Early suppression of the excessive inflammatory response may attribute to the beneficial effect of vagal nerve stimulation on chronic heart failure

Background: The inflammatory response plays a pivotal role in the pathogenesis of chronic heart failure (CHF). Although vagal nerve stimulation (VNS) improves CHF independent of heart rate reduction, the mechanism that benefits CHF remains unclear. Since VNS exerts the powerful anti-inflammatory effect, we investigated how VNS impacts on the inflammation in the development of CHF after large myocardial infarction (MI) in rats. Methods: In 8 weeks Sprague–Dawley rats, we created large myocardial infarction (MI) and started VNS 2 weeks after MI (CHF: n = 8, VNS: n = 13). We adjusted the intensity of VNS (20Hz) below the level to induce bradycardia. To elucidate the pure impact of VNS on inflammation, we evaluated systemic (blood) and local (heart) inflammatory markers at 3 days after the initiation of VNS. Results: At 3 days, VNS change neither hemodynamic parameters nor plasma BNP as an index of CHF. VNS significantly reduced the invasion of CD 68 positive cells (CHF: 295.1 ± 142.1, VNS: 110.7 ± 59.6 counts/mm², p < 0.01) and decreased MCP-1 in the left ventricle (LV). In addition, VNS markedly reduced interleukin-1β (IL-1β) in plasma (CHF: 75.7 ± 27.6, VNS: 32.9 ± 6.8 pg/mL, p < 0.01) and heart (CHF: 13.2 ± 4.6, VNS: 9.3 ± 2.4 pg/mg, p < 0.05). TNF-α and IL-6 remained unchanged between two groups. Conclusion: VNS significant attenuates IL-1β production and the invasion of inflammatory cells prior to the improvement of hemodynamics. Early suppression of the excessive inflammatory response may attribute to the beneficial effect of VNS on CHF in the long-term.