Association of Single Nucleotide Polymorphisms with Atrial Fibrillation and the Outcome after Catheter Ablation.

BACKGROUND: The association of gene variants with atrial fibrillation (AF) type and the recurrence of AF after catheter ablation in Taiwan is still unclear. In this study, we aimed to investigate the relationships between gene variants, AF type, and the recurrence of AF. METHODS: In our investigation, we examined 383 consecutive patients with AF (61.9 ± 14.0 years; 63% men); of these 383 patients, 189 underwent catheter ablation for drug-refractory AF. Thereafter, the single nucleotide polymorphisms rs2200733, and rs7193343 were genotyped using real-time polymerase chain reaction. RESULTS: The rs7193343 variant was independently associated with non-paroxysmal AF (non-PAF). In the PAF group, the rs7193343 variant was independently associated with AF recurrence after catheter ablation. However, the rs2200733 variant was not associated with AF recurrence in this group. The combination of the rs7193343 and rs2200733 risk alleles was associated with a better predictive power in the PAF patients. In contrast, in the non-PAF group, the SNPs were not associated with recurrence. The rs7193343 and rs2200733 variants were not associated with different atrial voltage and activation times. CONCLUSIONS: The rs7193343 variants were associated with AF recurrence after catheter ablation in PAF patients but not in non-PAF patients. The rs7193343 CC variant was independently associated with non-PAF.

Differential effects of central and peripheral fat tissues on the delayed rectifier K(+) outward currents in cardiac myocytes.

OBJECTIVES: The amount of fat tissue is associated with an increasing incidence of cardiac arrhythmias. The purpose of this study was to investigate effects of adipocytokines from different body fat on delayed rectifier K(+) outward currents (IK). METHODS: H9c2 cells were treated with adipocytokine-free medium (the Adipo-free group) and with adipocytokines from epicardial (central fat group) and limb (peripheral fat group) rat fat tissues. IK, as well as expressions of Kv2.1 and Kv2.1 mRNA in H9c2 cells, were measured and compared between different groups. RESULTS: IK measured in H9c2 cells immediately after treatment with adipocytokines were not significantly different from those treated with adipocytokine-free medium. After H9c2 cells were treated with adipocytokines for 18 h, IK were significantly decreased in the peripheral and central fat groups in comparison with the Adipo-free group. Compared with the peripheral fat group, IK were more significantly decreased in the central fat group. Expressions of Kv2.1 and Kv2.1 mRNA in H9c2 cells were not significantly different among the three groups. CONCLUSIONS: Adipocytokines significantly decreased IK in H9c2 cells, and IK was more prominently decreased by adipocytokines from epicardial fat than from limb fat tissues. The decrease in IK by adipocytokines may partially contribute to the mechanisms of arrhythmogenesis by fat tissues.

Characteristics of atrial substrates for atrial tachyarrhythmias induced in aged and hypercholesterolemic rabbits.

BACKGROUND: Old age and dyslipidemia increase the occurrence of atrial tachyarrhythmias (ATR). This study investigated the effect of age and hypercholesterolemia on the atrial substrates for ATR. METHODS: Five 3-year-old rabbits fed standard chow were categorized into an old-age group, five 3-month-old rabbits fed high cholesterol chow were used as a hypercholesterolemia group, and five 3-month-old rabbits fed standard chow were controls. Effective refractory period, atrial vulnerability to ATR, expressions of connexin40 (Cx40) and connexin43 (Cx43), phosphorylated c-Jun N-terminal Kinase (P-JNK), and degree of fibrosis in the right (RA) and left (LA) atria were compared. RESULTS: Old-age and hypercholesterolemia rabbits were more vulnerable to ATR than the controls (18,628 ± 13,981 ms and 30,157 ± 39,548 ms vs 639 ± 325 ms, P < 0.05). Old-age rabbits had significantly decreased Cx40 expression in both atria (3.9-fold decrease in RA, P < 0.01 and 4.8-fold in LA, P < 0.01) and significantly decreased Cx43 in RA (14-fold, P < 0.01). Hypercholesterolemia rabbits had significantly decreased Cx40 expression in both atrial (18-fold decrease in RA, P < 0.01 and 17-fold in LA, P < 0.01) and significantly increased Cx43 expression in LA (five-fold increase, P < 0.01). Hypercholesterolemia, but not old-age rabbits, had greater expression of P-JNK in both atria (1.8-fold in RA and 2.3-fold in LA, P < 0.01). There were no significant group differences in ERP or degree of atrial fibrosis in both atria. CONCLUSIONS: ATR is more easily induced in the atria of old-age and hypercholesterolemia rabbits than younger rabbits with normal cholesterol levels. The age and hypercholesterolemia induced changes in gap junctions expression may have partially contributed to the higher atrial vulnerability to ATR.

Zebrafish Model-Based Assessment of Indoxyl Sulfate-Induced Oxidative Stress and Its Impact on Renal and Cardiac Development.

Kidney disease patients may have concurrent chronic kidney disease-associated mineral bone disorder and hypertension. Cardiovascular disease (CVD) and neuropathy occur due to kidney failure-induced accumulation of uremic toxins in the body. Indoxyl sulfate (IS), a product of indole metabolism in the liver, is produced from tryptophan by the intestinal flora and is ultimately excreted through the kidneys. Hemodialysis helps renal failure patients eliminate many nephrotoxins, except for IS, which leads to a poor prognosis. Although the impacts of IS on cardiac and renal development have been well documented using mouse and rat models, other model organisms, such as zebrafish, have rarely been studied. The zebrafish genome shares at least 70% similarity with the human genome; therefore, zebrafish are ideal model organisms for studying vertebrate development, including renal development. In this study, we aimed to investigate the impact of IS on the development of zebrafish embryos, especially cardiac and renal development. At 24 h postfertilization (hpf), zebrafish were exposed to IS at concentrations ranging from 2.5 to 10 mM. IS reduced survival and the hatching rate, caused cardiac edema, increased mortality, and shortened the body length of zebrafish embryos. In addition, IS decreased heart rates and renal function. IS affected zebrafish development via the ROS and MAPK pathways, which subsequently led to inflammation in the embryos. The results suggest that IS interferes with cardiac and renal development in zebrafish embryos, providing new evidence about the toxicity of IS to aquatic organisms and new insights for the assessment of human health risks. Accordingly, we suggest that zebrafish studies can ideally complement mouse model studies to allow the simultaneous and comprehensive investigation of the physiological impacts of uremic endotheliotoxins, such as IS, on cardiac and renal development.