Control/Tracking Number: 06-A-335172-ACC


Chronic Therapy with Selective Electric Vagus Nerve Stimulation Normalizes Plasma Concentration of Tissue Necrosis Factor-α, Interleukin-6 and B-Type Natriuretic Peptide in Dogs with Heart Failure


Author Block: Ramesh C. Gupta, Makoto Imai, Alice J. Jiang, Mengjun Wang, Hani N. Sabbah, Henry Ford Health System, Detroit, MI


Background: Plasma concentration of the cytokines interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and of B-type natriuretic peptide is elevated in patients with heart failure (HF) and serve as biomarkers of worsening HF. We showed that chronic (3 months) therapy with selective electric Vagus nerve stimulation (VNS) (CardioFitTM, BioControl Medical, Ltd.), improves LV function and attenuates LV remodeling in dogs with microembolization-induced HF. This study examined the effects of chronic VNS therapy on plasma concentration of TNFα, IL-6, and n-terminal-proBNP (nt-proBNP) in the same dogs. Methods: Peripheral blood samples were collected asceptically in EDTA-treated tubes from 7 HF VNS-treated dogs, 6 sham-operated untreated HF dogs and 6 normal (NL) dogs. All blood samples were obtained from concious dogs at the end of 3 months of therapy or follow-up. TNFα, IL-6 and nt-proBNP were quantified in plasma using a colorimetric immunoassay kit specific for each of the 3 biomarkers and the results expressed as pg/ml. Results: Data are shown in the table. The levels of IL-6, TNFα, and NT-proBNP in plasma increased significantly in untreated HF dogs compared to NL. Three months treatment with VNS normalized the levels of all three biomarkers. Conclusions: Chronic VNS therapy with CardioFitTM normalizes cytokines level and nt-proBNP in plasma of dogs with HF. This finding is consistent with the observed improvement in LV function and remodeling seen in dogs with HF after chronic VNS therapy.

IL-6, TNFα, and nt-proBNP Plasma Levels (pg/ml)

 

NL

HF-Untreated

HF + VNS

TNFα

9 ± 1

59 ± 11*

14 ± 1**

IL-6

5 ± 1

47 ± 6*

16 ± 3**

nt-proBNP

230 ± 18

554 ± 84*

260 ± 24**

*=p<0.05 vs. NL; **=p<0.05 vs. HF-Untreated

 

Presented, 55th Annual Scientific Session of the American College of Cardiology, Atlanta, GA, March 11-14, 2006.

Published:  J Am Coll Cardiol 47:77A, 2006.