title: Remodelling of cardiac sympathetic re-innervation with thoracic spinal cord stimulation improves left ventricular function in a porcine model of heart failure.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Song-Yan
authors.initials: SY
authors.lastname: Liao
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Zuo
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yue
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Ka-Wing
authors.initials: KW
authors.lastname: Au
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Wing-Hon
authors.initials: WH
authors.lastname: Lai
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Yangsong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Center for Innovation and Strategic Collaboration, St Jude Medical, Inc, St Paul, MN, USA.
authors.forename: Chika
authors.initials: C
authors.lastname: Shuto
authors.affiliation: Center for Innovation and Strategic Collaboration, St Jude Medical, Inc, St Paul, MN, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Chen
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China Research Center of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.affiliation: IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
authors.affiliation: Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China Research Center of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China Shenzhen Institutes of Research and Innovation, University of Hong Kong, Hong Kong, China hftse@hkucc.hku.hk.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009416:Nerve Regeneration; D009638:Norepinephrine / Q000097:blood; D011897:Random Allocation; D020127:Recovery of Function; D062187:Spinal Cord Stimulation / Q000379:methods*; D013318:Stroke Volume; D013552:Swine; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013904:Thoracic Vertebrae; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain; D009638:Norepinephrine
keywords: Heart failure; Spinal cord stimulation; Sympathetic innervation