Calcium-mediated DAD in membrane potentials and triggered activity in atrial myocytes of ETV1f / fMyHCCre /+ mice.

The E-twenty-six variant 1 (ETV1)-dependent transcriptome plays an important role in atrial electrical and structural remodelling and the occurrence of atrial fibrillation (AF), but the underlying mechanism of ETV1 in AF is unclear. In this study, cardiomyocyte-specific ETV1 knockout (ETV1f/fMyHCCre/+, ETV1-CKO) mice were constructed to observe the susceptibility to AF and the underlying mechanism in AF associated with ETV1-CKO mice. AF susceptibility was examined by intraesophageal burst pacing, induction of AF was increased obviously in ETV1-CKO mice than WT mice. Electrophysiology experiments indicated shortened APD50 and APD90, increased incidence of DADs, decreased density of ICa,L in ETV1-CKO mice. There was no difference in VINACT,1/2 and VACT,1/2, but a significantly longer duration of the recovery time after inactivation in the ETV1-CKO mice. The recording of intracellular Ca2+ showed that there was significantly increased in the frequency of calcium spark, Ca2+ transient amplitude, and proportion of SCaEs in ETV1-CKO mice. Reduction of Cav1.2 rather than NCX1 and SERCA2a, increase RyR2, p-RyR2 and CaMKII was reflected in ETV1-CKO group. This study demonstrates that the increase in calcium spark and SCaEs corresponding to Ca2+ transient amplitude may trigger DAD in membrane potential in ETV1-CKO mice, thereby increasing the risk of AF.

Acute Effects of Ibrutinib on Ventricular Arrhythmia in Spontaneously Hypertensive Rats.

BACKGROUND: The Bruton's Tyrosine Kinase Inhibitor ibrutinib is associated with ventricular arrhythmia (VA) and sudden death. However, the pro-arrhythmic electrophysiological dysregulation that results from ibrutinib with age and cardiovascular disease is unknown. OBJECTIVES: This study sought to investigate the acute effects of ibrutinib on left ventricular (LV) VA vulnerability, cytosolic calcium dynamics, and membrane electrophysiology in old and young spontaneous hypertensive rats (SHRs). METHODS: Langendorff-perfused hearts of young (10 to 14 weeks) and old (10 to 14 months) SHRs were treated with ibrutinib (0.1 µmol/l) or vehicle for 30 min. Simultaneously, LV epicardial action potential and cytosolic calcium transients were optically mapped following an incremental pacing protocol. Calcium and action potential dynamics parameters were analyzed. VA vulnerability was assessed by electrically inducing ventricular fibrillations (VFs) in each heart. Western blot analysis was performed on LV tissues. RESULTS: Ibrutinib treatment resulted in higher vulnerability to VF in old SHR hearts (27.5 ± 7.5% vs. 5.7 ± 3.7%; p = 0.026) but not in young SHR hearts (8.0 ± 4.9% vs. 0%; p = 0.193). In old SHR hearts, following ibrutinib treatment, action potential duration (APD) alternans (p = 0.008) and APD alternans spatial discordance (p = 0.027) were more prominent. Moreover, calcium transient duration 50 was longer (p = 0.032), calcium amplitude alternans ratio was significantly lower (p = 0.001), and time-to-peak of calcium amplitude was shorter (p = 0.037). In young SHR hearts, there were no differences in calcium and APD dynamics. CONCLUSIONS: Ibrutinib-induced VA is associated with old age in SHR. Acute dysregulation of calcium and repolarization dynamics play important roles in ibrutinib-induced VF.

A novel ECG signal compression method using spindle convolutional auto-encoder.

BACKGROUND AND OBJECTIVES: With rapid development of telehealth system and cloud platform, traditional 12-ECG signals with high resolution generate heavy burdens in data storage and transmission. This problem is increasingly addressed with various ECG compression methods. The important objective of compression method is to achieve a high-ratio and quality guaranteed compression. Consequently, to achieve this objective, this work presents a deep-learning-based spindle convolutional auto-encoder. The spindle structure achieves the high-ratio compression by reducing the dimension and guarantees the quality by increasing the dimension and end-to-end framework. METHODS: The spindle convolutional auto-encoder provides a high-ratio and quality-guaranteed ECG compression. It is composed of two parts as convolutional encoder and convolutional decoder with functional layers. By convolutional operation, the local information can be extracted. The spindle structure is increasing dimension in first few layers to obtain sufficient information to guarantee compression quality. And it is reducing dimension in last few layers to merge the information into a code for high-ratio compression. Meanwhile, the end-to-end framework is to obtain the optimum encoding for compression to improve the reconstruction performance. RESULTS: Compression performance is validated with records from MIT-BIH database. The proposed method achieves high compression ratio of 106.45 and low percentage root mean square difference of 8.00%. Compared with basic convolutional auto-encoder, the spindle structure improves the compression quality with lower losses. CONCLUSIONS: The spindle convolutional auto-encoder performs a high-ratio and quality-guaranteed compression. It can be considered as a promising compression technique used in tele-transmission and data storage.

Calcium-Mediated Oscillation in Membrane Potentials and Atrial-Triggered Activity in Atrial Cells of Casq2R33Q/R33Q Mutation Mice.

Aim: We investigated the underlying mechanisms in atrial fibrillation (AF) associated with R33Q mutation and Ca2+-triggered activity. Methods and Results: We examined AF susceptibility with intraesophageal burst pacing in the sarcoplasmic reticulum (SR) Ca2+ leak model calsequestrin 2 R33Q (Casq2R33Q/R33Q) mice. Atrial trigger appeared in R33Q mice but not WT mice (17.24%, 5/29 vs. 0.00%, 0/32, P < 0.05). AF was induced by 25 Hz pacing in R33Q mice (48.27%, 14/29 vs. 6.25%, 2/32, P < 0.01). The mice were given 1.5 mg/kg isoproterenol (Iso), and the incidences of AF increased (65.51%, 19/29 vs. 9.21%, 3/32, P < 0.01). Electrophysiology experiments and the recording of intracellular Ca2+ indicated significant increases in the Ca2+ sparks (5.24 ± 0.75 100 µM-1.s-1 vs. 0.29 ± 0.04 100 µM-1.s-1, n = 20, P < 0.05), intracellular free Ca2+ (0.238 ± 0.009 µM vs. 0.172 ± 0.006 µM, n = 20, P < 0.05), Ca2+ wave (11.74% vs. 2.24%, n = 20, P < 0.05), transient inward current (ITi) (-0.56 ± 0.02 pA/pF vs. -0.42 ± 0.01 pA/pF, n = 10, P < 0.05), and oscillation in membrane potentials (10.71%, 3/28 vs. 4.16%, 1/24, P < 0.05) in the R33Q group, but there was no significant difference in the L-type calcium current. These effects were enhanced by Iso, and the inhibition of calmodulin-dependent protein kinase II (CaMKII) by 1 µM KN93 reversed the effects of Iso on Ca2+ sparks (5.01 ± 0.66 100 µm-1.s-1 vs. 11.33 ± 1.63 100 µm-1.s-1, P < 0.05), intracellular Ca2+ (0.245 ± 0.005 µM vs. 0.324 ± 0.008 µM, P < 0.05), Ca2+ wave (12.35% vs. 17.83%, P < 0.05), ITi (-0.61 ± 0.02 pA/pF vs. -0.78 ± 0.03 pA/pF, n = 10, P < 0.05), and oscillation in membrane potential (17.85% 5/28 vs. 32.17% 9/28, P < 0.05). The reduction of ryanodine receptor 2 (RyR2) stable subunits (Casq2, triadin, and junctin) rather than RYR2 and the increase in CaMKII, phosphor-CaMKII, phosphor-RyR2 (Ser 2814), SERCA, and NCX1.1 was reflected in the R33Q group. Conclusion: This study demonstrates that the increase in spontaneous calcium elevations corresponding to ITi that may trigger the oscillation in membrane potentials in the R33Q group, thereby increasing the risk of AF. The occurrence of spontaneous calcium elevations in R33Q atrial myocytes is due to the dysfunction of RyR2 stable subunits, CaMKII hyperactivity, and CaMKII-mediated RyR phosphorylation. An effective therapeutic strategy to intervene in Ca2+-induced AF associated with the R33Q mutation may be through CaMKII inhibition.

[Vaginal birth after previous cesarean section in low-resource countries: healthcare chain and materno-fetal follow-up]. / Accouchement sur utérus cicatriciel dans les pays à faibles ressources: circuit de prise en charge et devenir materno-fœtal.

The rate of uterine scars, an established risk factor for obstetric morbidity, is increasing worldwide. In developing countries, spontaneous uterine ruptures may constitute 87.4% of cases. Tratment is a problem in modern obstetrics, in particular in these countries. This study aims to describe healthcare chain and materno-fetal follow-up of post-partum women with uterine scar in three university hospitals in the city of Yaoundé in order to highlight morbidity management problems in low-resource countries at the dawn of sustainable development goals. We conducted a cross-sectional descriptive study based on the collection of prospective data over a period of six months in 2014. The study included all consenting post-partum women with uterine scar, having given birth to a gestational at a gestational age greater than or equal to a total of 28 weeks of amenorrhea. The sampling was consecutive and exhaustive. Chi square test statistic was applied in all research areas, with a reliability threshold of p≤ 0.05. Data on 252 women with uterine scars, reflecting a rate of 8% (252/3145), were collected during the study period. Prenatal consultations were performed by inadequate staff in an inadequate sanitary structure in 30% of cases. Women were referred due to delivery complications after first admission to an inadequate sanitary structure in 25% of cases (6 uterine ruptures and 7 dead fetus before admission). There was indication for cesarean section/laparotomy on admission in 39% of cases; the rate of vaginal delivery was of 23%; there was indication for trial of scar in 30% of cases, with a success rate of 76.3%. Vaginal delivery was related to parity, a history of vaginal delivery, fetal macrosomia and was inversely related to the number of scars. Maternal mortality was zero and cesarean section was related to materno-fetal morbidity. The poor quality of prenatal consultations and the management of delivery are the main determinants of problems during vaginal birth after cesarean section in our environment. The establishment of a system facilitating access to skilled health care practitioners/adequate health care facilities for pregnant women with uterine scar would improve the prognosis of post-partum women with uterine scar.