Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs. Atrial tissue was processed for analysis of Cx43 topology using immunohistochemistry, expression of Cx43 protein using immunobloting, and expression of mRNA of Cx43 and extracellular matrix metalloproteinase-2 (MMP-2) using real time PCR. Immunohistochemistry revealed uniform Cx43 distribution predominantly on lateral sides of the cardiomyocytes of young male and female GP atria. In contrast, non-uniform distribution, mislocalization and reduced immunolabeling of Cx43 were detected in atria of old GPs. In parallel, the atrial tissue levels of Cx43 mRNA were significantly decreased, while mRNA expression of MMP-2 was significantly increased in old versus young GPs. The changes were more pronounced in old GPs males comparing to females. Findings indicate that age-related down-regulation of atrial Cx43 and up-regulation of MMP-2 as well as disordered Cx43 distribution can facilitate development of AF in old guinea pig hearts., V. Nagibin, T. Egan Benova, C. Viczenczova, B. Szeiffova Bacova, I. Dovinova, M. Barancik, N. Tribulova., and Obsahuje bibliografii
Atrial fibrosis is considered as the basis in the development of long-standing atrial fibrillation (AF). However, in advanced heart failure (HF), the independent role of fibrosis for AF development is less clear since HF itself leads to atrial scarring. Our study aimed to differentiate patients with AF from patients without AF in a population consisting of patients with advanced HF. Myocardial samples from the right atrial and the left ventricular wall were obtained during he art transplantation from the explanted hearts of 21 male patients with advanced HF. Long- standing AF was present in 10 of them and the remaining 11 patients served as sinus rhythm controls. Echocardiographic and hemodynamic measurements were recorded prior to heart transplantation. Collagen volume fraction (CVF), transforming growth factor-beta (TGF- β ), and connective tissue growth factor (CTGF) expression in myocardial specimens were assessed histologically and immunohistochemically. The groups were well matched according to age (51. 9±8.8 vs. 51.3±9.3 y) and co- morbidities. The AF group had high er blood pressure in the right atrium (13.6±7.7 vs. 6.0±5.0 mmHg; p=0.02), larger left atrium diameter (56.1±7.7 vs. 50±5.1 mm; p=0.043), higher left atrium wall stress (18.1±2.1 vs. 16.1±1.7 kdynes/m 2 ; p=0.04), and longer duration of HF (5.0±2.9 vs. 2.0±1.6 y, p=0.008). There were no significant differences in CVF (p=0.12), in CTGF (p=0.60), and in TGF- β expression (p=0.66) in the atrial myocardium between the two study groups. In conclusions, in advanced HF, atrial fibrosis expressed by CVF is invariably present regardless of occurrence of AF. In addition to atrial wall fibrosis, increased wall stress might contribute to AF development in long-standing AF., B. Aldhoon, ... [et al.]., and Obsahuje seznam literatury
We have examined the changes of intercellular electrical coupling protein connexin-43 (Cx43) and of PKC-ε in heart atria of diabetic rats and/or after the treatment with triiodothyronine (T3 ). Diabetes was induced in Wistar-Kyoto rats by streptozotocin (50 mg/kg, i.v.) and atria were examined after 5 (acute stage) and 10 (chronic stage) weeks. T 3 (10 μg/100 g/day) was applied via a gastric tube for the last 10 days prior to the end of the experiments to non-diabetic and to the half of diabetic rats. Expression and phosphorylated status of Cx43, as well as expression of PKC-ε , were analyzed by Western blots using mouse monoclonal anti-Cx43 and rabbit polyclonal anti-PKC-ε antibodies. We found that the Cx43 expression was significantly increased after the treatment with T3 and in the acute diabetes. Both in diabetes and after T3 treatment the phosphorylation of Cx43 isoforms was markedly suppressed compared to the non-diabetic and T3-untreated controls. Such a down-regulation was less pronounced in diabetic rats after the T3-treatment. The expression of atrial PKC-ε was increased in diabetic rats. This increase was suppressed after T3 administration and the expression was decreased in T3-treated non-diabetic rats. We suggest that the reduced Cx43 phosphorylation in diabetic and hyperthyroid rats can deteriorate a cell-to-cell coupling and consequently facilitate a development of atrial tachyarrhythmia in diabetic or hyperthyroid animals., M. Mitašíková ... [et al.]., and Obsahuje seznam literatury
Spontaneous depolarization similar to that from the sinus node was documented from the myocardial sleeves of pulmonary veins (PV) after isolation procedures. It was then hypothesized that sinus node-like tissue is present in the PVs of humans. Based on a number of features, the myocar dium of myocardial sleeves (MS) is highly arrhythmogenic. Membrane potentials originating from MS are invariably recordable at the PVs ostia in patients with atrial fibrillation (AF) and delayed conduction around the PVs ostia may play a role in re-e ntry process responsible for the initiation and maintenance of AF. Diagnostic and therapeutic evidence of premature atrial beats induced in MS of PVs and resulting in launch of AF was detected by 3D electroanatomic method of monophasic action potential (MAP). MAP recording plays an important role in a di rect view of human myocardial electrophysiology under both physiological and pathological conditions. Its crucial importance lies in the fact that it enables the study of the action potential of myocardial cell in vivo and, therefore, the study of the dynamic relation of this potential with all the organism variables. The knowledge of pathological MAPs from PV myocardial sleeves can help us to confirm a diagnosis when finding the similar action potential morphology. MAP can be also used to evaluate the therap eutic efficiency of vagal nerves suppression, radiofrequency ablation or other treatment procedures in PVs myocardial sleeves as well as for post- treatment following up., O. Kittnar, S.-G. Yang, M. Mlček., and Obsahuje bibliografii a bibliografické odkazy
Although atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, precise mechanisms that lead to the onset and persistence of AF have not completely been elucidated. Over the last decade, outstanding progress has been made in understanding the complex pathophysiology of AF. The key role of ectopic foci in pulmonary veins as a trigger of AF has been recognized. Furthermore, structural remodeling was identified as the main mechanism for AF persistence, confirming predominant role of atrial fibrosis. Systemic inflammatory state, oxidative stress injury, autonomic balance and neurohormonal activation were discerned as important modifiers that affect AF susceptibility. This new understanding of AF pathophysiology has led to the emergence of novel therapies. Ablative interventions, renin-angiotensin system blockade, modulation of oxidative stress and targeting tissue fibrosis represent new approaches in tackling AF. This review aims to provide a brief summary of novel insights into AF mechanisms and consequent therapeutic strategies., B. Aldhoon ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Beside heart failure and metabolic syndrome, atrial fibrillation is termed the cardiovascular epidemic of the 21st century. Its increased morbidity and mortality is alarming. The present, most effective therapy of atrial fibrillation is catheter ablation. Successful ablation of atrial fibrillation prevents the occurrence and progression of electrical, structural and mechanic myocardium remodelling, improves function of the left ventricle, and prevents the risk of thrombembolism. Onset of sinus rhythm activates the reversal remodelling leading to wall reconstruction and atrium reduction. The paper reviews the technique and presents own experience with catheter ablation., R. Lábrová, J. Špinar, N. Honzíková., and Obsahuje bibliografii a bibliografické odkazy