Regulation Of Cardiac Rhythm Research Articles

Polytherapy with hERG‐blocking antiepileptic drugs: Increased risk for embryonic cardiac arrhythmia and teratogenicity

The antiepileptic drugs (AEDs) phenytoin, phenobarbital, dimethadione, and carbamazepine cause a similar pattern of malformations in humans, with an increased risk after polytherapy. The teratogenicity has been linked to cardiac rhythm disturbances and hypoxic damage as a consequence of their common potential to inhibit a specific potassium ion current (IKr). The IKr is of major importance for embryonic cardiac repolarization and rhythm regulation. This study investigated whether these AEDs cause irregular rhythm and if various combinations of AEDs result in higher arrhythmia risk than exposure to a single AED. The effects on heart rhythm of a single AED (monotherapy), and of various combinations (polytherapy) of AEDs, in gestational day 10 C57BL mouse embryos in culture were analyzed and graphically illustrated during a 25 s recording with a digitalization technique. All of the studied AEDs caused increased intervals between heartbeats (resulting in bradycardia) and large variations in the interval between heartbeats (resulting in irregular rhythm) in a concentration-dependent manner in cultured mouse embryos. Dimethadione caused irregular rhythm at concentrations within and phenytoin slightly above the therapeutic ranges. Polytherapy resulted in more substantial prolongation of the mean interval between heartbeats (>60 ms) than monotherapy at clinically relevant concentrations. The results suggest that polytherapy more than monotherapy causes substantial prolongation of the cardiac repolarization, a marker associated with high risk of developing irregular rhythm during longer exposure periods (days to months). This supports the idea that the increased risk for malformations following polytherapy is linked to an increased risk for cardiac rhythm disturbances.

Significance of cardiac cannabinoid receptors in regulation of cardiac rhythm, myocardial contractility, and electrophysiologic processes in heart

Intravenous administration of cannabinoid (CB) receptor agonists (HU-210, 0.1 mg/kg; ACPA, 0.125 mg/kg; methanandamide, 2.5 mg/kg; and anandamide, 2.5 mg/kg) induced bradycardia in chloralose-anesthetized rats irrespective of the solubilization method. Methanandamide, HU-210, and ACPA had no effect on the electrophysiological activity in the heart, while anandamide increased the duration of the QRS complex. The negative chronotropic effect of HU-210 was due to CB1 receptor activation since is was not observed after CB1 receptor blockade by SR141716A (1 mg/kg intravenously) but was present after pretreatment with CB2 receptor antagonist SR144528 (1 mg/kg intravenously). CB receptor antagonists SR141716A and SR144528 had no effect on cardiac rhythm or ECG indices. Hence, in the intact heart, endogenous CB receptor agonists are not involved in the regulation of cardiac rhythm and electrophysiological processes. The chronotropic effect of CBs was independent of the autonomic nervous system because it remained significant after autonomic ganglion blockade by hexamethonium (1 mg/kg intravenously). CB receptor activation by HU-210 (0.1 and 1 microM) in vitro decreased the rate and force of isolated heart contractions, the rates of contraction and relaxation, and end diastolic pressure. The negative chronotropic effect of HU-210 was less pronounced in vitro than in vivo. The maximum inotropic effect of HU-210 was reached at the concentration of 0.1 microM.

Autonomic homeostasis and the specific features of adaptation in children with obesity

The autonomic nervous system and the adaptive mechanisms associated with neuroautonomic cardiac rhythm regulation were studied in obese children. The study covered 187 untreated children aged 6-16 years who had exogenous constitutional (n = 68), diencephalic (n = 20) obesity and hypothalamic puberty syndrome (n = 99). The study was conducted by computer-aided (statistic, spectral) analysis of cardiac rhythm variability. The regulatory system activity index was calculated to assess the tension of adaptive mechanisms. The results were compared with those obtained in 107 apparently healthy children matched by gender and age. The enhanced activity of subcortical nerve centers with a predominance of sympathetic effects was observed in 38.7% of children with puberty obesity. The state of adaptive processes was regarded as a pronounced functional strain, overstrain, and exhaustion of regulatory systems in 31.1% of 6-10-year-old children and 29.5% of 11-16-year-old ones with obesity.

Reactions of the autonomic nervous system of students with different characteristics of higher nervous activity in the situation of examination stress

The influence of examination stress on the reactions of the autonomic nervous system in students with different levels of functional mobility of nervous processes (FMNP) was studied. More intense functioning of the cardiovascular system and the strain of all regulatory mechanisms during examination stress were characteristic of individuals with low FMNP, whereas students with high FMNP values were characterized by a weaker strain of the mechanisms of cardiac rhythm regulation, more economical activity of the cardiovascular system, and better performance on the examinations. The activation of humoral, metabolic, and sympathetic effects was observed in all the subjects under examination stress, along with decreased parasympathetic effects on the cardiac rhythm.

Regulation of sinus cardiac rhythm during different states of attention in full-term and preterm 5-month-old infants

Parasympathetic heart rate regulation was studied in full-term (FT) and very preterm (VPT) infants at the corrected age of 5 months during endogenous and exogenous sustained attention. Cardiac interval duration and the respiratory sinus arrhythmia (RSA) were used as indices of parasympathetic regulation of heart activity during infants’ sustained attention to a new visual stimulus (exogenous attention) and anticipatory attention to repeatedly appearing and disappearing stimuli in the visual expectation paradigm (endogenous attention). The psychomotor development and behavior regulation were assessed using the Bayley Scales of Infant Development, and the clinical risk was scored on the Ballard scale. A shift of attention state affected the RSA only in the FT infants. The endogenous attention was associated with a relatively high RSA level, with the higher RSA levels being significantly correlated with the Bayley Behavior Rating Scale scores. At the age of 5 months, the degree of clinical risk in the VPT infants was not correlated with specific features of parasympathetic regulation. The results are discussed in terms of the concepts of physiological mechanisms of exogenous and endogenous attention in infants. The central regulation of the autonomic functions during a shift of attention state is less efficient in healthy VPT infants as compared to their FT peers. The RSA reactivity can be a more sensitive indicator of CNS regulatory disorders than the standard indices of clinical risk.

Association of betaxolol therapy with the clinical and functional parameters in patients with essential hypertension

The association of clinical and functional parameters was studied in patients with mild and moderate arterial hypertension (All) during therapy with betaxolol (Lokren), Twenty six patients (19 males and 7 females) aged 28 to 56 (mean 40.5 ± 1.4) years who had grade 1-2 AH were examined. The patients received monotherapy with betaxolol in a single dose of 10 mg/day. 24-hour ECG and blood pressure monitoring, stress-echocardiography during the arithmetic test estimating cognitive functions and life quality by the SP-36 scale were performed at the baseline and following 8 weeks of therapy. It has been found that betaxolol (Lokren) used In a single dose of 10 mg/day for 8 weeks has a high antihypertensive efficacy, stabilizes the autonomic balance of cardiac rhythm regulation, by simultaneously showing antiarrhythmic properties, reduces the degree of stress responsiveness, and enhances the inhibition of the central nervous system, by ultimately improving the quality of life in the patients.

Arterial hypertension in patients with chronic bronchopulmonary diseases: The heart as a target organ is the focus of the problem

Fifty-seven patients with grade 1 essential hypertension concurrent with chronic obstructive bronchitis or bronchial asthma were examined. They were found to have characteristics of the daily blood pressure profile, such as a high load due to pressure and its inadequate nocturnal lowering. The concentric type of left ventricular hypertrophy (LVH) is typical of the vast majority of persons of this category. The patients with a high LVH concentricity have more significant imbalance of autonomic cardiac rhythm regulation with the preponderance of myocardial sympathetic impact while those with low LVH concentricity showed higher aldosterone secretion.

Is erythromycin therapy teratogenic in humans?

The possible teratogenic effect of erythromycin therapy, noted previously, was studied. Women who had taken erythromycin or penicillin V in early pregnancy and their infants were studied, using the Swedish Medical Birth Register where information on drug use during pregnancy was recorded based on interviews in early pregnancy. The risk for any congenital malformation after erythromycin therapy (but not after penicillin V therapy) was increased (odds ratio 1.24, 95% confidence interval: 1.01–1.51) and this was due to an effect on cardiovascular malformations (odds ratio 1.92, 95% CI: 1.37–2.68). There was also an indicated increased risk for pyloric stenosis (risk ratio 3.0, 95% CI: 1.1–8.5 after exposure in early pregnancy). Various explanations to the finding are discussed, one of them linked to the fact that erythromycin inhibits a specific cardiac potassium channel (IKr) which seems to play a major role in cardiac rhythm regulation in the early embryo. Potent blocking drugs cause as a class effect cardiac defects in animal experiments.

Autonomic cardiac rhythm regulation and the parameters of signal-averaged ECG in patients with hypertensive disease

The study was undertaken to evaluate autonomic cardiac rhythm regulation in patients with hypertensive disease (HD) in the presence and absence of late ventricular potentials (LVPs) Eighty five hypertensive patients aged 30 to 73 years (mean age 54±9 years) were examined In all the patients, LVPs were recorded by signal-averaged ECG and cardiac rhythm variability was analyzed This study revealed that in a group of HD patients with detected LVPs, cardiac rhythm variability was less than that in those without LVPs The HD patients with detected LVPs showed an increase in their sympathetic impact on cardiac rhythm regulation, as manifested by significantly higher LF/HF ratios (1,85±0,21 and 1,15±0,15, respectively,p<0,05) than did the patients without LVPs This is also confirmed by a moderate positive correlation between LF/HF and TotalQRS r=0,43,p=0,0001

Role of sympathetic and parasympathetic mechanisms in formation of secondary cardiac rhythms in rats ontogenesis

In progeny of Wistar rats aged from birth to 3 week, there was studied participation of sympathetic and parasympathetic mechanisms in regulation of cardiac rhythm and its rhythmic oscillations (secondary cardiac rhythms), whose spectral composition was analyzed using rapid Fourier transformation. Consequences, which changed in the process of development, of blockade of β-adrenoreceptors by propranolol, of α-adrenoreceptors by phentolamine, and of muscarinic cholinoreceptors by atropine as well as of chronic desympathization by guanethidine (isobarine). It was found that due to heterochronia in establishment of functions of sympathetic and parasympathetic nervous systems, reactions to blockade of adreno- and cholinoreceptors for the first 3 weeks of postnatal ontogenesis changed not only quantitatively, but also qualitatively. Blockade of adrenoreceptors in newborn animals leads to an increase of power of the rhythm oscillations in all low-frequency diapasons. The baroreflex function of parasympathetic innervation is well expressed as early as in newborns. Tonic function with respect to frequency of heart rate and power of oscillations in the high-frequency diapason becomes evident only by the 3-week age.

First‐ and second‐generation H1 antihistamines: from the molecular basis of their interaction with HERG K+ channels to physiological and pathophysiological implication

SummaryThe present article reports on the recent findings addressing the molecular basis for some rare but serious cardiovascular side‐effects exerted by some non‐sedating H1‐blocking antihistamines. These latest developments, which have allowed fundamental insights into the role played by a specific class of potassium channels, the so‐called human ether‐a‐gogo‐related gene (HERG) channels, in the regulation of cardiac action potential duration and rhythm regulation, have also opened new areas of investigation into its participation in neuronal and endocrine (adenohypophyseal, chromaffin, and pancreatic) cells functioning.

Effects of seizure repetition on postictal and interictal neurocardiac regulation in the rat.

Human epilepsy is associated with abnormalities in cardiac regulation, as measured by reductions of heart rate variability (HRV) and approximate entropy (ApEn), but it is not known how these abnormalities are related to seizure experience. Baseline electrocardiogram (ECG) was recorded from seizure-naive rats. They were subjected daily to maximal electroshock (MES), which induced tonic seizures with hindlimb extension, for a total of 10 days. ECG was obtained for 30 min before and after the first and last seizure. R-R variability, spectral variability, and ApEn were calculated to determine changes in pre- and postictal cardiac regulation. Before the last seizure, interictal parameters were compared with baseline values to determine changes in interictal HRV as a consequence of seizure repetition. Postictal values obtained after the last seizure were compared with the initial postictal data to look for changes in postictal cardiac regulation. During the postictal state, a mild, but significant, loss of ApEn was present after either the first or last seizure. Seizure repetition induced loss of R-R variability and high-frequency spectral band, which was present both interictally and postictally. The results suggest that convulsive seizures are associated with an immediate reduction of the complexity of cardiac rhythm regulation, as reflected by reductions of ApEn. Seizure repetition may induce long-term neural abnormalities in neurocardiac regulatory systems, especially parasympathetic, which limit appropriate autonomic responses. These acquired abnormalities may, in turn, predispose individuals to cardiac arrhythmia and sudden unexpected death in epilepsy.

Effects of seizure severity and seizure repetition on postictal cardiac arrhythmia following maximal electroshock

Convulsive seizures triggered by maximal electroshock (MES) induce profound abnormalities in neural regulation of cardiac rhythm that are manifested by a period of marked cardiac arrhythmia in the immediate postictal state. It is not known whether seizure severity or seizure experience may influence the duration of cardiac arrhythmia in the postictal state. We varied the duration of MES administered to rats to vary seizure severity, as measured by the extensor to flexion ( E/ F) ratio. In separate experiments, rats were subjected to daily MES. Finally, we pretreated rats with ketamine prior to MES to block seizures hindlimb extension. In all animals, the R-R interval was plotted on the tachogram, and the duration of the arrhythmia was measured. Increases in MES duration increased significantly the E/ F ratio and prolonged significantly the postictal cardiac arrhythmia. Repetition of MES caused a kindling effect with respect to seizure severity resulting in a significant increase of the E/ F ratio and significant increases in the duration of postictal arrhythmia. Blocking of the hindlimb extension by ketamine abolished arrhythmia suggesting that the arrhythmia is not caused directly by MES. Severity of tonic convulsive seizures is a determinant of disordered cardiac autonomic regulation and directly influences the duration of cardiac arrhythmia during the immediate postictal state following MES. Seizure repetition also increases abnormalities of postictal neural regulation of the heart, but further studies are needed to determine whether this effect is independent of seizure severity increases.

Cardiac dynamics in corticotropin-releasing factor receptor subtype-2 deficient mice

The action of corticotropin-releasing factor (CRF) is mediated by two recently identified receptors, CRFR1 and CRFR2, that differ with respect to their anatomical distribution and pharmacologic ligand-binding properties. Here we show by an analysis of circadian heartbeat interval fluctuations that CRFR2-deficiency in mice does not interfere with the dynamical mechanisms underlying the control of heart rate. Hence, intact CRFR2 would not constitute an indispensable requirement of physiologic cardiac rhythm regulation. However, both CRFR2 knockout (−/−) and wildtype control (+/+) mice showed altered dynamical properties of cardiac interbeat fluctuations in contrast to homogenetic inbred strains of mice (C57BL/6N and C57BL/6J). The results stress the impact of genetic background and support the generalized notion that transgenic 129/Sv-derived knockout mice exhibit altered cardiac dynamics which is interpreted to reflect an attenuation of neuroautonomic sympatho-vagal antagonism.

Reaction of Cardiac Activity of Senior Pupils of Schools Providing Differentiated Education upon Examination Stress

Effects of examination stress on psychological characteristics and indices of the autonomic nervous system were studied in pupils of the eighth and tenth grades of high schools providing differential (test group, “Neuron” gymnasium) and general education (control group). General health state and levels of activity and mood (feeling, activity, mood; FAM) and neuroticism (according to Eysenck) were determined in both groups. Main hemodynamic indices (heart rate and blood pressure) were measured, and mathematical analysis of the heart rate by was performed according to Baevskii. Comparative analysis of psychophysiological tests and heart rate changes in the control and test groups points to a high tension in the cardiac rhythm regulation mechanisms and strong anxiety in schoolchildren in the differential education school. The character and depth of preexamination stress depended on the type of autonomic control of cardiac activity. Schoolchildren with sympathicotonic cardiac rhythm regulation showed the strongest emotional tension. Schoolchildren with the normotonic type of regulation were the most calm.

Sigma receptors: from discovery to highlights of their implications in the cardiovascular system.

Sigma receptors are the targets of many ligands, of which some (the haloperidol for instance) are psychoactive, and of substances known to have antiarrhythmic effects (amiodarone and clofilium). They are involved in a variety of cardiovascular functions, such as the regulation of cardiac contractility and rhythm and the regulation of coronary and peripheral arterial vasomotricity. This short review will focus on some aspects regarding the ligands, the binding sites, the intracellular coupling and the cardiovascular functions of these enigmatic receptors.

Influence of the Environment on the Physiological Status of Northerner Students

The authors examined students of specialized secondary education institutions of Syktyvkar during a three-year-long period. Some morphofunctional indices are worse in them than in similar cohorts in Central Russia. The unfavorable environmental situation impaired tolerance to hypoxemia, cardiac rhythm regulation, central hemodynamics, and balance of autonomic processes and affected dynamics of the physiological status of the body during social adaptation to learning.

Use of a physiological monitoring model for comprehensive evaluation of adaptive capacities in schoolchildren during learning activity. Part I. Influence of various motor activity regimens on cardiac rhythm induces in junior schoolchildren

The dynamics of changes in the indices of the autonomic regulation of cardiac rhythm was studied in junior schoolchildren during adaptation to physical exercise. An analysis of variation pulsometry parameters throughout the school year showed the role of the sympathetic and parasympathetic parts of the autonomic nervous system in the formation of body adaptive reactions to various motor activity regimens.

Cardiac Rhythm Regulation in Children during the Initial Period of School Education under Conditions of the North

Cardiac rhythm parameters recorded in healthy children during the initial weeks of schoolwork immediately after the transition from kindergarten to the first grade of the elementary school or from the elementary school to the fifth grade of the middle school showed that their regulatory systems were stressed to different degrees, reflecting different costs of adaptation to environmental conditions. The most pronounced changes in these parameters were observed in the first graders: because of more significant stress (sometimes, overstress) of their regulatory mechanisms, in 70% of these children complete adaptation to new living conditions was associated with greater physiological costs. In the fifth graders, a similar situation was observed only in 25% of the children examined. The less pronounced physiological changes observed in 30% of the first graders and in 75% of the fifth graders can be related to the more mature state of their cardiac regulatory mechanisms, as well as to their greater adaptability to environmental conditions during the period examined.

Autonomic Regulation of Cardiac Rhythm in 7- to 16-Year-Old Children Survivors of Oncological Disease

Autonomic Regulation of Cardiac Rhythm in 7- to 16-Year-Old Children Survivors of Oncological Disease