Ventricular response as a predictor of the termination of sustained paroxysmal atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. Accurate detection of the timing and possibility of AF termination is vital for optimizing rhythm and rate control strategies. The present study evaluated whether the ventricular response (VR) in AF offers a distinctive electrocardiographic indicator for predicting AF termination. METHODS: Patients experiencing sustained paroxysmal AF for more than 3 h were observed using 24-h ambulatory Holter monitoring. VR within 5 min before AF termination (VR 0-5 min, BAFT) was compared with VR observed during the 60th to 65th min (VR 60-65 min, BAFT) and the 120th to 125th min (VR 120-125 min, BAFT) before AF termination. Maximum and minimum VRs were calculated on the basis of the average of the highest and lowest VRs across 10 consecutive heartbeats. RESULTS: Data from 37 episodes of paroxysmal AF revealed that the minimum VR0-5 min, BAFT (64 ± 20 bpm) was significantly faster than both the minimum VR120-125 min, BAFT (56 ± 15 bpm) and the minimum VR60-65 min, BAFT (57 ± 16 bpm, p < .05). Similarly, the maximum VR0-5 min, BAFT (158 ± 49 bpm) was significantly faster than the maximum VR120-125 min, BAFT (148 ± 45 bpm, p < .05). In the daytime, the minimum VR0-5 min, BAFT (66 ± 20 bpm) was significantly faster than both the minimum VR60-65 min, BAFT (58 ± 17 bpm) and minimum VR120-125 min, BAFT (57 ± 15 bpm, p < .05). However, the mean and maximum VR0-5 min, BAFT in the daytime were similar to the mean and maximum VR120-125 min in the daytime, respectively. At night, the minimum, mean, and maximum VR0-5 min, BAFT were similar to the minimum, mean, and maximum VR120-125 min, respectively. CONCLUSIONS: Elevated VR rates during AF episodes may be predictors for the termination of AF, especially during the daytime and in patients with nondilated left atria. These findings may guide the development of clinical approaches to rhythm control in AF.

Effects of phosphodiesterase-1 inhibitor on pulmonary vein electrophysiology and arrhythmogenesis.

INTRODUCTION: Phosphodiesterase (PDE) isoform inhibitors have mechanical and electrical effects on the heart. Inhibition of PDE-1 enzymes is a novel strategy for treating heart failure. However, the electrophysiological effects of PDE-1 inhibition on the heart remain unclear. This study explored the effects of PDE-1 inhibition using ITI-214 on electrical activity in the pulmonary vein (PV), the most common trigger of atrial fibrillation, and investigated the underlying ionic mechanisms. METHODS: Conventional microelectrodes or whole-cell patch clamps were employed to study the effects of ITI-214 (0.1-10 µM) on PV electrical activity, mechanical responses and ionic currents in isolated rabbit PV tissue specimens and isolated single PV cardiomyocytes. RESULTS: ITI-214 at 1 µM and 10 µM (but not 0.1 µM) significantly reduced PV spontaneous beating rate (10 ± 2% and 10 ± 3%, respectively) and PV diastolic tension (11 ± 3% and 17 ± 3%, respectively). ITI-24 (1 µM) significantly reduced late sodium current (INa-Late ), L-type calcium current (ICa-L ) and the reverse mode of the sodium-calcium exchanger (NCX), but it did not affect peak sodium currents. CONCLUSIONS: ITI-214 reduces PV spontaneous activity and PV diastolic tension by reducing INa-Late , ICa-L and NCX current. Considering its therapeutic potential in heart failure, targeting PDE-1 inhibition may provide a novel strategy for managing atrial arrhythmogenesis.

Circulating level of microRNA-142-5p is a potential biomarker for predicting in-stent restenosis: a case-control study.

BACKGROUND: Patients who receive percutaneous coronary intervention (PCI) have different chances of developing in-stent restenosis (ISR). To date, no predictable biomarker can be applied in the clinic. MicroRNAs (miRNAs or miRs) play critical roles in transcription regulation, and their circulating levels were reported to have potential as clinical biomarkers. METHODS: In total, 93 coronary stent-implanted patients without pregnancy, liver or renal dysfunction, malignancy, hemophilia, or autoimmune diseases were recruited in this clinical study. All recruited participants were divided into an ISR group (n = 45) and a non-ISR group (n = 48) based on their restenotic status as confirmed by cardiologists at the first follow-up visit (6 months after surgery). Blood samples of all participants were harvested to measure circulating levels of miRNA candidates (miR-132, miR-142-5p, miR-15b, miR-24-2, and miR-424) to evaluate whether these circulating miRNAs can be applied as predictive biomarkers of ISR. RESULTS: Our data indicated that circulating levels of miR-142-5p were significantly higher in the ISR population, and results from the receiver operating characteristic (ROC) curve analysis also demonstrated superior discriminatory ability of miR-142-5p in predicting patients' restenotic status. In addition, circulating levels of miR-15b, miR-24-2, and miR-424 had differential expressions in participants with diabetes, hyperlipidemia, and hypertension, respectively. CONCLUSIONS: The current study revealed that the circulating level of miR-142-5p has potential application as a clinical biomarker for predicting the development of ISR in stent-implanted patients.

The AMP-activated protein kinase modulates hypothermia-induced J wave.

BACKGROUND: The mechanism underlying the occurrence of the J wave in low temperature remains unclear. However, low temperature is associated with metabolic disorder and 5' AMP-activated protein kinase (AMPK), which modulates ionic currents and cardiac metabolism. This study investigated whether AMPK regulation can modulate the occurrence of the J wave at low temperature. METHODS: Unipolar and bipolar leads were used to record monophasic action potential (the endocardium and epicardium) and pseudo-electrocardiograms (inferior leads) to study the cardiac electrical activity. Measurements were taken in isolated Langendorff rabbit hearts at both 30℃ and 37℃ before and after administration of 4-aminopyridine (an ultrarapid delayed rectifier potassium current inhibitor, IKur , 50 µmol L-1 ), PF06409577 (an AMPK activator, 1 µmol L-1 ), compound C (an AMPK inhibitor, 10 µmol L-1 ) and glibenclamide (an ATP-sensitive inward rectifier potassium channel inhibitor, IKATP , 20 µmol L-1 ). RESULTS: The amplitude of the J wave (2.46 ± 0.34 mV vs. 1.11 ± 0.23 mV, P < .01) at 30℃ (n = 15) was larger than that at 37℃ (n = 15). PF06409577 (1 µmol L-1 ) increased the J waves at both 30℃ and 37℃. In contrast, compound C (10 µmol L-1 ) reduced J wave at both 37℃ and 30℃. Low-temperature-induced J waves were individually suppressed by 4-AP (50 µmol L-1 ) and glibenclamide (20 µmol L-1 ). CONCLUSIONS: AMPK inhibition reduces low-temperature-induced J waves and possible ventricular arrhythmogenesis by modulating IKATP and IKur channels.

Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes.

BACKGROUND: Atrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. However, the role of AVP in HF-induced AF still remains unclear. Pulmonary veins (PVs) are central in the genesis of AF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms. METHODS: Patch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, Ca2+ homeostasis, and Ca2+ regulatory proteins in isolated rabbit single PV cardiomyocytes incubated with and without AVP (1 µM), OPC 21268 (0.1 µM, AVP V1 antagonist), or OPC 41061 (10 nM, AVP V2 antagonist) for 4-6 h. RESULTS: AVP (0.1 and 1 µM)-treated PV cardiomyocytes had a faster beating rate (108 to 152%) than the control cells. AVP (1 µM) treated PV cardiomyocytes had higher late sodium (Na+) and Na+/Ca2+ exchanger (NCX) currents than control PV cardiomyocytes. AVP (1 µM) treated PV cardiomyocytes had smaller Ca2+i transients, and sarcoplasmic reticulum (SR) Ca2+ content as well as higher Ca2+ leak. However, combined AVP (1 µM) and OPC 21268 (0.1 µM) treated PV cardiomyocytes had a slower PV beating rate, larger Ca2+i transients and SR Ca2+ content, smaller late Na+ and NCX currents than AVP (1 µM)-treated PV cardiomyocytes. Western blot experiments showed that AVP (1 µM) treated PV cardiomyocytes had higher expression of NCX and p-CaMKII, and a higher ratio of p-CaMKII/CaMKII. CONCLUSIONS: AVP increases PV arrhythmogenesis with dysregulated Ca2+ homeostasis through vasopressin V1 signaling.

Levosimendan differentially modulates electrophysiological activities of sinoatrial nodes, pulmonary veins, and the left and right atria.

INTRODUCTION: Calcium overload increases the risk of atrial fibrillation (AF). Levosimendan, a calcium sensitizer, increases myofilament contractility. Clinical reports suggested that levosimendan might increase AF occurrence, but the electrophysiological effects of levosimendan on AF substrates and triggers (pulmonary veins, PVs) are not clear. METHODS AND RESULTS: Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial nodes (SANs), the left atrium (LA), and right atrium (RA) before and after application of different concentrations of levosimendan with or without milrinone (a phosphodiesterase [PDE] III inhibitor), and glibenclamide (an ATP-sensitive potassium channel [KATP ] inhibitor). Levosimendan (0.03, 0.1, 0.3, and 1 µM) significantly increased spontaneous rates from 2.1 ± 0.2 to 2.5 ± 0.2, 2.5 ± 0.2, 2.5 ± 0.1, and 2.7 ± 0.2 Hz, respectively, in PVs (n = 10), but had no effects on denudated PVs (n = 9). Additionally, levosimendan significantly induced burst firing and/or triggered beats in intact PVs, but not in denudated PVs. In contrast, levosimendan at 0.3 and 1 µM increased the SAN spontaneous rate. In the presence of milrinone (10 µM), levosimendan (1 µM) did not increase the PV spontaneous activity. Moreover, glibenclamide (100 µM) prevented acceleration of the levosimendan-induced SAN and PV rates. In the LA, levosimendan at 0.3 and 1 µM shortened the AP duration, and increased contractility at 0.03, 0.1, 0.3, and 1 µM. In contrast, levosimendan did not change the RA contractility, and shortened the AP duration only at 1 µM. CONCLUSIONS: Levosimendan increased PV arrhythmogenesis through activating endothelial PDE III and the KATP , and modulating PV tension.

Modulation of Autonomic Nervous Activity in the Termination of Paroxysmal Atrial Fibrillation.

BACKGROUND: Autonomic nervous activity plays a critical role in the genesis of paroxysmal atrial fibrillation (AF, PAF). However, the role of autonomic nervous activity on AF termination has not been elucidated. Heart rate variability (HRV) is widely used to evaluate autonomic nervous activity in humans. The purpose of this study was to assess whether autonomic nervous activity assessed by HRV contributes to AF termination. METHODS: Electrocardiograms (ECGs) and HRV were studied in patients with termination of sustained (>30 s) PAF by 24-hour ambulatory Holter monitoring. The 20-minute interval after termination of AF was divided into four segments of 5 minutes each, and a frequency analysis was applied to each 5-minute segment. RESULTS: In 52 AF episodes, the ultra-low-frequency power, very-low-frequency power, low-frequency power (LF), high-frequency power (HF), and total power significantly decreased with time after episodes of AF termination. The LF/HF (L/H) ratio, normalized LF (LFnu), and normalized HF (HFnu) significantly changed after AF termination. Eighteen (35%) episodes had decreased LFnu and increased HFnu (sympathetic withdrawal and vagal activation), which had slower average AF ventricular responses (92 ± 16 beats/min vs 105 ± 24 beats/min, P < 0.05) than the AF termination episodes (n = 34, 65%) with increased LFnu and decreased HFnu (sympathetic activation and vagal withdrawal). Moreover, older patients (aged >65 years) had a higher incidence (n = 27, 75%) of AF termination with increased LFnu and decreased HFnu than did younger patients (aged ≤65 years, n = 7, 44%, P < 0.05). CONCLUSION: Autonomic changes critically regulate termination of PAF, which is modulated by aging.

Pericardial Fat Is Associated With the Risk of Ventricular Arrhythmia in Asian Patients.

BACKGROUND: Pericardial fat is correlated with the occurrence of atrial fibrillation or coronary atherosclerosis. However, the role of pericardial fat in ventricular arrhythmia remains unclear. METHODS AND RESULTS: Patients who had undergone dual-source computed tomography and 24-h Holter ECG were retrospectively enrolled. Quantification of the volume of pericardial fat surrounding the ventricles was analyzed using threshold attenuation of dual-source CT. The volume of pericardial fat was significantly different among those without ventricular premature beats (VPBs) in 24 h (n=28), those with occasional VPBs (n=54) and those with frequent VPBs (n=34) (12.5±6.1 cm(3)vs. 14±8.9 cm(3)vs. 29.9±17.3 cm(3), P<0.001). In addition, the number of VPBs strongly correlated with the volume of total pericardial fat (R=0.501, P<0.001), right ventricular (RV) pericardial fat (R=0.539, P<0.001), and left ventricular pericardial fat (R=0.376, P<0.001). Multivariate logistic regression analysis showed that quartiles of RV localized pericardial fat significantly increased the risk of frequent VPBs (OR=3.2, P=0.047). Moreover, the number of VPBs in 24 h was significantly different among the patients with a fat volume within the 25th percentile, 25-75th percentile and 75th percentile. CONCLUSIONS: Pericardial fat (especially RV pericardial fat) was associated with the frequency of VPBs, which suggests the arrhythmogenic potential of ventricular pericardial fat. (Circ J 2016; 80: 1726-1733).

Distinctive electrophysiological characteristics of right ventricular out-flow tract cardiomyocytes.

Ventricular arrhythmias commonly originate from the right ventricular out-flow tract (RVOT). However, the electrophysiological characteristics and Ca(2+) homoeostasis of RVOT cardiomyocytes remain unclear. Whole-cell patch clamp and indo-1 fluorometric ratio techniques were used to investigate action potentials, Ca(2+) homoeostasis and ionic currents in isolated cardiomyocytes from the rabbit RVOT and right ventricular apex (RVA). Conventional microelectrodes were used to record the electrical activity before and after (KN-93, a Ca(2+) /calmodulin-dependent kinase II inhibitor, or ranolazine, a late sodium current inhibitor) treatment in RVOT and RVA tissue preparations under electrical pacing and ouabain (Na(+) /K(+) ATPase inhibitor) administration. In contrast to RVA cardiomyocytes, RVOT cardiomyocytes were characterized by longer action potential duration measured at 90% and 50% repolarization, larger Ca(2+) transients, higher Ca(2+) stores, higher late Na(+) and transient outward K(+) currents, but smaller delayed rectifier K(+) , L-type Ca(2+) currents and Na(+) -Ca(2+) exchanger currents. RVOT cardiomyocytes showed significantly more pacing-induced delayed afterdepolarizations (22% versus 0%, P < 0.05) and ouabain-induced ventricular arrhythmias (94% versus 61%, P < 0.05) than RVA cardiomyocytes. Consistently, it took longer time (9 ± 1 versus 4 ± 1 min., P < 0.05) to eliminate ouabain-induced ventricular arrhythmias after application of KN-93 (but not ranolazine) in the RVOT in comparison with the RVA. These results indicate that RVOT cardiomyocytes have distinct electrophysiological characteristics with longer AP duration and greater Ca(2+) content, which could contribute to the high RVOT arrhythmogenic activity.

Electromechanical effects of 1,25-dihydroxyvitamin d with antiatrial fibrillation activities.

INTRODUCTION: Treatment with 1,25-dihydroxyvitamin D (1,25[OH]2 D) has several cardiovascular benefits. 1,25[OH]2 D has direct cellular effects, but its effects on the atrium are not clear. We evaluated the effects of 1,25[OH]2 D on the atrial electrophysiology and atrial fibrillation (AF). METHODS: Conventional microelectrodes were used to record action potentials (APs) and contractility in isolated rabbit left atrium (LA) tissue preparations before and after the administration of 0.01, 0.1, and 1 nM 1,25[OH]2 D with and without rapid atrial pacing (RAP) and acetylcholine (5 mM)-induced AF. Surface ECG and intracardiac electrograms were recorded before and after the intravenous administration of 4 units/kg of 1,25[OH]2 D in heart failure (HF) rabbits (4 weeks after coronary artery ligation) with RAP and acetylcholine-induced AF. RESULTS: 1,25[OH]2 D dose-dependently increased the AP duration in the LA, which was abolished by pretreatment with 0.1 µM ryanodine. RAP and 5 mM acetylcholine-induced fewer (64.3% vs 100%, P < 0.05) AF occurrences in the presence (n = 14) of 1,25[OH]2 D than those (n = 14) in the absence of 1,25[OH]2 D. The LA treated with 1,25[OH]2 D (n = 9) had a slower maximal AF rate (10.9 ± 2.4 Hz vs 13.3 ± 2.7 Hz, P < 0.05) than the LA (n = 14) without 1,25[OH]2 D. Moreover, 1,25[OH]2 D caused a lower AF inducible percentage (11.0 ± 1.9% vs 100 ± 0%, P < 0.001) and a shorter duration (4 ± 0.4 seconds vs 309 ± 26 seconds, P < 0.001) with a prolonged LA 90% monophasic AP duration (94.1 ± 0.2 milliseconds vs 98.5 ± 0.1 milliseconds, P < 0.05) in 5 rabbits with HF. 1,25[OH]2 D did not prolong the QT interval or 90% of the AP duration in isolated Purkinje fibers. CONCLUSION: 1,25[OH]2 D has direct electromechanical effects on the LA and can prevent or terminate AF.

Gender modulates the aging effects on different patterns of early repolarization.

Distinct patterns of early repolarization (ER) are associated with ventricular fibrillation and arrhythmic death. We evaluated whether gender modulated the aging effects on different ER patterns. We studied manifestations of ER in the anterior, inferior, and lateral leads on standard 12-lead electrocardiography from male (n = 1077) and female (n = 1170) individuals of young (≤44 years), middle-aged (45-64 years), and elderly (≥65 years) subjects. Among a total of 2247 individuals, 543 (24.2 %) subjects had ER and 417 (18.6 %) had single-location ER. Single-location ER occurred less in lateral leads than in anterior or inferior leads (2.1, 7.8, 8.6 %, respectively, p < 0.05). Subjects with inferior ER (n = 193) were older (61 ± 14, 49 ± 14, 54 ± 16 years, respectively, p < 0.05) than those with anterior (n = 176) or lateral (n = 48) ER. In males with ER, the elderly group (n = 22) had fewer instances of anterior ER (34, 59, 80 %, respectively, p < 0.05) than middle-aged (n = 76) or young (n = 59) groups. Elderly males (n = 37) and females (n = 48) had greater instances of inferior ER (57, 32, 19 %, p < 0.05; 86, 62, 46 %, respectively, p < 0.05) than middle-aged males (n = 41) and females (n = 41), and young males (n = 14) and females (n = 12), respectively. In conclusion, gender modulates the aging effects on the occurrences of anterior ER and inferior ER.

CHA2DS2-VASc Score and Heart Rate Predict Ischemic Stroke Outcomes in Patients withAtrial Fibrillation.

PURPOSE: To evaluate the factors determining the severity and outcome of ischemic stroke in patients with atrial fibrillation (AF). METHODS: Our study examined 210 patients with AF and acute ischemic stroke to investigate the relative risks of age, gender, comorbidities, CHADS2 and CHA2DS2-VASc scores, warfarin use, heart rate, and blood pressure on stroke severity, hospitalization duration, and mortality rate. RESULTS: Patients with poor outcomes [n = 109, National Institutes of Health Stroke Scale (NIHSS) scores of ≥ 8] had elevated CHA2DS2-VASc scores [5, interquartile range (IQR) 3-6 versus 4, IQR 2.5-5, p = 0.005] and were older with a female predominance, less prior warfarin use, and a higher heart rate (93 ± 24 versus 84 ± 20 beats/min, p = 0.004) in the emergency department, with a longer duration of hospitalization (24 ± 23 versus 11 ± 12 days, p < 0.001) and a higher mortality rate (11.0% versus 0.0%, p = 0.002) than those with better outcomes (n = 101, low NIHSS scores of ≤ 7). Patients who died (n = 12) were older and had a higher NIHSS, CHADS2 (3.5, IQR 2-4.75 versus 2, IQR 1-4, p = 0.040), or CHA2DS2-VASc (5.5, IQR 4-6 versus 4, IQR 3-5, p = 0.046) scores than patients who survived. The multivariate analysis showed that female gender, no prior warfarin use, and heart rate were independent predictors of stroke severity. CONCLUSIONS: Our results showed that CHADS2 and CHA2DS2-VASc scores, and heart rate were useful parameters for predicting outcomes in AF patients with stroke. KEY WORDS: Atrial fibrillation; CHA2DS2-VASc score; Heart rate; Ischemic stroke.

Bipolar Disorder and Schizophrenia Present Different Risks of Atrial fibrillation: A Nationwide Population-Based Analysis.

BACKGROUND: Atrial fibrillation (AF) is increasingly prevalent in society, and can elevate cardiac morbidity and mortality. Psychosis and gender are known to play important roles in the genesis of AF. However, it is not clear whether gender modulates the impact of different psychoses on the occurrences of AF. METHODS: We identified patients suffering from bipolar disorder and schizophrenia, with and without AF, using the Taiwan National Health Insurance nationwide database. The identified patient population consisted of 927,915 subjects (463,050 males and 464,865 females) from 2001 to 2008, which included 2,963 (3.2 ‰) schizophrenia patients (1,650 males and 1,313 females) and 5,112 (5.5 ‰) bipolar-disorder patients (1,934 males and 3,178 females). RESULTS: The male and female bipolar-disorder patients had higher prevalences of AF than did male (16.5 ‰ vs. 2.4 ‰, p < 0.001) and female (12.9 ‰ vs. 2.3 ‰, p < 0.001) schizophrenia patients. Furthermore, male and female bipolar-disorder patients had higher AF prevalences than did males (8.5 ‰, p < 0.001) and females (7.2 ‰, p < 0.001) in the general population. Schizophrenia patients had lower AF prevalence than the general population in male, but not in female gender. Males had a higher AF prevalence than females. However, male and female bipolar disorder and schizophrenia patients had similar AF prevalences. Those patients with schizophrenia and bipolar-disorder patients with AF were older than those without AF. CONCLUSIONS: Differing risk factors for AF were identified in bipolar-disorder and schizophrenia patients. Compared to the general population, gender may have different impacts on the occurrence of AF in psychosis patients. KEY WORDS: Atrial fibrillation; Bipolar disorder; Population-based study; Schizophrenia.

Adverse Cardiovascular Effects of COVID-19 Vaccination: A Systematic Review.

Several vaccines against coronavirus disease 2019 (COVID-19)-caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-have been developed since the COVID-19 pandemic began. Of these, 7 have been approved in the World Health Organization's Emergency Use Listing. However, these vaccines have been reported to have rare or serious adverse cardiovascular effects. This review presents updated information on the adverse cardiovascular effects of the approved COVID-19 vaccines-including inactivated vaccines, protein subunit vaccines, virus-like particles, nucleic acid vaccines, and viral vector vaccines-and the underlying mechanisms.

Apamin modulates electrophysiological characteristics of the pulmonary vein and the Sinoatrial Node.

BACKGROUND: Small-conductance calcium-activated potassium (SK) channels play an important role in atrial electrophysiology. Blocking SK channels prolongs action potential (AP) duration and attenuate electrical remodelling. The effects of SK blocking on the pulmonary vein (PV) and the sinoatrial node (SAN) remain unclear. MATERIALS AND METHODS: Conventional microelectrodes were used to record the AP in SANs and in isolated rabbit PVs with and without denudation before and after treatment with apamin (1, 10 nM). Using the whole-cell patch-clamp technique, the SK current was investigated in isolated single PV and SAN myocytes. RESULTS: In nondenudated PVs (n = 6), apamin (1 and 10 nM) increased PV spontaneous activity (from 1.8 ± 0.2 Hz to 2.4 ± 0.2 Hz and 2.3 ± 0.2 Hz, P < 0.05) and increased the PV tension by 42 ± 14% and 37 ± 11%. Conversely, in denudated PVs (n = 6), apamin (1 and 10 nM) decreased spontaneous activity (from 2.2 ± 0.3 Hz to 1.9 ± 0.2 Hz and 1.8 ± 0.2 Hz, P < 0.05) and prolonged AP duration without changing PV tensions. Additionally, apamin (1 and 10 nM) decreased spontaneous activity (from 2.8 ± 0.1 Hz to 2.4 ± 0.1 Hz, and 2.4 ± 0.1 Hz, P < 0.05) and prolonged AP duration in SAN (n = 6). SAN myocytes had larger SK currents than did PV cardiomyocytes. Treatment with apamin (10 nM) resulted in a greater decrease (25 ± 8 vs. 20 ± 13%, P < 0.05) in spontaneous activity in isolated single SAN (n = 17) vs. PV cardiomyocytes (n = 16). CONCLUSION: Small-conductance calcium-activated potassium channels play a key role in SAN and PV spontaneous activity and AP morphology. Apamin may modulate PV electrical activity with and without endothelium dependence.

Rivaroxaban modulates electrical and mechanical characteristics of left atrium.

BACKGROUND: Rivaroxaban reduces stroke in patients with atrial fibrillation (AF). Left atrium (LA) plays a critical role in the pathophysiology of AF. However, the electromechanical effects of rivaroxaban on LA are not clear. RESULTS: Conventional microelectrodes and a whole-cell patch-clamp were used to record the action potentials (APs) and ionic currents in rabbit LA preparations and isolated single LA cardiomyocytes before and after the administration of rivaroxaban. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently reduced LA (n=7) AP durations at 90% repolarization (APD90) from 76±2 to 79±3, 67±4 (P<0.05, vs. control), 59±5, (P<0.01, vs. control), and 56±4 ms (P<0.005, vs. control), respectively. Rivaroxaban (10, 30, 100, and 300 nM) concentration-dependently increased the LA (n=7) diastolic tension by 351±69 (P<0.05, vs. control), 563±136 (P<0.05, vs. control), 582±119 (P<0.05, vs. control), and 603±108 mg (P<0.005, vs. control), respectively, but did not change LA contractility. In the presence of L-NAME (100 µM) and indomethacin (10 µM), additional rivaroxaban (300 nM) treatment did not significantly further increase the LA (n=7) diastolic tension, but shortened the APD90 from 73±2 to 60±6 ms (P<0.05, vs. control). Rivaroxaban (100 nM) increased the L-type calcium current and ultra-rapid delayed rectifier potassium current, but did not change the transient outward potassium current in isolated LA cardiomyocytes. CONCLUSIONS: Rivaroxaban modulates LA electrical and mechanical characteristics with direct ionic current effects.

Leptin modulates electrophysiological characteristics and isoproterenol-induced arrhythmogenesis in atrial myocytes.

BACKGROUND: Obesity is an important risk factor for atrial fibrillation (AF). Leptin is an important adipokine. However, it is not clear whether leptin directly modulates the electrophysiological characteristics of atrial myocytes. RESULTS: Whole cell patch clamp and indo-1 fluorescence were used to record the action potentials (APs) and ionic currents in isolated rabbit left atrial (LA) myocytes incubated with and without (control) leptin (100 nM) for 1 h to investigate the role of leptin on atrial electrophysiology. Leptin-treated LA myocytes (n = 19) had longer 20% of AP duration (28 ± 3 vs. 21 ± 2 ms, p < 0.05), but similar 50% of AP duration (51 ± 4 vs. 50 ± 3 ms, p > 0.05), and 90% of AP duration (89 ± 5 vs. 94 ± 4 ms, p > 0.05), as compared to the control (n = 22). In the presence of isoproterenol (10 nM), leptin-treated LA myocytes (n = 21) showed a lower incidence (19% vs. 54.2%, p < 0.05) of delayed afterdepolarization (DAD) than the control (n = 24). Leptin-treated LA myocytes showed a larger sodium current, but a smaller ultra-rapid delayed rectifier potassium current, and sodium-calcium exchanger current than the control. Leptin-treated and control LA myocytes exhibited a similar late sodium current, inward rectifier potassium current, transient outward current and L-type calcium current. In addition, the leptin-treated LA myocytes (n = 38) exhibited a smaller intracellular Ca2+ transient (0.21 ± 0.01 vs. 0.26 ± 0.01 R410/485, p < 0.05) and sarcoplasmic reticulum Ca2+ content (0.35 ± 0.02 vs. 0.43 ± 0.03 R410/485, p < 0.05) than the control LA myocytes (n = 42). CONCLUSIONS: Leptin regulates the LA electrophysiological characteristics and attenuates isoproterenol-induced arrhythmogenesis.

Analysis of 10-year nationwide population-based data on sex differences in hospitalization for heart failure.

Sex-related factors play an important role in the pathophysiology of heart failure (HF). However, trends in sex-related differences in hospital management for HF are not clear. We identified patients hospitalized for HF through a nationwide database (National Health Insurance in Taiwan), containing 722,272 subjects from 1999 to 2008. Higher incidences of diabetes mellitus (37 vs. 25 %, p < 0.001), thyroid dysfunction (2 vs. 0 %, p < 0.001), and transient cerebral ischemia (2 vs. 1 %, p < 0.05), as well as a lower incidence of chronic lung disease (14 vs. 22 %, p < 0.001) differentiated female HF patients from male HF patients. During this 10-year period, both percentage of HF hospitalization and age-adjusted HF rates significantly increased for total HF sample (1.92 vs. 2.49  ‰, p < 0.05, and 20.44 vs. 27.38/100,000, p < 0.05) and for female (1.76 vs. 2.86  ‰, p < 0.05, and 20.94 vs. 32.12/100,000, p < 0.05), but such changes did not occur among male patients (2.12 vs. 2.09  ‰, p > 0.05, and 19.93 vs. 22.51/100,000, p > 0.05). The age at the time of hospitalization and the length of the hospital stay increased significantly for all HF patients during the 10-year study period. However, the daily cost of hospitalization increased in males, but not in females. Compared to the survivors, patients who died were older and had a longer hospitalization and higher daily cost both in males and females. Through our analysis of the NHI database, we observed trends in factors related to hospitalization of HF patients in Taiwan that may be attributable to sex-related differences in the pathophysiology and treatment strategies for HF.