Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model

John C. Lopshire, Xiaohong Zhou, Cristian Dusa, Takeshi Ueyama, Joshua Rosenberger, Nicole Courtney, Michael Ujhelyi, Thomas Mullen, Mithilesh Das, Douglas P. Zipes

Research output: Contribution to journalArticle

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Abstract

BACKGROUND - Spinal cord stimulation (SCS) reduces the incidence of ventricular tachyarrhythmias in experimental models. This study investigated the effects of long-term SCS on ventricular function in a postinfarction canine heart failure model. METHODS AND RESULTS - In stage 1, dogs underwent implantable cardioverter-defibrillator implantation and embolization of the left anterior descending artery followed by right ventricular pacing (240 ppm) for 3 weeks to produce heart failure. In stage 2, 28 surviving animals were assigned to the SCS (delivered at the T4/T5 spinal region for 2 hours 3 times a day), medicine (MED; carvedilol therapy at 12.5 mg PO BID), or control (CTRL; no therapy) group for the initial phase 1 study. In a subsequent phase 2 study, 32 stage 1 survivors were equally randomized to the SCS, MEDS (carvedilol plus ramipril 2.5 mg PO QD), SCS plus MEDS (concurrent therapy), or CTRL group. Animals were monitored for 5 weeks (phase 1) or 10 weeks (phase 2). In stage 3, all phase 1 animals underwent circumflex artery balloon occlusion for 1 hour. In the SCS group, left ventricular ejection fraction was 65±5% at baseline, 17±3% at the end of stage 1, and 47±7% at the end of stage 2. In the MED group, left ventricular ejection fraction was 61±4% at baseline, 18±3% at the end of stage 1, and 34±4% at the end of stage 2. In the CTRL group, left ventricular ejection fraction was 64±5% at baseline, 19±5% at the end of stage 1, and 28±3% at the end of stage 2. Left ventricular ejection fraction was significantly improved in the SCS compared with the MED and CTRL groups (P<0.001 for both). The mean number of spontaneous nonsustained ventricular tachyarrhythmias during stage 2 and the occurrence of ischemic ventricular tachyarrhythmias during stage 3 also were significantly decreased in the SCS (27±17 and 27%, respectively; P<0.03) and MED (58±42 and 33%; P<0.05) versus CTRL (88±52 and 76%) group. After 10 weeks in the phase 2 studies, the greatest recovery in ejection fraction was noted in the SCS (52±5%) and SCS+MEDS (46±4%) groups compared with the MEDS (38±2%) and CTRL (31±4%) groups. CONCLUSIONS - SCS significantly improved cardiac contractile function and decreased ventricular arrhythmias in canine heart failure.

Original languageEnglish
Pages (from-to)286-294
Number of pages9
JournalCirculation
Volume120
Issue number4
DOIs
StatePublished - Jul 2009

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Spinal Cord Stimulation
Ventricular Function
Canidae
Cardiac Arrhythmias
Heart Failure
Stroke Volume
Tachycardia
Arteries
Ramipril
Balloon Occlusion
Implantable Defibrillators
Group Psychotherapy

Keywords

  • Arrhythmia
  • Death, sudden
  • Heart failure
  • Nervous system, autonomic
  • Tachyarrhythmias

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model. / Lopshire, John C.; Zhou, Xiaohong; Dusa, Cristian; Ueyama, Takeshi; Rosenberger, Joshua; Courtney, Nicole; Ujhelyi, Michael; Mullen, Thomas; Das, Mithilesh; Zipes, Douglas P.

In: Circulation, Vol. 120, No. 4, 07.2009, p. 286-294.

Research output: Contribution to journalArticle

Lopshire, JC, Zhou, X, Dusa, C, Ueyama, T, Rosenberger, J, Courtney, N, Ujhelyi, M, Mullen, T, Das, M & Zipes, DP 2009, 'Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model', Circulation, vol. 120, no. 4, pp. 286-294. https://doi.org/10.1161/CIRCULATIONAHA.108.812412
Lopshire, John C. ; Zhou, Xiaohong ; Dusa, Cristian ; Ueyama, Takeshi ; Rosenberger, Joshua ; Courtney, Nicole ; Ujhelyi, Michael ; Mullen, Thomas ; Das, Mithilesh ; Zipes, Douglas P. / Spinal cord stimulation improves ventricular function and reduces ventricular arrhythmias in a canine postinfarction heart failure model. In: Circulation. 2009 ; Vol. 120, No. 4. pp. 286-294.
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AU - Lopshire, John C.

AU - Zhou, Xiaohong

AU - Dusa, Cristian

AU - Ueyama, Takeshi

AU - Rosenberger, Joshua

AU - Courtney, Nicole

AU - Ujhelyi, Michael

AU - Mullen, Thomas

AU - Das, Mithilesh

AU - Zipes, Douglas P.

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N2 - BACKGROUND - Spinal cord stimulation (SCS) reduces the incidence of ventricular tachyarrhythmias in experimental models. This study investigated the effects of long-term SCS on ventricular function in a postinfarction canine heart failure model. METHODS AND RESULTS - In stage 1, dogs underwent implantable cardioverter-defibrillator implantation and embolization of the left anterior descending artery followed by right ventricular pacing (240 ppm) for 3 weeks to produce heart failure. In stage 2, 28 surviving animals were assigned to the SCS (delivered at the T4/T5 spinal region for 2 hours 3 times a day), medicine (MED; carvedilol therapy at 12.5 mg PO BID), or control (CTRL; no therapy) group for the initial phase 1 study. In a subsequent phase 2 study, 32 stage 1 survivors were equally randomized to the SCS, MEDS (carvedilol plus ramipril 2.5 mg PO QD), SCS plus MEDS (concurrent therapy), or CTRL group. Animals were monitored for 5 weeks (phase 1) or 10 weeks (phase 2). In stage 3, all phase 1 animals underwent circumflex artery balloon occlusion for 1 hour. In the SCS group, left ventricular ejection fraction was 65±5% at baseline, 17±3% at the end of stage 1, and 47±7% at the end of stage 2. In the MED group, left ventricular ejection fraction was 61±4% at baseline, 18±3% at the end of stage 1, and 34±4% at the end of stage 2. In the CTRL group, left ventricular ejection fraction was 64±5% at baseline, 19±5% at the end of stage 1, and 28±3% at the end of stage 2. Left ventricular ejection fraction was significantly improved in the SCS compared with the MED and CTRL groups (P<0.001 for both). The mean number of spontaneous nonsustained ventricular tachyarrhythmias during stage 2 and the occurrence of ischemic ventricular tachyarrhythmias during stage 3 also were significantly decreased in the SCS (27±17 and 27%, respectively; P<0.03) and MED (58±42 and 33%; P<0.05) versus CTRL (88±52 and 76%) group. After 10 weeks in the phase 2 studies, the greatest recovery in ejection fraction was noted in the SCS (52±5%) and SCS+MEDS (46±4%) groups compared with the MEDS (38±2%) and CTRL (31±4%) groups. CONCLUSIONS - SCS significantly improved cardiac contractile function and decreased ventricular arrhythmias in canine heart failure.

AB - BACKGROUND - Spinal cord stimulation (SCS) reduces the incidence of ventricular tachyarrhythmias in experimental models. This study investigated the effects of long-term SCS on ventricular function in a postinfarction canine heart failure model. METHODS AND RESULTS - In stage 1, dogs underwent implantable cardioverter-defibrillator implantation and embolization of the left anterior descending artery followed by right ventricular pacing (240 ppm) for 3 weeks to produce heart failure. In stage 2, 28 surviving animals were assigned to the SCS (delivered at the T4/T5 spinal region for 2 hours 3 times a day), medicine (MED; carvedilol therapy at 12.5 mg PO BID), or control (CTRL; no therapy) group for the initial phase 1 study. In a subsequent phase 2 study, 32 stage 1 survivors were equally randomized to the SCS, MEDS (carvedilol plus ramipril 2.5 mg PO QD), SCS plus MEDS (concurrent therapy), or CTRL group. Animals were monitored for 5 weeks (phase 1) or 10 weeks (phase 2). In stage 3, all phase 1 animals underwent circumflex artery balloon occlusion for 1 hour. In the SCS group, left ventricular ejection fraction was 65±5% at baseline, 17±3% at the end of stage 1, and 47±7% at the end of stage 2. In the MED group, left ventricular ejection fraction was 61±4% at baseline, 18±3% at the end of stage 1, and 34±4% at the end of stage 2. In the CTRL group, left ventricular ejection fraction was 64±5% at baseline, 19±5% at the end of stage 1, and 28±3% at the end of stage 2. Left ventricular ejection fraction was significantly improved in the SCS compared with the MED and CTRL groups (P<0.001 for both). The mean number of spontaneous nonsustained ventricular tachyarrhythmias during stage 2 and the occurrence of ischemic ventricular tachyarrhythmias during stage 3 also were significantly decreased in the SCS (27±17 and 27%, respectively; P<0.03) and MED (58±42 and 33%; P<0.05) versus CTRL (88±52 and 76%) group. After 10 weeks in the phase 2 studies, the greatest recovery in ejection fraction was noted in the SCS (52±5%) and SCS+MEDS (46±4%) groups compared with the MEDS (38±2%) and CTRL (31±4%) groups. CONCLUSIONS - SCS significantly improved cardiac contractile function and decreased ventricular arrhythmias in canine heart failure.

KW - Arrhythmia

KW - Death, sudden

KW - Heart failure

KW - Nervous system, autonomic

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