Unilateral vagus nerve stimulation improves ventricular autonomic nerve distribution and functional imbalance in a canine heart failure model.

BACKGROUND Chronic heart failure (HF) is the main complication of various organic heart diseases. An imbalance of the autonomic nervous system has close associations with arrhythmia, ventricular remodeling, and sudden death upon HF. This study investigated whether unilateral vagus nerve stimulation could increase vagal activity, improve autonomic nerve distribution, and cardiac function in a HF model. METHODS Eighteen dogs were randomly divided into 3 groups: sham operation, HF, and HF + vagal stimulation, with 6 dogs per group. The sham operation group had a pacemaker implanted, with no pacing; the HF group was tachypaced at 50 times/min for 37 d to establish the (chronic or congestive) HF model; Vagal stimulation group were implanted with a pacemaker at 250 times/min rapid pacing for 30 d, then the right vagus nerve was stimulated for 7 d (frequency: 20 Hz). Left ventricular ejection fraction (LVEF) and mean arterial pressure (MAP) were examined with an ultrasound diagnostic apparatus. Resting heart rate was recorded with an electrocardiogram monitor. The expression of tyrosine hydroxylase (TH) and choline acetyl-transferase (ChAT) protein was examined by immuno-histochemistry. RESULTS 30 d after rapid ventricular pacing, MAP < 60 mm Hg, and LVEF < 50%, the HF model was successfully established in canines. The results showed that there were no differences in MAP, LVEF, and resting heart rate at baseline in each group (P > 0.05). After 30 d of pacing, MAP and LVEF were reduced and resting heart rate increased in the HF and HF + vagal stimulation group compared to the sham operation group (P < 0.05). After 37 d, compared with the sham operation group, MAP and LVEF were significantly reduced and resting heart rate significantly increased in HF group (P < 0.05). Compared with the sham operation group, TH and ChAT positive nerve density heterogeneity increased in the HF group but did not change in the HF + vagal stimulation group. TH protein expression was increased and ChAT protein expression reduced in the HF group; TH expression decreased and ChAT expression increased in the HF + vagal stimulation group. CONCLUSION Unilateral vagus nerve stimulation increased vagus nerve activity, slowed heart rate, recovered autonomic nerve homogeneity and function imbalance, and improved heart function in HF.