Abstract

Wenxin-Keli (WXKL) is a Chinese herbal compound reported to be of benefit in the treatment of cardiac arrhythmia, cardiac inflammation, and heart failure. Amiodarone is a noncompetitive inhibitor of the α- and β-adrenergic receptors and prevents calcium influx in the slow-response cells of the sinoatrial and atrioventricular nodes. Overexpression of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias. We hypothesised that administration of WXKL and amiodarone can reduce the incidence of arrhythmias by regulating CaMKII signal transduction. A total of 100 healthy Sprague Dawley rats were used in the study. The rats were randomly divided into four groups (a sham group, a myocardial infarction (MI) group, a WXKL-treated group, and an amiodarone-treated group). A myocardial infarction model was established in these rats by ligating the left anterior descending coronary artery for 4 weeks. Western blotting was used to assess CaMKII, p-CaMKII (Thr-286), PLB, p-PLB (Thr-17), RYR2, and FK binding protein 12.6 (FKBP12.6) levels. The Ca2+ content in the sarcoplasmic reticulum (SR) and the calcium transient amplitude were studied by confocal imaging using the fluorescent indicator Fura-4. In conclusion, WXKL may inhibit heart failure and cardiac arrhythmias by regulating the CaMKII signal transduction pathway similar to amiodarone.

Highlights

  • Cardiovascular diseases are the most common threat to human health worldwide and are the leading cause of morbidity in human populations

  • The 75 MI rats were randomly assigned to three treatment groups: the MI group (N = 25), in which the rats were treated with the vehicle alone for oral administration; the WXKL group (N = 25), in which the rats were treated with the WXKL compound (4 g/kg/day) for oral administration; and the amiodarone group (N = 25), in which the rats were treated with amiodarone (30 mg/kg/day) for oral administration

  • We evaluated cardiac systolic function by a combination of ECG measurements that included the EF, the FS, EDV, ESV, the left ventricular end-diastolic dimension (LVDd), the LVDs, and the stroke volume (SV)

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Summary

Introduction

Cardiovascular diseases are the most common threat to human health worldwide and are the leading cause of morbidity in human populations. Epidemiological data show that at present the number of patients with heart failure has increased to 22.5 million globally and is still increasing at a rate of 2 million patients per year. The 5-year survival rate of patients with heart failure is similar to that of patients with malignant tumours, and mortality continues to increase despite advances in our understanding of the underlying mechanisms of the disease and the development of new treatments. More than a quarter of a million patients die of heart failure annually in the United States [1]. The risk of sudden cardiac death in heart failure patients is six to nine times that of the general population, and approximately half of these patients die of ventricular arrhythmias. Drugs that inhibit the adrenergic and renin-angiotensin aldosterone systems have improved the survival of individual patients receiving treatment, deaths

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