1. Spinal Cord Stimulation Decreases Ventricular Arrhythmogenicity During Acute Myocardial Ischemia
Kimberly Howard-Quijano MD MS, Tatsuo Takamiya MD, Yukiko Kubo MD, Erica A. Dale PhD, Wei Zhou PhD, Jasmine Kipke BS, Aman Mahajan MD PhD
Department of Anesthesiology and Perioperative Medicine
David Geffen School of Medicine, UCLA

2. Disclosures None Funding FAER Mentored Basic Science Award
SCD, due to ventricular arrhythmia..causing 400,000 deaths per year. Increased sympathetic output leads to increased ventricular arrhythmias
Modulation = thoracic epidurals and surgical stellate ganglionectomy
However, the control of sympathetic output at the level of the spinal cord is not well understoon.

3. Introduction
Sudden cardiac death due to ventricular arrhythmias is the leading cause of mortality in the United States
Autonomic nervous system imbalance is a contributor to the pathophysiology of lethal arrhythmias.
Myocardial ischemia induces increase in sympathetic tone
SCD, due to ventricular arrhythmia..causing 400,000 deaths per year. Increased sympathetic output leads to increased ventricular arrhythmias
Modulation = thoracic epidurals and surgical stellate ganglionectomy
However, the control of sympathetic output at the level of the spinal cord is not well understoon.

4. Introduction
Neuraxial interventions at the spinal level, including TEA and spinal cord stimulation (SCS) show therapeutic benefit in control of cardiac arrhythmias.
While regulation of myocardial excitability in cardiac tissues is understood, there are major gaps in our understanding of the mechanism of sympathetic neural control of cardiac excitability.
SCD, due to ventricular arrhythmia..causing 400,000 deaths per year
Increased sympathetic output leads to increased ventricular arrhythmias
Modulation = thoracic epidurals and surgical stellate ganglionectomy
However, the control of sympathetic output at the level of the spinal cord is not well understoon.

5. SCD, due to ventricular arrhythmia..causing 400,000 deaths per year
Increased sympathetic output leads to increased ventricular arrhythmias
Modulation = thoracic epidurals and surgical stellate ganglionectomy
However, the control of sympathetic output at the level of the spinal cord is not well understoon.

6. Introduction
The aim of this study is to investigate the effect of SCS on ventricular electrophysiology during myocardial ischemia in order to better understand the mechanism of SCS’s therapeutic benefit
We hypothesize that SCS decreases ventricular excitability in acute ischemia through reduction in afferent neural signaling and attenuation of spinal cord sympathetic efferent outflow.
Previously we have shown that interruption of afferent neural input to the spinal cord through dorsal root transection leads to modulation of efferent sympathetic output.

7. Methods 56-electrode sock recorded epicardial electrograms
Yorkshire pigs (n=20, 41 ± 4 kg)
4 pole spinal cord stimulating lead placed in epidural space at T1-T4 with Fluoro guidance
Surgical exposure of the heart
56-electrode sock recorded epicardial electrograms
SCS Lead

8. Methods Animals randomized to SCS or Sham
SCS/Sham for 30 min pre-ischemia
SCS: 50 Hz at 200μsec duration, current intensity of 90% motor threshold
Ischemia induced by 300 sec ligation at 2nd diagonal branch of LAD coronary artery
LAD ligation
Stellate ganglion stimulation increases sympathetic efferent signaling to the heart,- this is a validated model of ventricular arrythmogenesis and sympathoexcitability. The degree of sympathoexcitability is assessed using measures of ARI and dispersion of repolarizatin
Electrophysiologic (EP) measures recorded: baseline, after SCS, during acute ischemia, and reperfusion: in ischemic vs. non-ischemic zones

9. EP Measures Sympathetic stimulation EP Measures Reduction in ARI
Reduction in RT
Increase HRV
Risk Arrhythmias
Increase in Dispersion
Increase in Tp-Te
EP Measures
Activation time (AT)
Repolarization time (RT)
Activation recovery interval (ARI)
Dispersion of repolarization
Tpeak – Tend (Tp-Te)
Heart Rate Variability (HRV)
ARI is a surrogate for action potential duration - ARI is time measured from most negative deflection of dV/dT of the activation wave and the most positive deflection of dV/dT of repolarization wave.
Sympathetic Stimulation = Shortened ARI duration and Increased dispersion of repolarization

10. Effect of SCS on Baseline Cardiac EP
Sham
There was no change in AT, RT, ARI or dispersion. However HRV was reduced
After 30 min - SCS no effect on baseline myocardial electrophysiology or hemodynamics

11. Effect of SCS During Acute Ischemia
SCS attenuated sympathetic excitation associated ARI reduction in ischemic myocardium *
Activation recovery interval (ARI) = RT - AT
Acute ischemia is associated with reflex sympathoexcitation causing ARI shortening and increase in dispersion in control states. What we found with SCS is that SCS attenuated….

12. Effect of SCS During Acute Ischemia* *
During ischemia - SCS was associated with a greater: Increase in Activation time (AT) and Reduction in Repolarization time (RT)

13. Effect of SCS During Acute Ischemia* *
SCS attenuated sympathetic excitation associated increase in dispersion in ischemic myocardium

14. Effect of SCS During Acute Ischemia
NSVT during Ischemia
Sham – 24/3 of 10 animals
SCS – 1/1 of 10 animals
PVC’s during Ischemia
Sham – 19 (0-105)
SCS – 7 (0-17)
SCS attenuated decrement in LV function with ischemia and may reduce ventricular arrhythmias

15. Effect of SCS During Reperfusion
SCS was associated with
Reduction in Tp-Te prolongation during reperfusion
Improvement in LV function during ischemia and reperfusion

16. Conclusions
SCS attenuates cardiac sympathoexcitation and stabilizes cardiac electrophysiology during myocardial ischemia
SCS increased myocardial electrical wave stability
There was no effect of SCS on cardiac electrophysiology during basal conditions, only during times of myocardial afferent sympathetic hyperactivity
With acute ischemia and an increase in cardiac afferent signaling, SCS modulated the afferent spinal input and stabilized efferent output thus decreasing ventricular arrhythmogenicity
Attenuates sympathoexcitation: attenuation of action potential RT reduction and ARI shortening
Electrical wave stability: reduction in ventricular dispersion of repolarization and ARI.
and providing important mechanistic insight into SCS anti-ÿarrhythmic effects.

17. Acknowledgements
UCLA Neurocardiology Research Team Tatsuo Takamiya MD Yukiko Kubo MD Erica A. Dale PhD Wei Zhou PhD Jasmine Kipke BS Aman Mahajan MD PhD SCA and FAER foundations for funding support
Add lab people, department, and FAER