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Sick sinus syndrome (SSS) encompasses a group of conduction disorders characterized by the inability of sinoatrial node to perform its pacemaker function. Our aim was to identify genetic predictors of SSS in a prospective cohort of patients admitted to the clinic for pacemaker implantation using single-locus and multilocus approaches. We performed genotyping for polymorphic markers of CLCNKA (rs10927887), SCN10A (rs6795970), FNDC3B (rs9647379), MIR146A (rs2910164), SYT10 (rs7980799), MYH6 (rs365990), and KCNE1 (rs1805127) genes in the group of 284 patients with SSS and 243 healthy individuals. Associations between the studied loci and SSS were tested using logistic regression under recessive genetic model using sex and age as covariates. Multilocus analysis was performed using Markov chain Monte Carlo method implemented in the APSampler program. Correction for multiple testing was performed using Benjamini–Hochberg procedure. We detected an individual association between KCNE1 rs1805127*A allele and SSS in the total study group (OR 0.43, PFDR = 0.028) and in the subgroup of patients with 2nd or 3rd degree sinoatrial block (OR 0.17, PFDR = 0.033), and identified seven allelic patterns associated with the disease. SCN10A rs6795970*T and MIR146A rs2910164*C alleles were present in all seven combinations associated with SSS. The highest risk of SSS was conferred by the combination SCN10A rs6795970*T+FNDC3B rs9647379*C+MIR146A rs2910164*C+SYT10 rs7980799*C+KCNE1 rs1805127*G (OR 2.98, CI 1.77–5.00, P = 1.27 × 10–5, PFDR = 0.022). Our findings suggest that KCNE1 rs1805127 polymorphism may play a role in susceptibility to sinoatrial node dysfunction, particularly presenting as 2nd or 3rd degree sinoatrial block, and the risk-modifying effect of other studied loci is better detected using multilocus approach.

The symptomatic sick sinus syndrome presents a classic indication for the implantation of a dual-chamber pacemaker according to the current national and international guidelines. However, in cases where dizziness and near syncope due to a sinus node dysfunction are found together with clinical characteristics of a sleep apnea-hypopnea syndrome (SAHS), screening for sleep apnea would be prudent before deciding for a pacemaker. The case report presented herein describes a patient with symptomatic sinus bradycardia and second-degree SA block with a Wenckebach periodicity, in whom the primary decision to implant a pacemaker was altered in favor of treatment with nCPAP (nasal continuous positive airway pressure) because after a careful and thorough evaluation of the patient’s history and symptoms, a severe mixed SAHS was diagnosed. On diagnosing SAHS with an obstructive component in patients with symptomatic bradycardia and SA block, there is no primary need for a pacemaker, but rather for implementing treatment with nCPAP. Thus, a pacemaker should only be considered in patients with intolerance or bad compliance regarding nCPAP, or in those in whom no significant reduction of bradyarrhythmia is achieved.

Hundred years ago, in 1907, A. Keith and M. Flack described histologically in the right atrium of different mammalian including human hearts a structure which they called sinu-auricular node and which they interpreted as the place where the heart beat originates. One year earlier K.F. Wenckebach had reported on an arrhythmia which he explained by polygraphic technique as "vein-atrial block" (today: sinoatrial block). To such an assumption he had to suppose that the heart action begins in the vena cava superior where he described a "small but interesting musculature" above the atrium as the morphological basis of the origin. Recently, with regard to the publication dates of these findings it was claimed (W. Ehrlich) that we should owe the honour of having discovered the sinus node morphologically to Wenckebach and not to Keith and Flack. Referring to the original publications it is shown that Wenckebach as well as Keith and Flack refered to different ideas. Wenckebach supposed the location of the origin of the heart beat in a macroscopically discernible muscle placed at the vena cava superior just above but separated from the right atrium. As the only connection capable of conduction between both he described a special bundle. On the contrary, Keith and Flack depicted as the place where the heart action begins a microscopically defined structur in the atrium at the junction of the vena cava superior with the sorrounding venous and atrial musculature being not separated from each other. Scientific progress corroborated the interpretation of Keith and Flack, while Wenckebach desisted only slowly from his position which, after all, proved incorrect.

Although cardiac complications are well known in myotonic dystrophy (DM), patients rarely manifest symptoms of cardiac disease, and if so they most often show conduction abnormalities or arrhythmia. In this study, specific cardiac findings were reviewed in 79 patients with DM. No correlation was found between the cardiac assessments and the CTG expansion. Thus, for a single patient the cardiac involvement in the disease can not be predicted from the findings of the genetic investigation. On the other hand, a clear positive relationship of the PR interval with the QRS duration was revealed, as well as a positive correlation between the age of the DM patient and the QRS duration, which increases with 0,54 ms/year. Systolic dysfunction, evaluated by transthoracic echocardiography, seems to be quite uncommon. In 32 % of the patients with a normal ECG, the 24 h Holter monitoring showed arrhythmias and conduction abnormalities. Based on these findings we recommend a follow up of DM patients not only based on the ECG, but also through 24 h Holter monitoring.

Ligation of the posterior interventricular branch of the right coronary artery in rats induced bradyarrhythmia similar by its pathophysiological mechanisms to bradyarrhythmias developed in humans during acute ischemia of the posterior cardiac wall. The type and severity of arrhythmia and conduction disturbances, their latency and duration, and correlation with the volume of damaged myocardial tissue were determined. The efficacy and safety of the use of methylxanthines during acute myocardial ischemia was proved.

This work is concerned with modeling the key interrelated biochemical reactions involved in initiating and inhibiting pacemaking activity in the mammalian sinoatrial node. A detailed model involving G-proteins was developed to better represent the activation pathway for adenylate cyclase. Concentration profiles of an activated G-protein complex [αTC] were established as a function of the membrane bound calcium calmodulin concentration. A previously developed model used to establish temporal profiles of cAMP was improved using the G-protein effects through the [αTC] functionality. Methods were also developed to model inhibition of G-protein by acetylcholine. Analytical solutions were developed to predict acetylcholine concentration profiles as a function of diffusion parameter and duration of acetylcholine pulses. The model was used to demonstrate suppression of cAMP by acetylcholine through G-protein pathways. It provides a basis for a tool to quantify key biochemical species during stimulation and inhibition of sinoatrial node pacemaking. A stability analysis of the model equations has potential application in studying the link between the biochemical species concentrations and abnormal effects in sinoatrial node pacemaking. © 1999 Biomedical Engineering Society. PAC99: 8710+e, 8714Ee, 8719Nn, 8719Hh, 8717Aa

A 9-year-old girl was admitted because she had had palpitations for 2 years. Her electrocardiogram revealed multifocal ectopic beats with left bundle branch morphology, sinoatrial block, and first- and second-degree atrioventricular blocks. Cross-sectional echocardiography demonstrated an enlarged left ventricle and filling defects and sacculations of the posterior left ventricular wall, apex, and septum. The diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) was confirmed by endomyocardial biopsy and thallium 201 scintigraphy. We present this case because of the rarity of left ventricular involvement associated with ARVD. We also emphasize the value of echocardiography in the early diagnosis of ARVD.

Myocardial contractility is regulated by adrenergic stimulation, the strength-length relationship and the force-frequency relationship or Bowditch effect. The latter mechanism was clearly demonstrated in muscle strips, in the isolated heart as well as in in-vivo experiments. The aim of this study was to further investigate the role of the force-frequency effect on the contractile response to exercise or isoproterenol infusion in conditions of restricted increases in heart rate i.e., AV-block, sinus node block and beta-adrenoceptor block.Nineteen dogs were instrumented with a left ventricular miniature pressure gauge, catheters in the aorta, pulmonary artery and left atrium and pacing leads on the left atrium and left ventricle. In order to control the chronotropic response during sympathetic stimulation, permanent AV-block was induced in nine dogs, sinus node block using UL-FS 49 and beta-adrenoceptor block using propranolol was studied in ten dogs.Adrenergic stimulation (isoproterenol 0.4 micro g/kg or exercise) after total AV-block failed to increase LVdP/dt. However, increasing LV pacing rate (from 50 up to 200 bpm) prior to adrenergic stimulation elicited a significant increase in LVdP/dt (4762 +/- 166 mmHg/s vs. 6485 +/- 381 mmHg/s, p0.05). In dogs in sinus rhythm, heart rate and LVdP/dt response to isoproterenol and exercise following pre-treatment with UL-FS 49 is significantly reduced, with heart rate increasing from 103 +/- 7 up to 154 +/- 5 bpm and LV dP/dt(max) from 2925 +/- 171 mmHg/s to 6249 +/- 400 mmHg/s compared to the response in control conditions (HR 220 +/- 3 bpm and LV dP/dt(max) 7473 +/- 616 mmHg/s) (p0.05). When heart rate is matched using atrial pacing, the LVdP/dt(max) response reached comparable values as observed in control conditions (7310 +/- 550 mmHg/s). Similar responses were obtained during exercise. Beta-adrenoceptor blockade attenuates considerably the heart rate and LVdP/dt response to sympathetic stimulation. Adjusting heart rate with atrial pacing restores only partially LVdP/dt(max).During sympathetic stimulation, the chronotropic response plays a major role for the concomitant full expression of the inotropic response. In conditions where increases in heart rate are absent or severely restricted such as in permanent AV-block, sinus node block and beta-adrenoceptor block, the inotropic response will also be impaired.

In the process of carrying out a routine check up examination on a group of horses of a riding school in Shiraz, a horse demonstrated frequent long pauses in heart rate of 33beats per minute on auscultation. A base apex electrocardiogram (ECG) was recorded to determine the type of conduction disturbance. At the time of ECG recording, the animal was normal with no apparent sign of any body disorders and respiratory movement and temperature were within normal range. CBC and serum biochemical analysis carried out were within normal limits of our school reference values. The horse was given a light exercise and was examined immediately after exercise and 15 minutes thereafter. The heart rate immediately after the end of exercise was 65 bpm and slowed down to 35 bpm 15 minutes after exercise with no sign of heart block.

Epicardial potentials of the sinus node, the right atrium, and the right ventricle were recorded in dogs during cold potassium-induced cardioplegia. We found that the sinus node fibers were more resistant to the cardioplegia than were the other myocardial fibers. When the cardioplegia rendered the atrial muscle inexcitable, the high frequency atrial potential was delayed and then abolished in the sinus node electrogram, and a smooth tracing similar to the action potential of the sinus node cell appeared. These findings should be pertinent for the cardiac surgeon attempting to avoid surgically-induced sinoatrial arrhythmias.