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Heart failure (HF) is a rapidly growing global public health problem. Since HF results in high mortality and re-hospitalization, new effective treatments are desired. Although it remains controversial, omega 3 polyunsaturated fatty acids (n-3 PUFAs), such as the eicosapentaenoic acid and docosahexaenoic acid, have been widely recognized to have benefits for HF. In a large-scale clinical trial regarding secondary prevention of HF by n-3 PUFA (GISSI-HF trial), the supplementation of n-3 PUFA significantly reduced cardiovascular mortality and hospitalization. Other small clinical studies proposed that n-3 PUFA potentially suppresses the ventricular remodeling and myocardial fibrosis, which thereby improves the ventricular systolic and diastolic function both in ischemic and non-ischemic HF. Basic investigations have further supported our understanding regarding the cardioprotective mechanisms of n-3 PUFA against HF. In these reports, n-3 PUFA has protected hearts through (1) anti-inflammatory effects, (2) intervention of cardiac energy metabolism, (3) modification of cardiac ion channels, (4) improvement of vascular endothelial response, and (5) modulation of autonomic nervous system activity. To clarify the pros and cons of n-3 PUFA on HF, we summarized recent evidence regarding the beneficial effects of n-3 PUFA on HF both from the clinical and basic studies.

Levosimendan and milrinone may be used in place of dobutamine to increase cardiac output in septic patients with a low cardiac output due to impaired cardiac function. The effects of the two inotropic agents on cardiac inflammation and left ventricular (LV) performance were examined in mice with cecal ligation and puncture (CLP)-induced sepsis. CLP mice displayed significant cardiac inflammation, as indicated by highly increased pro-inflammatory cytokines and neutrophil infiltration in myocardial tissues. When continuously given, levosimendan prevented but milrinone exaggerated cardiac inflammation, but they significantly reduced the elevations in plasma cardiac troponin-I and heart-type fatty acid-binding protein, clinical markers of cardiac injury. Echocardiographic assessment of cardiac function showed that the effect of levosimendan, given by an intravenous bolus injection, on LV performance was impaired in CLP mice, whereas milrinone produced inotropic responses equally in sham-operated and CLP mice. A lesser effect of levosimendan on LV performance after CLP was also found in spontaneously beating Langendorff-perfused hearts. In ventricular myocytes isolated from control and CLP mice, levosimendan, but not milrinone, caused a large increase in the L-type calcium current. This study represents that levosimendan and milrinone have cardioprotective properties but provide different advantages and drawbacks to cardiac inflammation/dysfunction in sepsis.

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Aims Although the delivery catheter system for pacemaker-lead implantation is a new alternative to the stylet system, no randomized controlled trial has addressed the difference in right ventricular (RV) lead placement accuracy to the septum between the stylet and the delivery catheter systems. This multicentre prospective randomized controlled trial aimed to prove the efficacy of the delivery catheter system for accurate delivery of RV lead to the septum. Methods and results In this trial, 70 patients (mean age 78 ± 11 years; 30 men) with pacemaker indications of atrioventricular block were randomized to the delivery catheter or the stylet groups. Right ventricular lead tip positions were assessed using cardiac computed tomography within 4 weeks of pacemaker implantation. Lead tip positions were classified into RV septum, anterior/posterior edge of the RV septal wall, and RV free wall. The primary endpoint was the success rate of RV lead tip placement to the RV septum. Results Right ventricular leads were implanted as per allocation in all patients. The delivery catheter group had higher success rate of RV lead deployment to the septum (78 vs. 50%; P = 0.024) and narrower paced QRS width (130 ± 19 vs. 142 ± 15 ms P = 0.004) than those in the stylet group. However, there was no significant difference in procedure time [91 (IQR 68–119) vs. 85 (59–118) min; P = 0.488] or the incidence of RV lead dislodgment (0 vs. 3%; P = 0.486). Conclusion The delivery catheter system can achieve a higher success rate of RV lead placement to the RV septum and narrower paced QRS width than the stylet system. Trial registration number jRCTs042200014 (https://jrct.niph.go.jp/en-latest-detail/jRCTs042200014)

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Both forms of preconditioning greatly reduced infaction areas relative to controls. Store depletion generated Ca(2þ) selective currents with strong inward rectification. Preconditioning almost completely suppressed these currents, an effect that was almost blocked by 5HD a selective mitoKATP channel blocker and by intracellular BAPTA. And as assessed by Fura-2 this influx was also blocked by preconditioning. In contrast, the expression at the protein level of both STIM1 and Orai1 was strongly up-regulated by preconditioning and confocal microscopy revealed a higher density of Orai1 channels at the surface membrane.Our results indicate that while the expression of protein components of SOCS in heart cells (STIM1 and Orai1) are up-regulated by preconditioning, influx of Ca(2þ) through SOCS is severely impaired by preconditioning, probably by a slow Ca(2þ)-dependent inactivation process.

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