Abstract
ObjectivesSpinal cord stimulation (SCS) is an established neuromodulation method that regulates the cardiac autonomic system. However, the biological mechanisms of the therapeutic effects of SCS after myocardial infarction (MI) remain unclear. Materials and MethodsTwenty-five rabbits were divided into five groups: SCS-MI (voltage: 0.5 v; pulse width: 0.2 ms; 50 Hz; ten minutes on and 30 minutes off; two weeks; n = 5), MI (n = 5), sham SCS-MI (voltage: 0 v; two weeks; n = 5), sham MI (n = 5), and blank control (n = 5) groups. MI was induced by permanent left anterior descending artery ligation. SCS-MI and sham SCS-MI rabbits received the corresponding interventions 24 hours after MI. Autonomic remodeling was evaluated using enzyme-linked immunosorbent assay and immunohistochemistry. Inflammation and myocardial fibrosis were assessed using immunohistochemistry, quantitative polymerase chain reaction, hematoxylin and eosin staining, Masson staining, and Western blot. ResultsSCS improved the abnormal systemic autonomic activity. Cardiac norepinephrine decreased after MI (p < 0.01) and did not improve with SCS. Cardiac acetylcholine increased with SCS compared with the MI group (p < 0.05). However, no difference was observed between the MI and blank control groups. Growth-associated protein 43 (p < 0.001) and tyrosine hydroxylase (p < 0.001) increased whereas choline acetyltransferase (p < 0.05) decreased in the MI group compared with the blank control group. These changes were attenuated with SCS. SCS inhibited inflammation, decreased the ratio of phosphorylated-Erk to Erk (p < 0.001), and increased the ratio of phosphorylated-STAT3 to STAT3 (p < 0.001) compared with the MI group. Myocardial fibrosis was also attenuated by SCS. ConclusionsSCS improved abnormal autonomic activity after MI, leading to reduced inflammation, reactivation of STAT3, and inhibition of Erk. Additionally, SCS attenuated myocardial fibrosis. Our results warrant future studies of biological mechanisms of the therapeutic effects of SCS after MI.
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