Remodeling of cardiac sympathetic innervation with thoracic spinal cord simulation improves left ventricular function in a porcine model of ischemic cardiomyopathy

Abstract

Background: Prior studies demonstrate that thoracic spinal cord stimulation (SCS) improves left ventricular (LV) function in heart failure (HF), nevertheless, the mechanism of action remains unknown. Methods and results: We performed chronic thoracic SCS (50Hz, pulse width 0.2ms) using two octrode leads implanted targeting along the midline and the left side at T1-3 levels in 30 adult pigs with ischemic HF induced by myocardial infarction and rapid ventricular pacing for 4 wks. All animals were treated with daily oral metoprolol succinate (25mg) plus ramipril (2.5mg), and randomized into control group (n=10), intermittent SCS (4 hrs x 3, n=10) or continuous SCS (24 hrs, n=10) for 10 weeks. Detail immunohistological studies on myocardial sympathetic (tyrosine hydroxylase [TH]) and parasympathetic (acetylcholinase [Ach]) nerve spouting (growth-associated protein43 [GAP-43]) and nerve innervation (protein gene product 9.5 [PGP9.5] were performed at infarct, peri-infarct and normal regions. Both continuous and intermittent SCS significantly improved LV ejection fraction at 10 wks compared with controls (P<0.05). There was no significant difference in pattern of the Ach staining over different regions between 3 groups. However, SCS-treated groups showed diffuse sympathetic nerve spouting over the infarct, peri-infarct and normal regions rather than only in the peri-infarct and infarct regions in controls (Figure). Moreover, sympathetic innervation was decreased at the peri-infarct and infarct regions in controls, but was increased at peri-infarct and infarct regions after SCS (Figure). Conclusions: In porcine model of ischemic HF, SCS induce significant remodeling of cardiac sympathetic nerve innervation over peri-infarct and infarct regions which is associated with improvement of LV function.