Low-Level Vagus Nerve Stimulation Attenuates Myocardial Ischemic Reperfusion Injury by Antioxidative Stress and Antiapoptosis Reactions in Canines.

Abstract

Low-level vagus nerve stimulation (LL-VNS) has been demonstrated to protect myocardium against acute ischemia/reperfusion (I/R) injury. However, the underlying mechanism of this protective effect remains unknown. This study aimed to test the hypothesis that LL-VNS exerts cardioprotective effect on acute I/R injury in canines via antioxidative stress and antiapoptosis reactions. Thirty anesthetized mongrel dogs were randomly divided into three groups: I/R group (N = 12, the left anterior descending coronary artery was occluded for 1 hour following by 1 hour reperfusion), LL-VNS group (N = 9, I/R plus LL-VNS), and sham group (N = 9, sham surgery without LL-VNS). The voltage threshold was set at 80% of the voltage required to slow the sinus rate. Infarct size was assessed with Evans Blue and triphenyltetrazolium chloride. Activity assays, TUNEL staining, and western blotting were performed to determine markers of oxidative stress and apoptosis. LL-VNS significantly decreased the incidence of ventricular arrhythmias, increased vagal tone, as confirmed by heart rate viability, and reduced infarct size compared with the I/R group. This improvement was associated with a reduction in myocardial neutrophil infiltration, the inhibition of oxidative stress, and the suppression in cardiomyocyte apoptosis. In contrast, the lack of LL-VNS in the I/R group induced the opposite effect compared with the sham group. LL-VNS exerts protective effects on myocardial I/R injury. Its potential mechanisms involve the suppression of oxidative stress and cellular apoptosis.