Impact of Ghrelin on Ventricular Arrhythmia and Related Mechanism After Myocardial Infarction

Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Zhengtao Hu ◽  
Ting Zhang ◽  
Yong Mei ◽  
Nan Sun ◽  
Kun Lv ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Arrhythmia ◽  
Sympathetic Nerve ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Ischemic Heart ◽  
Autonomic Nerve ◽  
Protective Effects ◽  
Autonomic Nerve Function ◽  
Ventricular Fibrillation Threshold

<b><i>Introduction:</i></b> Ghrelin is an endogenous peptide with potential protective effects on ischemic heart. <b><i>Methods:</i></b> Synthetic ghrelin was administered (100 μg·kg<sup>-1</sup> subcutaneous injection, twice daily) for 4 weeks in a rat model of myocardial infarction (MI) with coronary artery occlusion. At the 5th week, electrocardiogram, monophasic action potentials and autonomic nerve function were evaluated. Cardiac tyrosine hydroxylase (TH) was determined by immunofluorescence staining. <b><i>Results:</i></b> MI significantly increased sympathetic nerve activity (SNA) and ventricular arrhythmias, and prolonged APD dispersion and APD alternans (<i>p</i> &#x3c; 0.01). Ghrelin treatment significantly increased ventricular fibrillation threshold (VFT), shortened APD dispersion and APD alternans, inhibited SNA and promoted vagus nerve activities (<i>p</i> &#x3c; 0.01). Ghrelin also markedly reversed abnormal expression of TH in the peri-infarcted area of the heart (<i>p</i> &#x3c; 0.01). <b><i>Discussion/Conclusion:</i></b> Ghrelin provides a sustained electrophysiological protection by the increase of VFT and improvement of APD dispersion and APD alternans. The mechanism may be related to the regulation of autonomic nerve and sympathetic nerve remodeling. Thus, ghrelin represents a novel drug to prevent ventricular arrhythmia in ischemic heart disease.

scholarly journals Blockade of NaV1.8 Increases the Susceptibility to Ventricular Arrhythmias During Acute Myocardial Infarction

2021 ◽  
Vol 8 ◽  
Author(s):  
Baozhen Qi ◽  
Shimo Dai ◽  
Yu Song ◽  
Dongli Shen ◽  
Fuhai Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Ventricular Fibrillation ◽  
Refractory Period ◽  
Ventricular Arrhythmias ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Effective Refractory Period ◽  
Control Group ◽  
Ventricular Fibrillation Threshold

SCN10A/NaV1.8 may be associated with a lower risk of ventricular fibrillation in the setting of acute myocardial infarction (AMI), but if and by which mechanism NaV1.8 impacts on ventricular electrophysiology is still a matter of debate. The purpose of this study was to elucidate the contribution of NaV1.8 in ganglionated plexi (GP) to ventricular arrhythmias in the AMI model. Twenty beagles were randomized to either the A-803467 group (n = 10) or the control group (n = 10). NaV1.8 blocker (A-803467, 1 μmol/0.5 mL per GP) or DMSO (0.5 mL per GP) was injected into four major GPs. Ventricular effective refractory period, APD90, ventricular fibrillation threshold, and the incidence of ventricular arrhythmias were measured 1 h after left anterior descending coronary artery occlusion. A-803467 significantly shortened ventricular effective refractory period, APD90, and ventricular fibrillation threshold compared to control. In the A-803467 group, the incidence of ventricular arrhythmias was significantly higher compared to control. A-803467 suppressed the slowing of heart rate response to high-frequency electrical stimulation of the anterior right GP, suggesting that A-803467 could inhibit GP activity. SCN10A/NaV1.8 was readily detected in GPs, but was not validated in ventricles by quantitative RT-PCR, western blot and immunohistochemistry. While SCN10A/NaV1.8 is detectible in canine GPs but not in ventricles, blockade of NaV1.8 in GP increases the incidence of ventricular arrhythmias in AMI hearts. Our study shows for the first time an influence of SCN10A/NaV1.8 on the regulation of ventricular arrhythmogenesis via modulating GP activity in the AMI model.

Some Problems Concerning Coronary Artery Occlusion and Acute Myocardial Infarction

Circulation ◽  
1969 ◽  
Vol 40 (5s4) ◽  
Author(s):  
DONALD B. HACKEL ◽  
E. HARVEY ESTES ◽  
ABE WALSTON ◽  
STEPHEN KOFF ◽  
EUGENE DAY
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Artery ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion

Abstract 12: EMMPRIN-Targeted Magnetic Nanoparticles for in vivo Visualization and Regression of Acute Myocardial Infarction in a Model of Acute Coronary Artery Occlusion

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Irene Cuadrado ◽  
Maria Jose Garcia Miguel ◽  
Irene Herruzo ◽  
Mari Carmen Turpin ◽  
Ana Martin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Extracellular Matrix ◽  
Coronary Artery ◽  
Left Ventricle ◽  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Gadolinium Enhancement

Extracellular matrix metalloproteinase inducer EMMPRIN, is highly expressed in patients with acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including MMP-9 and MMP-13. To prevent Extracellular matrix degradation and cardiac cell death we targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles with an EMMPRIN binding peptide AP9 conjugated (NAP9), or an AP9 scramble peptide as a negative control (NAPSC). NAP9 binds to endogenous EMMPRIN as detected by confocal microscopy of cardiac myocytes and macrophages incubated with NAP and NAPSC in vitro, and in vivo in mouse hearts subjected to left anterior descending coronary artery occlusion (IV injection 50mγ/Kg NAP9 or NAP9SC). Administration of NAP9 at the same time or 1 hour after AMI reduced infarct size over a 20% respect to untreated and NAPSC injected mice, recovered left ventricle ejection fraction (LVEF) similar to healthy controls, and reduced EMMPRIN downstream MMP9 expression. In magnetic resonance scans of mouse hearts 2 days after AMI and injected with NAP9, we detected a significant gadolinium enhancement in the left ventricle respect to non-injected mice and to mice injected with NAPSC. Late gadolinium enhancement assays exhibited NAP9-mediated left ventricle signal enhancement as early as 30 minutes after nanoprobe injection, in which a close correlation between the MRI signal enhancement and left ventricle infarct size was detected. Taken together, these results point EMMPRIN targeted nanoprobes as a new tool for the treatment of AMI.

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