts. Optical action potentials (AP) were obtained by using a 124-site photodiode array with 4-[-[2-(di-n-butylamino)-6-naphthyl]vinyl]pyridinium. Optical APs were recorded to simultaneously image activation patterns from the RA and RV. Perfusion of positive IgG (800--1,200 micro resulted in sinus bradycardia and varying degrees of heart block. Activation maps revealed marked conduction delay at the sinoatrial junction but only minor changes in overall atrial and ventricular activation patterns. No conduction disturbances were seen in the presence of IgG from mothers with healthy children. In conclusion, besides atrioventricular (AV) block, positive IgG induces sinus bradycardia. These results establish that the sequelae of CHB are associated with impaired intrasinus and/or sinoatrial conduction. The findings raise the possibility that sinus bradycardia in the developing heart may indicate the potential for AV conduction disturbances.