Magnesium Lithospermate B Protects Against Cisplatin-Induced Acute Kidney Injury via Alleviating Mitochondrial Dysfunction.

Purpose: Apoptosis plays a critical role in cisplatin-induced acute kidney injury (AKI) and is related to mitochondrial dysfunction. Magnesium lithospermate B (Mlb), one of the most important components of Salvia miltiorrhiza Bunge, is mainly used to treat cardiovascular diseases because of its anti-apoptotic effects. The mechanism underlying the protective effect of Mlb against cisplatin-induced AKI remains unclear. In this study, we investigated the protective effect of Mlb on mitochondrial function against apoptosis caused by cisplatin-induced renal injury. Methods: Renal injury induced by cisplatin in mouse renal tubular epithelial cells (mTECs) was measured by quantifying serum creatinine levels, mitochondrial morphology, cell viability, apoptosis, Dynamin-related protein 1(Drp1) expression, etc. The cells were then administered Mlb to determine its protective effects against cisplatin-induced AKI. Results: Mlb treatment significantly reduced serum creatinine levels and pathological injury of renal, inhibited the production of malondialdehyde, and reduced the depletion of superoxide dismutase. In addition, Mlb reduced Bax/Bcl2, cleaved caspase-3/caspase-3, and maintained mitochondrial integrity after AKI. Mlb administration also improved cell viability and reduced the percentage of apoptotic cells in vitro. Furthermore, Mlb reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential, and ameliorated mitochondrial morphological abnormalities by downregulating Drp1 expression. Conclusion: These results indicated that Mlb could protect the kidneys against cisplatin-induced apoptosis by alleviating mitochondrial dysfunction.

Established UPLC-MS/MS procedure for multicomponent quantitative analysis in rat plasma: A contrastive pharmacokinetics study of Qiangshen tablet in normal and kidney yang deficiency syndrome models.

Qiangshen tablet, an important prescription consisting of 14 kinds of Chinese herbal medicines, has been used for decades to treat kidney yang deficiency syndrome (KYDS) in China. Qiangshen tablet has been recorded in ChP (2015 edition) and possesses the effect of strengthening yang, invigorating qi and tonifying kidneys. In this research, a simple, reliable and specific method was established for simultaneous determination of stachydrine, psoralen, isopsoralen, morroniside, paeoniflorin and loganin in normal and KYDS rat plasma after intragastric administration of a Qiangshen tablet suspension by UPLC-MS/MS. Protein precipitation (PP) by acetonitrile and liquid-liquid extraction (LLE) by ethyl acetate - n-butanol (1: 1, v/v) were used for pretreatment of plasma samples. Chromatographic separation of two IS (Internal Standard) and six analytes was achieved using an ACQUITY UPLC® BEH C18 column (2.1 × 100 mm, 1.7 µm). The mobile phase consisted of 0.1% formic acid aqueous solution (solvent A) and acetonitrile (solvent B) with a gradient scheme. Multiple reaction monitoring (MRM) mode with positive and negative ion source switching was applied to perform the mass spectrometric analyses. This method has been validated with good linearity (r ≥ 0.9942) and acceptable precision and accuracy (RSD ≤ 11%, RE from -4.8% to 7.7%). The mean recovery values of the analytes and IS were all ≥68.28%, and the matrix effects ranged from 94.4% to 101.7%. The stability of the IS and analytes was measured throughout the experiment. The results showed significant differences between the pharmacokinetic traits of the analytes in the normal and KYDS groups, suggesting that pharmacokinetic procedures involving these analytes could be modified in cases of KYDS.

Late cure of focal ventricular arrhythmias post-catheter ablation: electrophysiological characteristics and long-term outcome.

PURPOSE: Late cure after a previously failed ablation of ventricular arrhythmias (VAs) is a relatively common phenomenon. The present study sought to delineate the incidence and electrophysiological characteristics of late cure in idiopathic VA patients. METHODS: Totally, 45 idiopathic VA cases (mean age 44 ± 18 years, 27 males) either failed acutely or recurred within 12 h were enrolled in this study. Based on intensive clinical observations in the acute period, 19 (42%) patients demonstrated late cure in the first week after the procedure. RESULTS: The late cure patients had significantly better acute and cumulative ablation effects during the procedure than did those without a late cure. Additionally, they had a prediction that originated from the right ventricular outflow tract, aortic-mitral continuum, and left summit area relative to other sites (13/18 vs 6/27, p < 0.01). In a median follow-up of 24 [14, 46] months, 7/19 (37%) patients had their VAs recurred. The late cure group had significantly more patients cured at long-term follow-up than those without (12/19 vs 0/26, p < 0.01). A cutoff value of the "time to eliminate VAs" > 7.0 s was able to predict a long-term recurrence of the VAs with 62.5% sensitivity and 85.7% specificity. CONCLUSIONS: The late cure of VAs occurs in more than one third of patients who have a seemingly unsuccessful ablation session, which is clustered in the first week after the procedure. However, long-term recurrence of VAs occurred in 37% of the late cure patients, emphasizing the importance of long-term follow-up.

Peri-mitral atrial flutter: personalized ablation strategy based on arrhythmogenic substrate.

Aims: The aim of this study is to characterize the arrhythmogenic substrate for peri-mitral atrial flutter (PMAFL), thereby determining a personalized ablation strategy to treat PMAFL. Methods and results: Thirty-six consecutive PMAFL patients (mean age: 63.8 ± 11.3, 23 males) underwent detailed three-dimensional electroanatomic mapping in left atrium (LA). The LA was divided into septal-anterior wall (SAW), posterior inferior wall (PIW), and mitral isthmus (MI) region, respectively. Ablation strategy was determined based on the endocardial bipolar voltage map. Based on electrophysiological substrates, 10, 17, and 9 cases were classified into iatrogenic, spontaneous, and no-substrate PMAFL, respectively. The mean voltage in SAW was significantly lower in spontaneous PMAFL (iatrogenic: 1.07 ± 0.66 mV; spontaneous: 0.65 ± 0.44 mV; no-substrate: 1.60 ± 0.53 mV, P <0.001), while iatrogenic PMAFL patients had the lowest voltage in MI (0.51 ± 0.23 mV vs. 1.55 ± 0.78 mV, 1.61 ± 0.56 mV, P <0.001). No low-voltage or slow conduction zone was found in the no-substrate PMAFL group. Fifteen spontaneous PMAFLs were successfully terminated by modified septal-anterior (9/10) or conventional anterior ablation line (6/7). Eight iatrogenic PMAFLs (8/10) were terminated by reinforcing the previous ablation areas. Cardioversion without PMAFL ablation was done in no-substrate PMAFL patients. After a median follow-up of 12 (7-39) months, two spontaneous PMAFL patients received redo procedures for recurrence due to "gap" conduction. Conclusions: The ablation strategy for PMAFL patients should be based on the arrhythmogenic substrate, but not the indiscriminate MI ablation. No-substrate PMAFLs during AF ablation could be monitored after cardioversion and might not need further ablation.

Mapping of focal atrial tachycardia with an uninterpretable activation map after extensive atrial ablation: tricks and tips.

BACKGROUND: Atrial tachycardias (ATs) after extensive ablation are increasingly common and challenging arrhythmias. The prolonged intra-atrial conduction time (IACT) during ATs in the milieu may complicate the mapping of focal ATs. In this present study, we aim to characterize the electrophysiological features of ATs in this unique setting and to delineate an effective mapping strategy further. METHODS AND RESULTS: In total, 13 patients (average age, 59±7 years) in a cohort of 80 patients referred for AT ablation were selected for the study. The patients all demonstrated an undistinguishable map not ready to be interpreted the 3-dimensional mapping. A total of 13 ATs were mapped with mean tachycardia cycle length of 296±70 ms. Two activation patterns were identified, which were referred to as pseudo-macroreentry and chaotic activation. The former was a focal AT originating from the vicinity of an area of conduction block with the IACT less than the window of interest duration (4 cases; IACT/window of interest ratio range, 0.93-0.98). The latter refers to a focal AT exhibiting a disorderly color mapping display with IACT exceeding the window of interest duration (9 cases; IACT/window of interest ratio range, 1.02-1.29). The IACT was determined after resetting the annotation. All ATs were successfully eliminated at the originating site. CONCLUSIONS: We delineated a series of focal ATs in the setting of a significantly prolonged IACT encountered in patients after previous extensive ablation. Two activation patterns were identified, which may help facilitate the mapping of focal ATs in this setting.

Tachycardiomyopathy complicated by focal atrial tachycardia: incidence, risk factors, and long-term outcome.

OBJECTIVE: Focal atrial tachycardias (ATs) are known to have the potential to develop tachycardiomyopathy (TCM). The aim of the study was to investigate the incidence, risk factors, and long-term outcome of TCM patients complicated by focal ATs. METHODS AND RESULTS: A total of 237 patients undergoing electrophysiological studies were enrolled, among which 216 patients were diagnosed as focal ATs. In total, 18 patients (8.3%, 13 males) were identified to have TCM. The TCM patients were younger (29.8 ± 20.1 vs. 45.9 ± 17.3; P < 0.000) and were more frequently males (13/18 vs. 80/198; P = 0.014). The ATs were more likely to be persistent (11/18 vs. 32/198; P < 0.001). There was no difference between the 2 groups in terms of the tachycardia cycle length (392 milliseconds vs. 380 milliseconds; P = 0.56) and heart rate (144 bpm vs. 156 bpm; P = 0.15). The persistence and incidence of symptoms and prevalence of structural heart disease were comparable between the groups. In a multivariable analysis, the younger age and persistent nature were independently associated with TCM. In a 56 ± 21-month follow-up, all TCM patients had improved left ventricle ejection fraction after successful catheter ablation or medical therapy (43.9 ± 5.8% vs. 61.1 ± 3.5%; P ＜ 0.05). However, 1 patient suffered sudden cardiac death due to unauthorized withdrawal of the drug and progressive heart failure. CONCLUSIONS: The incidence of TCM in focal ATs patients was 8.3%. Younger age and persistent nature were the independent risk factors of TCM. Most TCM patients had a benign outcome; however, long-term risk of sudden death does exist.