Electroacupuncture at PC6 mediates cardioprotection by vagal afferent-sympathetic efferent anti-inflammatory pathway in myocardial infarction mouse.

Abstract

AIMS: This study aimed to elucidate the autonomic pathways underlying the cardioprotective effect of electroacupuncture (EA) at Neiguan (PC6) after myocardial infarction (MI). Specifically, we investigated whether these protective effects are mediated through a sympathetic efferent anti-inflammatory pathway, rather than the classical vagal efferent anti-inflammatory pathways. METHODS AND RESULTS: In a mouse MI model, EA intervention was combined with surgical and pharmacological manipulations, including right cervical vagotomy, splenectomy, adrenalectomy, and peripheral sympathetic blockade. Unilateral (left or right) and bilateral EA stimulations at PC6 were applied to characterize the side-specific involvement of vagal afferent fibers. Cardiac function was assessed via M-mode echocardiography, infarct size was measured using TTC staining, and macrophage infiltration and M2 polarization in infarcted myocardium were analyzed by flow cytometry. EA markedly reduced infarct size and improved cardiac function, as evidenced by increased left ventricular ejection fraction and fractional shortening. Concurrently, EA alleviated excessive macrophage accumulation in the infarcted myocardium and promoted M2 macrophage polarization, accompanied by elevated IL-10 levels that positively correlated with the proportion of M2 macrophages. Right cervical vagotomy completely abrogated the cardioprotective effects of right-sided EA (due to total blockade of afferent input), while left sided and bilateral EA remained effective, indicating that the vagal afferent signaling is the primary vagal component mediating EA's effects. Furthermore, neither splenectomy nor adrenalectomy weakened EA's beneficial effects on cardiac function or its promotion of M2 polarization, ruling out the classical vagal-splenic and vagal-adrenal reflexes as the principal mediating pathways. In contrast, chemical blockade of peripheral sympathetic activity abolished these cardioprotective and immunomodulatory benefits of EA, demonstrating that intact sympathetic signaling is essential for EA-mediated cardioprotection and macrophage polarization after MI. CONCLUSION: Our findings demonstrate that EA at PC6 improves cardiac function after MI by promoting M2 polarization of cardiac macrophages, predominantly through a vagal afferent-sympathetic efferent neuroimmune pathway, whereas the classical vagal-splenic and vagal-adrenal pathways are not required.