Interaction between Endothelin-1 and Left Stellate Ganglion Activation: A Potential Mechanism of Malignant Ventricular Arrhythmia during Myocardial Ischemia

Figures

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  Figure 1. Local ET-1 microinjection increased ventricular electrophysiological instability in the normal hearts. (a) Schematic representation of the electrode position in the left ventricular free walls. (b) Representative ECG during ERP detection. (c–e) The effects of local ET-1 microinjection on ventricular ERP in the normal hearts. ∗p < 0.05. ERP: effective refractory period; LAA: left atrial appendage; RA: right atrium; RAA: right atrial appendage; RV: right ventricle; LV: left ventricle; LVA: left ventricular apex; LVB: left ventricular base; LVM: median area between the LVA and LVB.

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  Figure 2. Local ET-1 microinjection increased LSG function. (a) Representative blood pressure (BP) elevation in response to LSG electrical stimulation. (b) The effects of ET-1 on LSG function in the two groups. ∗p < 0.05. BP: blood pressure.

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  Figure 3. Local ET-1 microinjection increased LSG activity. (a) Representative schematic of spontaneous LSG spikes. (b) Quantification of the frequency and amplitude of LSG neural spikes. ∗p < 0.05. LADO: left anterior descending occlusion.

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  Figure 4. Local ET-1 microinjection increased the incidence of VT/VF in the ischemic hearts. (a) Representative ECG of ischemia-induced VT/VF. (b) The effects of local ET-1 microinjection on the incidence of VT/VF in the ischemic hearts. ∗p < 0.05. VT: ventricular tachycardia; VF: ventricular fibrillation.

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  Figure 5. Local ET-1 microinjection increased the inflammatory response in the LSG. (a) Representative image of HE staining. (b–d) The effects of local ET-1 microinjection on the expression levels of IL-1β, IL-6, and TNF-α. ∗p < 0.05.

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  Figure 6. Local ET-1 microinjection increased the expression of c-fos and NGF in the LSG. (a) Double staining of c-fos (red) and TH (green) to indicate the activation of sympathetic neurons. (b) Quantitative analysis of the expression of c-fos in the LSG in different groups. (c) Representative image of simple NGF staining. (d) Quantitative analysis of the expression of NGF in the LSG in different groups. ∗p < 0.05. TH: tyrosine hydroxylase; NGF: nerve growth factor.

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  Figure 7. Local ET-1 microinjection activates the PI3K/Akt/GSK-3β pathway in the LSG. (a) Representative images showing double-immunofluorescence staining for ETA-R (red) and TH (green) in the LSG. (b) Representative images of the Western blots. (c–e) Quantitative analyses of the Western blot results showed that the ETA-R and PI3K/Akt/GSK-3β pathways were activated in the LSG. ∗p < 0.05. ETA-R: ETA receptor; TH: tyrosine hydroxylase.

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  Figure 8. Schematic diagram depicting the potential role of ET-1 in the LSG and the aggravation of VA. ET-1 is mainly synthesized by vascular endothelial cells and contributes to cardiac sympathetic hyperactivity, aggravating LADO-induced VA. The underlying mechanisms may be correlated directly with activated ETA-R signaling in the LSG or correlated indirectly with an increased inflammatory response.