Basic/Translational Science -> Whole Animal Electrophysiology and Pharmacology (includes Neurohumoral Modulation) D-AB19 - Basic Science: What Lies Beneath (ID 20) Abstract

D-AB19-03 - Transcutaneous Vagus Nerve Stimulation Ameliorates The Phenotype Of Heart Failure With Preserved Ejection Fraction Through Its Anti-inflammatory Effects (ID 1442)

 K. Elkholey: Nothing relevant to disclose.


Background: Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for 50% of HF. Inflammation and left ventricular (LV) fibrosis play an important role in the development of HFpEF.
Objective: We have previously shown that low level transcutaneous vagus nerve stimulation (LLTS) is antiarrhythmic and anti-inflammatory. We examined the effects of chronic, intermittent LLTS on inflammation, fibrosis and diastolic dysfunction in a rat model of HFpEF.
Methods: Dahl salt sensitive (DS) rats of either sex were randomized into high salt (HS, 8% NaCl) or low salt (LS; n=23) diet (0.3% NaCl) at 7 weeks of age. After 6 weeks of HS diets, HS rats were randomized into 3 groups: active LLTS (n=37), sham LLTS (n=38) and LLTS plus methyllycaconitine (MLA) (n=31), a blocker of the α7-nicotinic acetylcholine receptor (a7nAChR), which mediates the anti-inflammatory effects of LLTS. Stimulation was delivered for 30min daily (20Hz, 3mA) for 4 weeks. ECG and echocardiogram were performed at 13 weeks (baseline) and 17 weeks (endpoint).
Results: HS rats developed significant hypertension and signs of HFpEF, while 24% of females and 53% of males died (P=0.004). There was no difference in LV ejection fraction among the groups. Systolic and diastolic blood pressure (BP) were elevated in the HS groups compared to LS group (133±25mmHg) at endpoint, but the BP elevation was attenuated in the active LLTS group (159±30mmHg), compared to both LLTS sham (177±24mmHg; p=0.003) and LLTS active plus MLA groups (171±29mmHg; p=0.01). Echocardiographic parameters, including e’ and circumferential strain showed a similar amelioration in the presence of active LLTS compared to sham LLTS and this effect was attenuated in the presence of MLA. Left ventricular fibrosis was significantly decreased in active LLTS rats (1.8±1.1%) compared to sham LLTS rats (4.1±1.2%; p=0.001). This effect was attenuated in the presence of MLA (4.2±1.3%), suggesting that the anti-inflammatory effect of LLTS is necessary to prevent fibrosis in this model.
Conclusion: Autonomic modulation with LLTS attenuates LV fibrosis and echocardiographic parameters induced by HS diet through its anti-inflammatory effects. These results provide the basis for the examining the role of LLTS in patients with HFpEF.