Bering Engberg (greecenepal88)

07-1.91) in group without β-blocker in first-stage population; adjusted P = 0.42, HR = 0.85 (0.56-1.28) in group with β-blocker use and adjusted P = 0.015, HR = 1.39 (1.06-1.82) in group without β-blocker in replicated stage. Functional analysis indicated that rs17117699-G allele increased the activity of OMA1 assessed by the ratio of S-OPA1 to L-OPA1 and suppressed cells proliferation under ISO treatment when compared with rs17117699-T allele. Furthermore, OMA1 functioned downstream of β-adrenergic receptor signaling and ISO-induced OPA1 cleavage is dependent on OMA1. CONCLUSIONS Our findings demonstrate that rs17117699T>G in OMA1 increases the risk of HF mortality via enhancing its OPA1 cleavage activity. It is a promising potential treatment target for HF. CLINICAL TRIAL REGISTRATION NCT03461107. https//;cond=Heart+Failure&cntry=CN&rank=1.PURPOSE The melatonin receptor (MT) agonist ramelteon has a higher affinity to MT1 than for MT2 receptors and induces cardioprotection by involvement of mitochondrial potassium channels. Activation of mitochondrial potassium channels leads to release of free radicals. We investigated whether (1) ramelteon-induced cardioprotection is MT2 receptor specific and (2) if free radicals are involved in ramelteon-induced cardioprotection. METHODS Hearts of male Wistar rats were randomized, placed on a Langendorff system, and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to 33 min of global ischemia and 60 min of reperfusion. Before ischemia hearts were perfused with ramelteon (Ram) with or without the MT2 receptor inhibitor 4-phenyl-2-propionamidotetralin (4P-PDOT+Ram, 4P-PDOT). In subsequent experiments, ramelteon was administered together with the radical oxygen species (ROS) scavenger N-2-mercaptopropionylglycine (MPG+Ram). To determine whether the blockade of ramelteon-induced cardioprotection can be restored, we combined ramelteon and MPG with mitochondrial permeability transition pore (mPTP) inhibitor cyclosporine A (CsA) at different time points. Infarct size was determined by triphenyltetrazolium chloride (TTC) staining. RESULTS Ramelteon-induced infarct size reduction was completely blocked by 4P-PDOT and MPG. Ramelteon and MPG combined with CsA before ischemia were not cardioprotective but CsA at the onset of reperfusion could restore infarct size reduction. CONCLUSIONS This study shows for the first time that despite the higher affinity to MT1 receptors, (1) ramelteon-induced cardioprotection involves MT2 receptors, (2) cardioprotection requires ROS release, and (3) inhibition of the mPTP can restore infarct size reduction.PURPOSE Atrial fibrillation (AF) is the most common cardiac arrhythmia with a considerable impact on patients' quality of life (QoL). METHODS This prospective, multicenter, observational study aimed to evaluate the effect of oral treatment with controlled-release (CR) flecainide on AF patients' QoL and treatment compliance during a 12-week period. A total of 70 sites enrolled consecutive patients with paroxysmal (PAF) or persistent AF (PerAF), treated with flecainide CR in the context of a rhythm control strategy. TrichostatinA The effect on QoL was assessed by the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale (CCS-SAF). RESULTS In total, 679 patients (53.2% females, 66 ± 11.7 years, 86.9% PAF) were included. Prior antiarrhythmic medication had been administered in 43.8% of patients. A daily dose of 200 mg was administered to 66.4% of patients by the end of study. Flecainide CR resulted in a significant reduction in the CCS-SAF score (mean (SD)) at the end of the study as compared with baseline (1.32 (0.57) vs 1.64 (0.73), p less then 0.0001). Flecainide CR significantly reduced the CCS-SAF score both in PAF (1.27 (0.52) vs 1.61 (0.72), p less then 0.0001) as well as in PerAF (1.63(0.77) vs