Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure

Figures

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  Figure 1. The calculation of left ventricular ejection fraction. Left ventricular ejection fraction was calculated using the biplane Simpson method. See text for details. A, The apical 4‐chamber views at the end of diastole (left panel) and systole (right panel). B, The apical 2‐chamber views at the end of diastole (left panel) and systole (right panel). BPM indicates beats per minute.

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  Figure 2. Renal tissue catecholamine in left atrial appendage. A, The adrenaline content of renal tissue extracts. B, The norepinephrine content of renal tissue extracts. C, The dopamine content of renal tissue extracts. # P<0.05 and ## P<0.01. HF indicates heart failure; RDN, renal denervation.

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  Figure 3. Electrophysiology study in LAA. A, ERPs among 3 groups. Left panel shows ERP at basic cycle lengths of 300 ms. Middle panel shows ERP at basic cycle lengths of 250 ms. Right panel shows ERP at basic cycle lengths of 200 ms. B, An example of MAP during a pacing cycle length of 300 ms among 3 groups. C, APD 90 at pacing cycle lengths of 300 and 250 ms. APD 90 indicates the action potential duration measured from the steepest deflection of the slope of phase 0 of the MAP to the time of 90% repolarization. D, Inducibility of AF. *P<0.05 and **P<0.01 (vs control) and # P<0.05 and ## P<0.01 (vs HF‐RDN). AF indicates atrial fibrillation; APD, action potential duration; ERP, effective refractory period; HF, heart failure; LAA, left atrial appendage; MAP, monophasic action potential; RDN, renal denervation.

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  Figure 4. Myocardial apoptosis in left atrial appendage. A, Protein expression of cleaved caspase 3 and caspase 3 in each group by Western blot analysis. B, The ratio of cleaved caspase 3 to caspase 3 was evaluated in each group. *P<0.05 (vs control) and # P<0.05 (vs HF‐RDN). RDN sham indicates HF rabbit with open abdomen surgery without RDN. HF indicates heart failure; RDN, renal denervation.

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  Figure 5. Atrial tissue fibrosis detected by Masson's trichrome staining in LAA. A, An example of atrial fibrosis in control rabbits. B, An example of atrial fibrosis in HF rabbits. C, An example of atrial fibrosis in HF‐RDN rabbits. D, Quantitative analysis of fibrotic area in the LAA among all groups. **P<0.01 (vs control) and ## P<0.01 (vs HF‐RDN). The collagen area was calculated as a percentage of the total LAA area. HF indicates heart failure; LAA, left atrial appendage; RDN, renal denervation.

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  Figure 6. Immunohistochemistry staining of tyrosine hydroxylase in LAA. A, Control rabbits LAA. B, HF rabbits LAA, C, HF‐RDN rabbits LAA. D, The percentage of the tyrosine hydroxylase–positive portions in LAA among 3 groups. *P<0.05 and **P<0.01 (vs control) and ## P<0.01 (vs HF‐RDN). HF indicates heart failure; LAA, left atrial appendage; RDN, renal denervation.

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  Figure 7. Immunohistochemistry staining of TGF‐β in LAA. A, Control rabbits LAA. B, HF rabbits LAA. C, HF‐RDN rabbits LAA. D, The percentage of the TGF‐β‐positive portions in LAA among 3 groups. **P<0.01 and ***P<0.001 (vs control) and ### P<0.001 (vs HF‐RDN). HF indicates heart failure; LAA, left atrial appendage; RDN, renal denervation; TGF‐β, transforming growth factor‐β.

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  Figure 8. Expression of Cav1.2, Nav1.5, Kir2.1, and KvLQT1 in LAA. Messenger RNA expression of Cav1.2, Nav1.5, Kir2.1, and KvLQT1 as determined by real‐time polymerase chain reaction. *P<0.05 and **P<0.01 (vs control), and # P<0.05 and ## P<0.01 (vs heart failure–renal denervation). HF indicates heart failure; LAA, left atrial appendage; RDN, renal denervation.

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  Figure 9. Expression of phosphoinositide 3‐kinase (PI3K), AKT, and endothelial nitric oxide synthase (eNOS) in left atrial appendage. mRNA expression of PI3K, AKT, and eNOS as determined by real‐time polymerase chain reaction. *P<0.05 (vs control), and ## P<0.01 (vs heart failure–renal denervation). HF indicates heart failure; RDN, renal denervation.