Sinoatrial Conduction Research Articles

Sinoatrial node function and the role of sinoatrial conduction in the typical atrial flutter substrate

BackgroundSinoatrial node (SAN) activation and sinoatrial conduction pathways (SACPs) have been assessed in animals but not in humans. ObjectivesWe used ultrahigh-density mapping and simulated models to characterize the SAN and to investigate whether slowed SAN conduction may contribute to the atrial flutter (AFL) substrate. MethodsTwenty-seven patients undergoing electrophysiologic procedures had right atrial mapping. SAN activation patterns and conduction block were analyzed. The interaction between the SAN and the intercaval line of block (LOB) was analyzed, and right atrial simulations with different degrees of block were created to investigate arrhythmia mechanisms. ResultsFifteen AFL patients and 12 reference patients were enrolled. SACPs were identified in all patients with sinus rhythm maps. An SAN-adjacent LOB was observed in AFL patients. SAN conduction velocity was slower in AFL vs reference (0.60 m/s [0.56–0.78 m/s] vs 1.13 m/s [1.00–1.21 m/s]; P = .0021). Coronary sinus paced maps displayed an intercaval LOB in AFL patients but not in reference patients, which was completed superiorly by the SAN-adjacent LOB. Corrected sinus node recovery time was longer in AFL patients (552.3 ± 182.9 ms vs 325.4 ± 138.3 ms; P < .006) and correlated with degree of intercaval block (r = 0.7236; P = .0003). Computer modeling supported an important role of SAN-associated block in the flutter substrate. ConclusionUltrahigh-density mapping accurately identifies SAN activation and SACPs. The LOB important for typical AFL was longer in AFL patients, and when partial, it was always present inferiorly and completed superiorly because of slowed conduction across the SAN. Corrected sinus node recovery time correlated with intercaval block, suggesting a role for SAN disease in the genesis of the typical AFL substrate.

Use of machine learning and Poincaré density grid in the diagnosis of sinus node dysfunction caused by sinoatrial conduction block in dogs.

Sinus node dysfunction because of abnormal impulse generation or sinoatrial conduction block causes bradycardia that can be difficult to differentiate from high parasympathetic/low sympathetic modulation (HP/LSM). Beat-to-beat relationships of sinus node dysfunction are quantifiably distinguishable by Poincaré plots, machine learning, and 3-dimensional density grid analysis. Moreover, computer modeling establishes sinoatrial conduction block as a mechanism. Three groups of dogs were studied with a diagnosis of: (1) balanced autonomic modulation (n = 26), (2) HP/LSM (n = 26), and (3) sinus node dysfunction (n = 21). Heart rate parameters and Poincaré plot data were determined [median (25%-75%)]. Recordings were randomly assigned to training or testing. Supervised machine learning of the training data was evaluated with the testing data. The computer model included impulse rate, exit block probability, and HP/LSM. Confusion matrices illustrated the effectiveness in diagnosing by both machine learning and Poincaré density grid. Sinus pauses >2 s differentiated (P < .0001) HP/LSM (2340; 583-3947 s) from sinus node dysfunction (8503; 7078-10 050 s), but average heart rate did not. The shortest linear intervals were longer with sinus node dysfunction (315; 278-323 ms) vs HP/LSM (260; 251-292 ms; P = .008), but the longest linear intervals were shorter with sinus node dysfunction (620; 565-698 ms) vs HP/LSM (843; 799-888 ms; P < .0001). Number and duration of pauses, not heart rate, differentiated sinus node dysfunction from HP/LSM. Machine learning and Poincaré density grid can accurately identify sinus node dysfunction. Computer modeling supports sinoatrial conduction block as a mechanism of sinus node dysfunction.

Historical development of diagnosis of bradyarrhythmias : The early years of clinical electrophysiology in Germany

The introduction of His bundle electrography by Benjamin Scherlag (New York) in 1969, together with programmed stimulation of the heart by Philip Coumel (Paris) in 1967, and Hein Wellens (Amsterdam) in 1972, were decisive turning points on the way to invasive electrophysiology and the development of an independent, now distinctly interventional subspecialty of cardiology. The main topic of the 1970s was bradycardic arrhythmias, promoted by pacemaker therapy, which had been introduced just over 10years earlier. The recording of the potentials of the bundle of His and other recording locations in the atria and ventricles allowed adifferentiated assessment of the excitation process and the refractory periods. High-rate atrial stimulation to determine sinus node recovery time and premature stimulation to determine sinoatrial conduction time were developed to analyze sinoatrial node function. This article describes the introduction of His bundle electrography in agradually increasing number of centers in Germany and their scientific contribution.

Mechanistic insight into the functional role of human sinoatrial node conduction pathways and pacemaker compartments heterogeneity: A computer model analysis.

The sinoatrial node (SAN), the primary pacemaker of the heart, is responsible for the initiation and robust regulation of sinus rhythm. 3D mapping studies of the ex-vivo human heart suggested that the robust regulation of sinus rhythm relies on specialized fibrotically-insulated pacemaker compartments (head, center and tail) with heterogeneous expressions of key ion channels and receptors. They also revealed up to five sinoatrial conduction pathways (SACPs), which electrically connect the SAN with neighboring right atrium (RA). To elucidate the role of these structural-molecular factors in the functional robustness of human SAN, we developed comprehensive biophysical computer models of the SAN based on 3D structural, functional and molecular mapping of ex-vivo human hearts. Our key finding is that the electrical insulation of the SAN except SACPs, the heterogeneous expression of If, INa currents and adenosine A1 receptors (A1R) across SAN pacemaker-conduction compartments are required to experimentally reproduce observed SAN activation patterns and important phenomena such as shifts of the leading pacemaker and preferential SACP. In particular, we found that the insulating border between the SAN and RA, is required for robust SAN function and protection from SAN arrest during adenosine challenge. The heterogeneity in the expression of A1R within the human SAN compartments underlies the direction of pacemaker shift and preferential SACPs in the presence of adenosine. Alterations of INa current and fibrotic remodelling in SACPs can significantly modulate SAN conduction and shift the preferential SACP/exit from SAN. Finally, we show that disease-induced fibrotic remodeling, INa suppression or increased adenosine make the human SAN vulnerable to pacing-induced exit blocks and reentrant arrhythmia. In summary, our computer model recapitulates the structural and functional features of the human SAN and can be a valuable tool for investigating mechanisms of SAN automaticity and conduction as well as SAN arrhythmia mechanisms under different pathophysiological conditions.

Ultra-High Density Electroanatomic Mapping of Sinoatrial Conduction Pathways and the Role of Sinoatrial Node Remodelling in the Atrial Arrhythmia Substrate

Ultra-High Density Electroanatomic Mapping of Sinoatrial Conduction Pathways and the Role of Sinoatrial Node Remodelling in the Atrial Arrhythmia Substrate

Abstract 15525: Resolving Human Sinoatrial Node Leading Pacemaker vs Atrial Early Activation Sites by 3D High Resolution Imaging to Guide Ablation Treatment of Atrial Arrhythmia

Introduction: Surgical/ablation treatment for atrial arrhythmias such as anatomic sinoatrial node (SAN) tachycardia and atrial fibrillation either target or preserve the SAN. However, defining SAN is challenging because clinical electrophysiological (EP) mapping can visualize only exits of SAN activation as early activation sites (EAS) and not the leading pacemaker (LP) within the 3D intramural SAN. Methods: High resolution (300-900μm 2 ) including epi/endocardial (Epi/Endo) dual sided near infrared optical mapping (NIOM) was conducted on coronary perfused explanted human atria (n=26, 19-69 y.o.). SAN was defined by optical action potential morphologies as the region of slow diastolic depolarization (slow upstroke) preceding atrial excitation. Serial histology and contrast enhanced MRI (CE-MRI, 100μm 3 resolution) were used to define the 3D fibrotic structure of the SAN pacemaker complex. Results: During sinus rhythm (SR) (83±22 bpm), the LP was primarily located in the SAN center. Electrical impulses exit from SAN to atria through 1-2 sinoatrial conduction pathways (SACP), leading to discrete EAS along crista terminalis (CT), preferentially from lateral superior/middle SACPs. The distance between SAN LP and EAS varied from 3.5-23 mm. Heterogeneous atrial wall thickness, fibrosis content and myofiber orientation along the SAN and CT (5-15mm thick) regions led to complex intramural conduction from SAN LP to EAS and substantial Epi-Endo activation dyssynchrony. Conclusions: EAS visualized on both Epi/Endo mapping mainly distributed along thick CT, but not on the surface projection of SAN, due to intramural fiber orientation of preferential SACPs. The higher fibrotic content in the human SAN than CT detected by CE-MRI, integrated with EP mapping can be helpful to accurately define SAN structure and pathways for reentrant SAN arrhythmias ablations.

Role of Endothelin-1 in Right Atrial Arrhythmogenesis in Rabbits with Monocrotaline-Induced Pulmonary Arterial Hypertension.

Atrial arrhythmias are considered prominent phenomena in pulmonary arterial hypertension (PAH) resulting from atrial electrical and structural remodeling. Endothelin (ET)-1 levels correlate with PAH severity and are associated with atrial remodeling and arrhythmia. In this study, hemodynamic measurement, western blot analysis, and histopathology were performed in the control and monocrotaline (MCT, 60 mg/kg)-induced PAH rabbits. Conventional microelectrodes were used to simultaneously record the electrical activity in the isolated sinoatrial node (SAN) and right atrium (RA) tissue preparations before and after ET-1 (10 nM) or BQ-485 (an ET-A receptor antagonist, 100 nM) perfusion. MCT-treated rabbits showed an increased relative wall thickness in the pulmonary arterioles, mean cell width, cross-sectional area of RV myocytes, and higher right ventricular systolic pressure, which were deemed to have PAH. Compared to the control, the spontaneous beating rate of SAN–RA preparations was faster in the MCT-induced PAH group, which can be slowed down by ET-1. MCT-induced PAH rabbits had a higher incidence of sinoatrial conduction blocks, and ET-1 can induce atrial premature beats or short runs of intra-atrial reentrant tachycardia. BQ 485 administration can mitigate ET-1-induced RA arrhythmogenesis in MCT-induced PAH. The RA specimens from MCT-induced PAH rabbits had a smaller connexin 43 and larger ROCK1 and phosphorylated Akt than the control, and similar PKG and Akt to the control. In conclusion, ET-1 acts as a trigger factor to interact with the arrhythmogenic substrate to initiate and maintain atrial arrhythmias in PAH. ET-1/ET-A receptor/ROCK signaling may be a target for therapeutic interventions to treat PAH-induced atrial arrhythmias.

Targeted Treatment of Inappropriate Sinoatrial Node Tachycardia Based on Electrophysiological and Structural Mechanisms

The purpose of this review is to determine the causal mechanisms and treatment of inappropriate sinoatrial tachycardia (IST), defined as a non-physiological elevation in resting heart rate. IST is defined as a resting daytime sinus rate >100 beats/minute and an average 24-hour heart rate >90 beats/minute. Potential causal mechanisms include sympathetic receptor hypersensitivity, blunted parasympathetic tone, or enhanced intrinsic automaticity within the sinoatrial node (SAN) pacemaker-conduction complex. These anomalies may coexist in the same patient. Recent ex-vivo near-infrared transmural optical imaging of the SAN in human and animal hearts provides important insights into the functional and molecular features of this complex structure. In particular, it reveals the existence of preferential sinoatrial conduction pathways that ensure robust SAN activation with electrical conduction. The mechanism of IST is debated because even high-resolution electroanatomical mapping approaches cannot reveal intramural conduction in the 3-dimensional SAN complex. It may be secondary to enhanced automaticity, intranodal re-entry, or sinoatrial conduction pathway re-entry. Different pharmacological approaches can target these mechanisms. Long-acting β blockers in IST can act on both primarily increased automaticity and dysregulated autonomic system. Ivabradine targets sources of increased SAN automaticity. Conventional or hybrid ablation may target all the described abnormalities. This review provides a state-of-the-art overview of putative IST mechanisms. In conclusion, based on current knowledge, pharmacological and ablation approaches for IST, including the novel hybrid SAN sparing ablation, are discussed.

In vivo and ex vivo electrophysiological study of the mouse heart to characterize the cardiac conduction system, including atrial and ventricular vulnerability.

The mouse is a common and cost-effective animal model for basic research, and the number of genetically engineered mouse models with cardiac phenotype is increasing. In vivo electrophysiological study in mice is similar to that performed in humans. It is indispensable for acquiring intracardiac electrocardiogram recordings and determining baseline cardiac cycle intervals. Furthermore, the use of programmed electrical stimulation enables determination of parameters such as sinoatrial conduction time, sinus node recovery time, atrioventricular-nodal conduction properties, Wenckebach periodicity, refractory periods and arrhythmia vulnerability. This protocol describes specific procedures for determining these parameters that were adapted from analogous human protocols for use in mice. We include details of ex vivo electrophysiological study, which provides detailed insights into intrinsic cardiac electrophysiology without external influences from humoral and neural factors. In addition, we describe a heart preparation with intact innervation by the vagus nerve that can be used as an ex vivo model for vagal control of the cardiac conduction system. Data acquisition for in vivo and ex vivo electrophysiological study takes ~1 h per mouse, depending on the number of stimulation protocols applied during the procedure. The technique yields highly reliable results and can be used for phenotyping of cardiac disease models, elucidating disease mechanisms and confirming functional improvements in gene therapy approaches as well as for drug and toxicity testing.

Insights into sinus arrhythmia of the dog: Acetylcholine perfusion of canine right atrium results in beat-to-beat patterns that mimic sinus arrhythmia supporting exit block in the sinoatrial conduction pathways

Sinus arrhythmia of the dog is unique because of the pronounced alternating beat-to-beat intervals. The clustering of these short (faster rates) and long (slower rates) intervals is not just influenced by autonomic input from breathing; sinus arrhythmia can persist in the panting or apneic dog. The multiplicity of central and peripheral influences on the sinus node complicates the unraveling of the mechanisms of sinus arrhythmia. Studies of the sinus node suggest that acetylcholine can slow cellular depolarization and block sinoatrial conduction. Electrocardiographic monitoring of the dog supports this notion in that abrupt bifurcation into short and long intervals develop at lower heart rates. We sought to determine whether this phenomenon could be recapitulated in canine atrial preparations perfused with acetylcholine and whether selective pharmacologic blockade of the voltage and calcium clocks could provide insight into its mechanism. Spontaneous beat to beat (A–A) intervals were obtained from monophasic action potential recordings of perfused canine right atrial preparations before and during perfusion with acetylcholine (2−5 μM). The calcium clock was blocked with ryanodine (2−3 μM). The membrane clock was blocked with diltiazem hydrochloride (ICa,L blocker; 0.25 μM) and ZD7288 (If blocker; 3 μM). Hyperpolarization was hindered by blockade of IK,Ado/IK,Ach with tertiapin Q (100 nM) before and during acetylcholine perfusion.Acetylcholine resulted in beat clusters similar to those seen in sinus arrhythmia of the dog. Beat clusters were consistent with intermittent 2:1 and 3:1 sinoatrial conduction block. Tertiapin Q abolished this patterning suggesting a role of IK,Ado/IK,ACh in the mechanism of these acetylcholine-induced beat-to-beat patterns.

Sinoatrial conduction abnormalities - an underestimated cardiac complication in women with systemic sclerosis.

IntroductionIt has been claimed that patients with systemic sclerosis (SSc) have an increased risk of developing cardiac arrhythmias and atrioventricular conduction disorders, but it is unknown whether SSc may be a cause of sinoatrial conduction abnormalities.AimTo establish the incidence of sinoatrial conduction abnormalities in patients with SSc and verify the relationship of these disorders with various clinical descriptors of SSc.Material and methodsForty women with systemic sclerosis of varying duration and severity underwent 24-hour ambulatory ECG monitoring. The occurrence of type I second-degree sinoatrial block (SA-block) and calculation of sinoatrial conduction time (SACT) were evaluated to establish the incidence of sinoatrial conduction abnormalities. The measurements of SACT were obtained using spontaneous atrial premature beats. The effect of various clinical descriptors on sinoatrial conduction abnormalities was assessed.ResultsThe mean ± SD SACT for the 40 patients was 150 ±15 ms. Prolonged (> 150 ms) SACT was found in 20 patients. In 14 (35%) patients SA-block occurred during ambulatory ECG monitoring. The discriminant analysis identified the severity of SSc cutaneous manifestation as an independent marker for developing SA-block (p < 0.005) and SACT prolongation (p < 0.0002).ConclusionsPatients with SSc are at an increased risk of developing type I second-degree sinoatrial block and prolonged sinoatrial conduction time. The occurrence of these abnormalities is related to the severity of skin involvement. Therefore, cardiological diagnosis using 24-hour ambulatory ECG in this group of patients should be focused also on this type of disorders. Prospective, controlled studies are needed to assess their prognostic role.

The Genetic Dissection of Ace2 Expression Variation in the Heart of Murine Genetic Reference Population.

Background: A high inflammatory and cytokine burden that induces vascular inflammation, myocarditis, cardiac arrhythmias, and myocardial injury is associated with a lethal outcome in COVID-19. The SARS-CoV-2 virus utilizes the ACE2 receptor for cell entry in a similar way to SARS-CoV. This study investigates the regulation, gene network, and associated pathways of ACE2 that may be involved in inflammatory and cardiovascular complications of COVID-19.Methods: Cardiovascular traits were determined in the one of the largest mouse genetic reference populations: BXD recombinant inbred strains using blood pressure, electrocardiography, and echocardiography measurements. Expression quantitative trait locus (eQTL) mapping, genetic correlation, and functional enrichment analysis were used to identify Ace2 regulation, gene pathway, and co-expression networks.Results: A wide range of variation was found in expression of Ace2 among the BXD strains. Levels of Ace2 expression are negatively correlated with cardiovascular traits, including systolic and diastolic blood pressure and P wave duration and amplitude. Ace2 co-expressed genes are significantly involved in cardiac- and inflammatory-related pathways. The eQTL mapping revealed that Cyld is a candidate upstream regulator for Ace2. Moreover, the protein–protein interaction (PPI) network analysis inferred several potential key regulators (Cul3, Atf2, Vcp, Jun, Ppp1cc, Npm1, Mapk8, Set, Dlg1, Mapk14, and Hspa1b) for Ace2 co-expressed genes in the heart.Conclusions: Ace2 is associated with blood pressure, atrial morphology, and sinoatrial conduction in BXD mice. Ace2 co-varies with Atf2, Cyld, Jun, Mapk8, and Mapk14 and is enriched in the RAS, TGFβ, TNFα, and p38α signaling pathways, involved in inflammation and cardiac damage. We suggest that all these novel Ace2-associated genes and pathways may be targeted for preventive, diagnostic, and therapeutic purposes in cardiovascular damage in patients with systemic inflammation, including COVID-19 patients.

Ictal ECG changes and antiepileptic drug therapy

Abstract Purpose Epileptic seizures may cause severe cardiac arrhythmias. Most people with epilepsy die suddenly and whose death is recognized to a sudden unexpected death in epilepsy (SUDEP). There are controversial reports on the association between polytherapy using antiepileptic drugs and SUDEP. First-line drugs include, in particular, carbamazepine, oxcarbazepine, and lamotrigine, which are sodium channel blockers that may impair heart function. Often a patient requires a combination of antiepileptic drugs Methods 204 patients with epilepsy and were on antiepileptic drugs therapy. The ECG cardiac monitor was implanted in all patients (n=204) and was analyzed together with the preclinical data including age, sex, family history, cardiac risk factors (hypertension, dyslipidemia, diabetes mellitus), heart disease, antiepileptic drug type. Results After a follow-up of 12-month ictal ECG changes (rhythm and conduction disturbances, ST segment abnormalities) were observed in 134 (66%) patients, and only in 70 (34%) – without ictal ECG changes, the average age in these groups was 34,4±9,9 and 36,7±11,8 years (p&amp;gt;0,05). In the group with ictal ECG changes among patients receiving as monotherapy antiepileptic drugs, ictal ECG changes were found in 53.7% of cases, with polytherapy antiepileptic drugs significantly more often – in 71.5% of cases (p&amp;lt;0.05). a reliable association between carbamazepine and changes in sinoatrial and atrioventricular conduction (p=0.01) was significant. In the analyzed group of patients, carbamazepine therapy was also associated with the presence of ictal ST-segment abnormalities (depression/elevation) (p=0.013). A positive association was observed between the administration of oxcarbazepine and development of ictal tachycardia (p=0.04) and ictal right and left bundle branch block, which was observed in 71.4% of cases against the background of oxcarbazepine, significantly more often than with other drugs (p=0.005). Conclusion In agreement with previous publications available in the literature, our results confirm the risk of high-frequency rhythm and conduction disturbances, ST segment abnormalities related to antiepileptic drugs, in particular, carbamazepine and oxcarbazepine and indicates the need of not only cardiological examination before prescribing an antiepileptic drugs, but also a thorough follow-up during the therapy. Patients with ictal ECG changes, primarily rhythm and conduction disturbances, should be under the dynamic control of not only neurologists but also cardiologists and require regular cardiological check-up (ECG, Holter monitoring of the electrocardiogram, echocardiography). Funding Acknowledgement Type of funding source: None

Propofol suppresses the His-ventricular conduction in paediatric patients.

What is known and objectivePropofol is the most commonly used intravenous anaesthetic worldwide and is considered to be safe for all ages. However, there have been some reports that propofol induces severe atrioventricular (AV) blocks in humans and some studies demonstrated that propofol suppressed the cardiac conduction system in animals. A precise mechanism by which the block is induced has not been elucidated yet in humans. The objective of this study was to investigate the effects of propofol on the cardiac conduction system and the cardiac autonomic nervous balance in children.MethodsWe enrolled 23 paediatric patients (age: 6‐15 years; males: 16, females: 7) who were scheduled to undergo radiofrequency catheter ablation (RFCA) under general anaesthesia. Anaesthesia was induced with 2 mg/kg propofol and 0.5 µg/kg/min remifentanil, and tracheal intubation was performed with the aid of 1 mg/kg rocuronium. Anaesthesia was maintained with 5‐7 mg/kg/h propofol and 0.2 µg/kg/min remifentanil during the RFCA. After the completion of the RFCA, anaesthesia was further maintained with 5 mg/kg/h propofol and 0.2 µg/kg/min remifentanil for at least 10 min (LC: low propofol concentration state), followed by the injection of 2 mg/kg propofol and the infusion of 10 mg/kg/h propofol for 10 min (HC: high propofol concentration state). The sinus node recovery time (SNRT), sinoatrial conduction time (SACT), atrial‐His (AH) interval and the His‐ventricular (HV) interval were measured at the end of both the LC and HC. Cardiac autonomic regulation was simultaneously assessed based on heart rate variability.Results and discussionPropofol significantly suppressed intrinsic cardiac HV conduction, but did not affect the SNRT, SACT or the AH interval. As HV blocks, which occur below the His bundle, are often life‐threatening, the HV conduction delay may be a cause of severe AV blocks induced by propofol. Propofol directly suppressed parasympathetic nerve activity, and sympathetic nerve activity was also suppressed.What is new and conclusionThese results indicate that propofol suppresses the HV conduction and might help to elucidate the mechanism by which propofol causes lethal AV blocks.

Bradycardia and pacemakers

Bradyarrhythmias are frequently encountered in primary care; they comprise various rhythm disturbances including sinoatrial node and atrioventricular conduction disorders. Clinical presentation varies from a wide range of symptomatic presentations including dizziness, syncope, dyspnoea, fatigue and heart failure symptoms to the asymptomatic, incidental finding. Diagnosing patients correctly including a symptom–rhythm correlation is important, especially as some carry a risk of sudden death. In this article we will discuss disease states, diagnosis, referral and an essential guide to cardiac pacemakers, the primary lifelong treatment option for selected patients without reversible causes.

Dysautonomia in a Bitch with Hypothyroidism

Background: Thyroid hormones have important effects on the cardiovascular system, of which the main ones are the increase in the heart response to the autonomic sympathetic nervous system. Heart rate variability is a non-invasive method of assessing autonomic heart modulation, thus being an important form of evaluation in patients with thyroid dysfunctions. This study aimed to report electrocardiographic and heart rate variability data of a dog with hypothyroidism that presented a parasympathetic dysfunction.Case: A 7-year-old female Dalmatian dog was admitted for clinical evaluation in Fortaleza, Brazil. According to the owner, she had been apathetic for a year, had gained weight, always had a sad expression, and her hair was generally brittle and opaque. On physical examination, skin lesions were observed at the end of the spine, extending to the tail region, with the latter showing total alopecia. Low T4 levels confirmed the diagnosis of primary hypothyroidism. Then, a 24-h Holter monitoring was performed, which showed that the animal had sinus arrhythmia associated with moments of second-degree sinoatrial block and rare moments of sinus tachycardia. In addition, moments of premature multifocal ventricular extrasystoles and 1st-degree atrioventricular block were observed. Based on the Holter results, heart rate variability (HRV) was calculated. Regarding the HRV in the frequency domain, 32.16 was obtained in the low frequency (LF) band, 67.84 in the high frequency (HF) band, and the LF / HF ratio was 0.46, with a total power of 5205. As for the HRV in the time domain, RMSSD was 117, pNN50 was 62.64 and SDNN was 384. This showed an increase in the parasympathetic activity of the heart and, due to this increased activity, a second-degree sinoatrial block occurred, which is a sinus function disturbance resulting from the exacerbated parasympathetic activity.Discussion: Beta-adrenergic receptors have their expression and activity altered by thyroid hormones. The sympathetic stimulation on the heart through the activation of these receptors originates a positive inotropic, lusitropic, dromotropic and chronotropic effect. Therefore, in the absence of thyroid hormones, there is a decrease in this stimulation, thus allowing a preponderant parasympathetic tone. In the present report, the increase in the parasympathetic tonus, observed in hypothyroidism, resulted in a reduction in the frequency of sinus firing, slowing of intranodal and sinoatrial conduction, and shortening of the effective refractory period, a combination of factors that led to decreased HR observed in the Holter monitoring. Previous studies have shown that thyroid hormones increase sympathetic activity, mainly in the heart, since they do not act by increasing the production or release of catecholamines, but rather increasing catecholamine response on the heart, due to a positive regulation of Ca2+-ATPase channels of the sarcoplasmic reticulum and beta1-adrenergic receptors. Thus, the observed result was already expected, because in hypothyroidism there is a decrease in these hormones that increase the sympathetic activity on the heart and so, the parasympathetic tone was very evident. The study of heart rate variability allows the simple assessment of the autonomic nervous system imbalance, and may be extremely important in the follow-up of diseases that affect this balance, such as hypothyroidism. Hence, more studies are required to verify the effect of such diseases on heart rate variability, aiming to define associations between the diseases and the alterations, as well as to define parameters of normality for such examinations.

Two methods for modeling of sick sinus syndrome in rats: Ischemia reperfusion and sodium hydroxide induced injury

The Sick Sinus Syndrome (SSS) is a serious life-threatening heart disease. It is important to establish a credible and stable sinus node damage model. In this study, we use two methods to construct an SSS damage model in rats. One is to inject sodium hydroxide to the SSS area through internal jugular vein. Another is to cause ischemia-reperfusion injury on the SSS area. 43 healthy SD rats were randomly divided into 4 groups, namely ischemia-reperfusion injury group (IRIG), inject sodium hydroxide group (ISHG), and propranolol group (PG) and the control group (CG). The achievement ratio of modeling was 67% in the IRIG and 83% in the ISHG. The HR significantly decreased after operation in the IRIG and ISHG compared with pre-operation (P＜0.01). The HR was reduced by above 30% in these 2 groups after modeling, while the reduction was better maintained in IRIG. Additionally, the sinoatrial node recovery time (SNRT) and sinoatrial conduction time (SACT) were significantly prolonged compared with pre-modeling in 2 groups (P < 0.01). Morphology results showed blurry in structure and boundaries with pale cytoplasm. It is speculated that IRIG and ISHG modeling might influence the calcium concentration and damage the sinus node function by decrease the expression of HCN4 and SCN5A, which impaired the driving ability of sinus node and leading to apoptosis. Ischemia reperfusion injury and sodium hydroxide injury could construct stable SSS models which could represent clinic pathological damage. Thus, both methods could be used for further studies of the SSS mechanisms and drugs.

Electrophysiological effects of desflurane in children with Wolff-Parkinson-White syndrome: a randomized crossover study.

We hypothesized that, compared with propofol, desflurane prolongs the antegrade accessory pathway effective refractory period (APERP) in children undergoing radiofrequency catheter ablation for Wolff-Parkinson-White (WPW) syndrome. In this randomized crossover study, children aged 4.1-16.1years undergoing radiofrequency catheter ablation for WPW syndrome were randomly divided into four groups according to the concentration of desflurane and anesthetics used in the first and the second electrophysiological studies (EPS). After induction of general anesthesia with propofol and tracheal intubation, they received one of the following regimens: 0.5 minimum alveolar concentration (MAC) desflurane (first EPS) and propofol (second EPS) (Des0.5-Prop group, n=8); propofol (first EPS) and 0.5 MAC desflurane (second EPS) (Prop-Des0.5 group, n=9); 1 MAC desflurane (first EPS) and propofol (second EPS) (Des1.0-Prop group, n=10); propofol (first EPS) and 1 MAC desflurane (second EPS) (Prop-Des1.0 group, n=9). Radiofrequency catheter ablation was performed upon completion of EPS. Sample size was determined to detect a difference in the APERP. Desflurane at 1.0 MAC significantly prolonged the APERP compared with propofol, but did not affect the sinoatrial conduction time, atrio-His interval or atrioventricular node effective refractory period. Supraventricular tachycardia was induced in all children receiving propofol, but not induced in 1 and 4 children receiving 0.5 MAC and 1.0 MAC desflurane, respectively. Desflurane enhances the refractoriness and may block the electrical conduction of the atrioventricular accessory pathway, and is therefore not suitable for use in children undergoing radiofrequency catheter ablation for WPW syndrome.

Incidence of sinus node dysfunction in patients with long-standing, persistent atrial fibrillation who require simultaneous surgical correction of mitral and tricuspid valve defects and the "Maze IIIB" procedure

Atrial fibrillation (AF) is the most common disorder of heart rhythm. A series of "Maze" surgery was developed, among which the "Maze III" modification is presently a gold standard for surgical treatment of AF. To study the sinoatrial node (SAN) function before and after the "Maze III" surgery. The study included 100 patients (48 males) with persistent and long-standing persistent AF and valve abnormality. Mean age of patients was 59 years and mean AF duration - 4 years. Tachysystolic AF prevailed (62 %); normosystolic AF was observed in 31 % of patients; and bradysystolic - in 7 % of patients. Electric cardioversion was performed for all patients according to the standard method. After successful recovery of the sinus rhythm, the endocardial electrophysiological study (EPS) of the heart was performed. Correction of valve pathology and the "Maze IIIB" surgery were performed on days 1-2 following EPS. The SAN function was evaluated by the time of function recovery (SAN TFR). Using electric cardioversion, the sinus rhythm was restored in all patients. EPS showed abnormal prolongation of the corrected time for the SAN function recovery (CTSANFR) and sinoatrial conduction time (SACT) in 11 % of patients. In 2 % of patients, the abnormal prolongation of SACT was an isolated conduction disorder. In total, 13 % of patients had SAN dysfunction (SAND). These patients received implantable electric cardioverters after a surgical intervention (correction of valve abnormality and "Maze III"). The sinus rhythm recovered immediately after the surgery. On day 7, steady sinus rhythm was observed in 46 % of patients. During the postperfusion period and on the first day postsurgery, 62 % of patients had replacement atrioventricular nodal rhythm. By the time of discharge from the hospital, the nodal rhythm was observed in 25 % of patients. Starting from day 2, the replacement atrial rhythm developed in 13 % of patients, and by the time of discharge from the hospital, 24 % of patients had a stable atrial rhythm. Effectiveness of the surgical treatment for persistent and long-standing persistent AF (modified "Maze IIIB" surgery with simultaneous correction of the mitral valve (MV) and the tricuspid valve (TV)) in the early postsurgery period was 95 %. According to data of preoperative endocardial EPS, SAND was observed in 13 % of patients. Following the surgical correction of MV and TV defects and the criomodification of the "Maze IIIB" surgery, signs of SAND requiring implantation of an electric cardioverter were observed in a total of 24 % of patients.

Adrenomedullin Stimulates Porcine Sinus Node Automaticity

Adrenomedullin (AM) is a vasodilatory and chronotropic peptide that has cardioprotective properties in settings of ischemia-reperfusion. Specifically, the 52-amino acid peptide hormone has been shown to reduce infarct size and potentially be protective against malignant arrhythmias. AM reduces L-type calcium currents in rabbit ventricular myocytes, and can possibly be utilized as an antiarrhythmic drug. However, at present it is unclear whether AM has cardiac electrophysiological effects in vivo. In the present study, we investigated whether AM affects sinus and atrioventricular nodal functions, cardiac pacing thresholds, refractory properties and intracardiac conduction intervals in an intact porcine model (Norwegian landrace and Yorkshire hybrids; n=12). Hemodynamic and electrophysiological parameters were recorded at baseline and following 60 min of AM-infusion (100 ng/kg/min). The hemodynamic effects of AM were characterized by a reduced mean arterial pressure (76 ± 9 vs. 57 ± 6; p<0.05; mmHg), tachycardia (91 ± 13 vs. 112 ± 15; p<0.05; beats/min) and an augmented cardiac index (131 ± 20 vs. 176 ± 28; p<0.05; ml/min/kg). The sinus cycle length was reduced (674 ± 89 vs. 546 ± 73; p<0.05; ms), sinoatrial conduction time was unaltered (79 ± 24 vs. 72 ± 19; ns; ms), and the sinus node recovery time (SNRT) was reduced at paced cycle lengths of 425 ms, 375 ms and 325 ms (average SNRT 1034 ± 449 vs.704 ± 141; p<0.05; ms). Diastolic pacing thresholds, effective refractory periods, Wenckebach cycle length and intracardiac conduction intervals were unaffected by AM. In conclusion, AM stimulates sinus node function with a reduced sinus cycle length and increased automaticity but has no further detectable intracardiac electrophysiological effects. Whether the increased automaticity is a direct effect on the sinus node or an indirect effect mediated through the autonomic nervous system remains to be determined.