Abstract

Introduction: Vagus nerve stimulation (VNS) attenuates left ventricular remodeling after myocardial infarction (MI) by improving the imbalance of autonomic nervous system. Our previous study found Low-level tragus stimulation (LL-TS) had the same antiarrhythmic effects as VNS by regulation of the autonomic nervous system. Hypothesis: Chronic intermittent LL-TS could attenuate left ventricular remodeling in conscious dogs with healed myocardial infarction. Methods: Thirty beagle dogs were randomly divided into three groups. LL-TS group (n=10) and MI group (n=10) underwent left anterior descending coronary artery and all major diagonal branches ligation to introduce MI under general anesthesia. Control group (n=10) underwent sham surgery. Auricular vagus nerve stimulation (frequency 20Hz, pulse width 1ms) with duty cycle of 5s on and 5s off was delivered to the bilateral tragus in external auditory canal with ear-clips connected to a custom-made stimulator. The voltage slowing sinus rate was used as the threshold for setting LL-TS at 80% below that. The actual voltage of stimulation was in the range of 16 to 24V that did not cause any heart rate changes. LL-TS group was given four hours of LL-TS at 7-9AM and 4-6PM on conscious dogs from the day of MI introduction to the end of 90-day follow-up, MI group and control group were given no stimulations. Results: At the end of 90-days follow-up LL-TS group significantly reduced left ventricular dilatation, improve left ventricular contractile and diastolic function, reduced mean infarct size by about 50% compared with MI group. Also LL-TS treatment alleviated cardiac fibrosis around infarction border and significantly decreased protein level of collagen I, collagen III, TGF-β1, MMP-9 in noninfarcted left ventricular free wall tissue after MI. Moreover, the plasma level of hs-CRP, NE and NT-proBNP in LL-TS group was significantly lower than MI group from the 7th day to the end of follow-up. Conclusions: Chronic intermittent low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve can attenuate left ventricular remodeling and improve cardiac function in conscious dogs with healed myocardial infarction.

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