Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure

Song Yan Liao, Yuan Liu, Mingliang Zuo, Yuelin Zhang, Wensheng Yue, Ka Wing Au, Wing Hon Lai, Yangsong Wu, Chika Shuto, Peter Chen, Chung Wah Siu, Peter J. Schwartz, Hung Fat Tse

Research output: Contribution to journalArticle

Abstract

Aims Thoracic spinal cord stimulation (SCS) has been shown to improve left ventricular ejection fraction (LVEF) in heart failure (HF). Nevertheless, the optimal duration (intermittent vs. continuous) of stimulation and the mechanisms of action remain unclear. Methods and results We performed chronic thoracic SCS at the level of T1-T3 (50 Hz, pulse width 0.2 ms) in 30 adult pigs with HF induced by myocardial infarction and rapid ventricular pacing for 4 weeks. All the animals were treated with daily oral metoprolol succinate (25 mg) plus ramipril (2.5 mg), and randomized to a control group (n = 10), intermittent SCS (4 h ×3, n = 10) or continuous SCS (24 h, n = 10) for 10 weeks. Serial measurements of LVEF and +dP/dt and serum levels of norepinephrine and B-type natriuretic peptide (BNP) were measured. After sacrifice, immunohistological studies of myocardial sympathetic and parasympathetic nerve sprouting and innervation were performed. Echocardiogram revealed a significant increase in LVEF and +dP/dt at 10 weeks in both the intermittent and continuous SCS group compared with controls (P <0.05). In both SCS groups, there was diffuse sympathetic nerve sprouting over the infarct, peri-infarct, and normal regions compared with only the peri-infarct and infarct regions in the control group. In addition, sympathetic innervation at the peri-infarct and infarct regions was increased following SCS, but decreased in the control group. Myocardium norepinephrine spillover and serum BNP at 10 weeks was significantly decreased only in the continuous SCS group (P <0.05). Conclusions In a porcine model of HF, SCS induces significant remodelling of cardiac sympathetic innervation over the peri-infarct and infarct regions and is associated with improved LV function and reduced myocardial norepinephrine spillover.

Original languageEnglish
Pages (from-to)1875-1883
Number of pages9
JournalEuropace
Volume17
Issue number12
DOIs
Publication statusPublished - Nov 10 2015

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Keywords

  • Heart failure
  • Spinal cord stimulation
  • Sympathetic innervation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Liao, S. Y., Liu, Y., Zuo, M., Zhang, Y., Yue, W., Au, K. W., Lai, W. H., Wu, Y., Shuto, C., Chen, P., Siu, C. W., Schwartz, P. J., & Tse, H. F. (2015). Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure. Europace, 17(12), 1875-1883. https://doi.org/10.1093/europace/euu409