Knockdown regarding Tmem234 in zebrafish ends in proteinuria
Background Short-term variability (STV) of repolarization of the monophasic action potential duration (MAPD) or activation recovery interval (ARI) on the intracardiac electrogram (EGM) increases abruptly prior to the occurrence of ventricular arrhythmias in the chronic AV-block (CAVB) dog model. Therefore, this parameter might be suitable for continuous monitoring of imminent arrhythmias using the EGM stored on an implanted device. However, 24/7 monitoring would require automatic STVARI measurement by the device. Objective To evaluate a newly developed automatic measurement of STVARI for prediction of dofetilide-induced torsade de pointes (TdP) arrhythmias in the CAVB-dog. Methods Two retrospective analyses were done on data from recently performed dog experiments. (1) In seven anesthetized CAVB-dogs, the new automatic STVARI method was compared with the gold standard STVMAPD at baseline and after dofetilide administration (0.025 mg/kg in 5 min). (2) The predictive value of the automatic method was compared tlar arrhythmias in the CAVB-dog. Future integration of this method into implantable devices could provide the opportunity for 24/7 monitoring of arrhythmic risk.Background Many heart failure (HF) patients admitted to cardiac rehabilitation (CR) centers have a cardiac resynchronization therapy (CRT) device. However, information about the efficacy and safety of exercise rehabilitation in HF patients with a CRT device is scant. We assessed the effects of exercise rehabilitation in HF patients with a CRT device. Methods and Results The PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, PsycInfo, China Biology Medicine, Wanfang, and China National Knowledge Infrastructure databases were searched comprehensively to identify randomized controlled trials (RCTs) published between January 1, 1990 and July 1, 2019 on exercise rehabilitation in HF patients with CRT devices. We identified seven studies published from 2006 to 2019, including 661 patients with an intervention duration of 8 to 24 weeks. Three studies reported all-cause mortality and serious adverse events, and no significant difference was found between exercise rehabilitation patients and contrHF patients with a CRT device. Furthermore, exercise training was associated with better HRQOL on follow-up.Increasing evidence shows that Curcumin (Cur) has a protective effect against cardiovascular diseases. However, the role of Cur in the electrophysiology of cardiomyocytes is currently not entirely understood. Therefore, the present study was conducted to investigate the effects of Cur on the action potential and transmembrane ion currents in rabbit ventricular myocytes to explore its antiarrhythmic property. The whole-cell patch clamp was used to record the action potential and ion currents, while the multichannel acquisition and analysis system was used to synchronously record the electrocardiogram and monophasic action potential. The results showed that 30 μmol/L Cur shortened the 50 and 90% repolarization of action potential by 17 and 7%, respectively. In addition, Cur concentration dependently inhibited the Late-sodium current (INa.L), Transient-sodium current (INa.T), L-type calcium current (ICa.L), and Rapidly delayed rectifying potassium current (IKr), with IC50 values of 7.53, 398.88, 16.66, and 9.96 μmol/L, respectively. α-cyano-4-hydroxycinnamic molecular weight Importantly, the inhibitory effect of Cur on INa.L was 52.97-fold higher than that of INa.T. Moreover, Cur decreased ATX II-prolonged APD, suppressed the ATX II-induced early afterdepolarization (EAD) and Ca2+-induced delayed afterdepolarization (DAD) in ventricular myocytes, and reduced the occurrence and average duration of ventricular tachycardias and ventricular fibrillations induced by ischemia-reperfusion injury. In conclusion, Cur inhibited INa.L, INa.T, ICa.L, and IKr; shortened APD; significantly suppressed EAD and DAD-like arrhythmogenic activities at the cellular level; and exhibited antiarrhythmic effect at the organ level. It is first revealed that Cur is a multi-ion channel blocker that preferentially blocks INa.L and may have potential antiarrhythmic property.Tendon geometry and tissue properties are important determinants of tendon function and injury risk and are altered in response to ageing, disease, and physical activity levels. The purpose of this study was to compare free Achilles tendon geometry and mechanical properties between trained elite/sub-elite middle-distance runners and a healthy control group. Magnetic resonance imaging (MRI) was used to measure free Achilles tendon volume, length, average cross-sectional area (CSA), regional CSA, moment arm, and T2* relaxation time at rest, while freehand three-dimensional ultrasound (3DUS) was used to quantify free Achilles tendon mechanical stiffness, Young's modulus, and length normalised mechanical stiffness. The free Achilles tendon in trained runners was significantly shorter and the average and regional CSA (distal end) were significantly larger compared to the control group. Mechanical stiffness of the free Achilles tendon was also significantly higher in trained runners compared to controls, which was explained by the group differences in tendon CSA and length. T2* relaxation time was significantly longer in trained middle-distance runners when compared to healthy controls. There was no relationship between T2* relaxation time and Young's modulus. The longer T2* relaxation time in trained runners may be indicative of accumulated damage, disorganised collagen, and increased water content in the free Achilles tendon. A short free Achilles tendon with large CSA and higher mechanical stiffness may enable trained runners to rapidly transfer high muscle forces and possibly reduce the risk of tendon damage from mechanical fatigue.Weightlessness and physical inactivity have deleterious cardiovascular effects. The space environment and its ground-based models offer conditions to study the cardiovascular effects of physical inactivity in the absence of other vascular risk factors, particularly at the macro- and microcirculatory levels. However, the mechanisms involved in vascular dysfunction and remodeling are not sufficiently studied in the context of weightlessness and its analogs including models of physical inactivity. Here, we summarize vascular and microvascular changes induced by space flight and observed in models of microgravity and physical inactivity and review the effects of prophylactic strategies (i.e., countermeasures) on vascular and microvascular function. We discuss physical (e.g., exercise, vibration, lower body negative pressure, and artificial gravity) and nutritional/pharmacological (e.g., caloric restriction, resveratrol, and other vegetal extracts) countermeasures. Currently, exercise countermeasure appears to be the most effective to protect vascular function.