Effects of Vagus Nerve Stimulation Via Cholinergic Anti-Inflammatory Pathway Activation on Myocardial Ischemia/Reperfusion Injury in Canine

Background: Acute myocardial infarction (AMI) was a type of disease with high mortality rate and high disability rate. And about 50% of the final area of myocardial infarction after AMI was led by ischemia/reperfusion (I/R) injury. The I/R injury was a kind of systemic inflammatory response, in which the main performance laid in the release of the large quantity of inflammatory cytokines. The basic experiments, clinical studies and the large scaled epidemiology investigations found that the low functions of vagus nerves had close relevance with the occurrence, development and prognosis of the cardiovascular diseases. This study investigate the effects of cholinergic anti-inflammatory pathway with with vagus never stimulation I/R injury in canine. Methods: 18 adult mongrel dogs were randomly divided into 3 groups (n = 6): sham operation group (sham Group), ischemia/reperfusion group (I/R group), right vagus nerve stimulation and ischemia/reperfusion group (STM group). The hemodynamic indexes were measured after reperfusion 120 min. Through internal jugular venous blood, serum acetylcholine (Ach), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) concentrations were detected by ELISA. Alpha 7 subunit Ach acetylcholine receptor (alpha 7nAchR) expression level was detected with immunohistochemical method. HE staining was used to observe the degree of neutrophil infiltration. Results: After ischemia/reperfusion 120 min, compared with sham group, TNF-alpha and IL-6 were significantly decreased, Ach content increased, the expression of alpha d7nAchR protein was significantly reduced in I/R group (P < 0.05). Expression of alpha 7nAchR protein, Ach content, TNF-alpha and IL-6 level had no significant difference in STM group (P < 0.05). Compared with I/R group, the expression of Ach and alpha 7nAchR protein significantly increased the TNF- and IL-6 levels decreased in STM group (P < 0.05). Compared with the baseline, TNF-alpha and IL-6 levels significantly increased Ach content decreased in I/R group after ischemia/reperfusion 120 min (P < 0.05). Ach, TNF-alpha and IL-6 levels had no significant change in sham group and STM group of (P < 0.05). TNF-alpha and IL-6 were negatively correlated with Ach in I/R group (P < 0.05), and TNF-alpha, IL-6 were negatively correlated with Ach in group STM (P < 0.05). Massive infiltration of neutrophils were detected in myocardial tissue of I/R group, and a small number of neutrophils infiltration were detected in STM group. Conclusion: Right vagus nerve stimulation could activate anti-inflammatory pathway and inhibit the systemic and local inflammatory reaction to relieve myocardial I/R injury.