Bmal1 knockdown in the left stellate ganglion inhibits neural activity and prevents ventricular arrhythmias after myocardial ischemia.

Objectives: The neural activity of the left stellate ganglion (LSG) is closely related to the occurrence of ventricular arrhythmias (VAs). Bmal1 modulates genes associated with neural activity in the central nervous system. However, few studies indicated the role of Bmal1 in the LSG and the subsequent effect on the heart. Therefore, we aimed to investigate the influence of Bmal1 knockdown in the LSG on its neural activity and cardiac electrophysiology and to explore the mechanisms. Materials and methods: We used adeno-associated virus (AAV) to knock down Bmal1 in the LSG. Male beagles were randomized into the Bmal1 knockdown group and the control group. After 4 weeks of injection, the LSG function, neural activity, left ventricular effective refractory period (ERP), and action potential duration (APD) were measured. Electrocardiography for 1 h was recorded for VAs analysis after myocardial ischemia. Nerve growth factor (NGF) and c-fos in the LSG were quantified by immunofluorescence. Transcriptomic analysis was performed to assess the gene expression in the LSG. Results: Bmal1 was sufficiently knocked down by AAV. Compared with the control group, heart rate variability (HRV) in the knockdown group was altered. Bmal1 knockdown inhibited neural activity and function of LSG. It also prolonged ERP as well as APD90. Ischemia-induced VAs were significantly reduced. Nerve growth factor (NGF) and c-fos in the LSG were reduced. Bmal1 knockdown led to the expression changes of genes associated with neural activity in the LSG. Conclusion: Bmal1 knockdown in the LSG suppresses neural activity and prevents ventricular arrhythmias after myocardial ischemia.

Melatonin improves cardiac remodeling and brain-heart sympathetic hyperactivation aggravated by light disruption after myocardial infarction.

Light in the external environment might affect cardiovascular function. The light disruption seems to be related to changes in cardiovascular physiological functions, and disturbing light may be a risk factor for cardiovascular diseases. Prior studies have found that light disruption after myocardial infarction (MI) exacerbates cardiac remodeling, and the brain-heart sympathetic nervous system may be one of the key mechanisms. However, how to improve light-disrupted cardiac remodeling remains unclear. Melatonin is an indoleamine secreted by the pineal gland and controlled by endogenous circadian oscillators within the suprachiasmatic nucleus, which is closely associated with light/dark cycle. This study aimed to explore whether melatonin could improve light-disrupted cardiac remodeling and modulate the brain-heart sympathetic nervous system. Our study revealed that light disruption reduced serum melatonin levels, aggravated cardiac sympathetic remodeling, caused overactivation of the brain-heart sympathetic nervous system, exacerbated cardiac dysfunction, and increased cardiac fibrosis after MI, while melatonin treatment improved light disruption-exacerbated cardiac remodeling and brain-heart sympathetic hyperactivation after MI. Furthermore, RNA-Seq results revealed the significant changes at the cardiac transcription level. In conclusion, melatonin may be a potential therapy for light-disrupted cardiac remodeling.

Ultrasound-guided injection of botulinum toxin type A blocks cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic myocardial infarction.

BACKGROUND: Strategies to improve various cardiovascular diseases by blocking cardiac sympathetic ganglion have been increasingly available currently. Botulinum toxin type A (BTA), a typical neurotoxin, has been shown to block neural transmission in a safe and long-lasting manner. OBJECTIVE: The aim of the present preclinical study was to assess the efficacy of BTA microinjection to alleviate cardiac remodeling after chronic myocardial infarction (MI) by blocking cardiac sympathetic ganglion in a canine model. METHODS: Beagles were randomly divided into a control group (saline microinjection with sham surgery), an MI group (saline microinjection with MI), and an MI + BTA group (BTA microinjection with MI). Ultrasound-guided percutaneous BTA or saline injection into the left stellate ganglion (LSG) was performed followed by MI induction via left anterior descending artery occlusion (LADO) or sham surgery. After 30 days, electrocardiography, Doppler echocardiography, LSG function, neural activity, and ventricular electrophysiological detection were performed in all experimental dogs. At the end, LSG and ventricular tissues were collected for further detection. RESULTS: BTA treatment significantly inhibited LSG function and neural activity and improved heart rate variability. Additionally, BTA application alleviated ventricular remodeling, ameliorated cardiac function, and prevented ventricular arrhythmias after 30-day chronic LADO-induced MI. CONCLUSION: Ultrasound-guided percutaneous microinjection of BTA can block cardiac sympathetic ganglion to improve cardiac remodeling in a large animal model of chronic LADO-induced MI. Ultrasound-guided BTA microinjection has potential for clinical application as a novel cardiac sympathetic ganglion blockade strategy for MI.