Identification of alternative splicing and RNA-binding proteins involved in myocardial ischemia-reperfusion injury.

Alternative splicing (AS) and RNA-binding proteins (RBPs) have been implicated in various cardiovascular diseases. Yet, a comprehensive understanding of their role in myocardial ischemia-reperfusion injury (MIRI) remains elusive. We aimed to identify potential therapeutic targets for MIRI by studying genome-wide changes in AS events and RBPs. We analyzed RNA-seq data from ischemia-reperfusion mouse models and the control group from the GSE130217 data set using Splicing Site Usage Variation Analysis software. We identified 28 regulated alternative splicing events (RASEs) and 47 differentially expressed RBP (DE-RBP) genes in MIRI. Most variable splicing events were involved in cassette exon, alternative 5' splice, alternative 3' splice, and retained intron types. Gene Ontology and Kyoto Encyclopedia of Genes (KOBAS 2.0 server) and Genomes pathway enrichment analyses showed that the differentially expressed variable splicing and RBP genes were mainly enriched in pathways related to myocardial function. The RBP-RASE network demonstrated a common variance relationship between DE-RBPs and RASEs, indicating that RBPs regulate variable shear events in MIRI. This study systematically identified important alterations in RASEs and RBPs in MIRI, expanding our understanding of the underlying pathogenesis of MIRI.

Impaired coronary flow reserve in patients with supra-normal left ventricular ejection fraction at rest.

PURPOSE: Recently, a "U" hazard ratio curve between resting left ventricular ejection fraction (LVEF) and prognosis has been observed in patients referred for routine clinical echocardiograms. The present study sought to explore whether a similar "U" curve existed between resting LVEF and coronary flow reserve (CFR) in patients without severe cardiovascular disease (CVD) and whether impaired CFR played a role in the adverse outcome of patients with supra-normal LVEF (snLVEF, LVEF ≥ 65%). METHODS: Two hundred ten consecutive patients (mean age 52.3 ± 9.3 years, 104 women) without severe CVD underwent clinically indicated rest/dipyridamole stress electrocardiography (ECG)-gated 13 N-ammonia positron emission tomography/computed tomography (PET/CT). Major adverse cardiac events (MACE) were followed up for 27.3 ± 9.5 months, including heart failure, late revascularization, re-hospitalization, and re-coronary angiography for any cardiac reason. Clinical characteristics, corrected CFR (cCFR), and MACE were compared among the three groups categorized by resting LVEF detected by PET/CT. Dose-response analyses using restricted cubic spline (RCS) functions, multivariate logistic regression, and Kaplan-Meier survival analysis were conducted to evaluate the relationship between resting LVEF and CFR/outcome. RESULTS: An inverted "U" curve existed between resting LVEF and cCFR (p = 0.06). Both patients with snLVEF (n = 38) and with reduced LVEF (rLVEF, LVEF < 55%) (n = 66) displayed a higher incidence of reduced cCFR than those with normal LVEF (nLVEF, 55% ≤ LVEF < 65%) (n = 106) (57.9% vs 54.5% vs 34.3%, p < 0.01, respectively). Both snLVEF (p < 0.01) and rLVEF (p < 0.05) remained independent predictors for reduced cCFR after multivariable adjustment. Patients with snLVEF encountered more MACE than those with nLVEF (10.5% vs 0.9%, log-rank p = 0.01). CONCLUSIONS: Patients with snLVEF are prone to impaired cCFR, which may be related to the adverse prognosis. Further investigations are warranted to explore its underlying pathological mechanism and clinical significance.

[Effects of amiodarone versus sotalol in treatment of atrial fibrillation: a random controlled clinical study].

OBJECTIVE: To evaluate the effects and adverse reactions of amiodarone and sotalol in treatment of atrial fibrillation. METHODS: One hundred and two patients with atrial fibrillation, 56 males and 46 females, aged 56 +/- 11, were randomized into 2 equal groups: amiodarone group, taking amiodarone 600 mg/d for 7 days, 400 mg/d for 7 days, 200 mg/d for 7 days, and then 200 mg/d as maintenance dosage if conversion to sinus rhythm occurred; and sotalol group, taking sotalol 40-80 mg/d for one week, 160 mg/d for 2 weeks and then 40-80 mg/d as maintenance dosage if conversion to sinus rhythm occurred. If the cardiac rhythm failed to be converted to sinus rhythm after three week the medication was stopped. All the patients were followed up for 12-24 months and therapeutic effects were evaluated by echocardiography, electrocardiogram and Holter monitor. RESULTS: (1) Conversion to sinus rhythm occurred in 40 patients in the amiodarone group with an effective rate of 78.4%, and in 36 patients in the sotalol group with an effective rate of 70.6%. (2) Conversion to sinus rhythm occurred in the first week in 34 patients of the amiodarone group and in 10 patients of the sotalol group. (3) 67.5% of the patients with conversion to sinus rhythm in the amiodarone group and 41.7% of the patients with conversion to sinus rhythm in the sotalol group maintained sinus rhythm in the following 12 months; and 44.4% patients with conversion to sinus rhythm in the amiodarone group and 26.7% of the patients with conversion to sinus rhythm in the following 24 months. (4) 10 patients in the sotalol group taking a maintenance dosage of 80 mg/d showed atrial ventricular block and severe bradycardia during the follow-up of 6-2 months, then the medication was stopped, but there was no severe arrhythmia in amiodarone group. (5) It was difficult to maintain sinus rhythm when atrial fibrillation lasting longer than 12 months was a predictive factor of failure to maintain sinus rhythm. CONCLUSION: There is no significant difference between amiodarone and sotalol in converting atrial fibrillation to sinus rhythm. However, amiodarone is more effective in maintenance of sinus rhythm than sotalol. The adverse reaction of amiodarone on heart is less severe than that of sotalol.