Spinal Cord Stimulation Reduces Ventricular Arrhythmias by Attenuating Reactive Gliosis and Activation of Spinal Interneurons.

OBJECTIVES

This study investigated spinal cord neuronal and glial cell activation during cardiac ischemia-reperfusion (IR)-triggered ventricular arrhythmias and neuromodulation therapy by spinal cord stimulation (SCS).

BACKGROUND

Myocardial ischemia induces changes in cardiospinal neural networks leading to sudden cardiac death. Neuromodulation with SCS decreases cardiac sympathoexcitation; however, the molecular mechanisms remain unknown.

METHODS

Yorkshire pigs (n = 16) were randomized to Control, IR, or IR+SCS groups. A 4-pole SCS lead was placed in the T1-T4 epidural space with stimulation for 30 minutes before IR (50 Hz, 0.4-ms duration, 90% motor threshold). Cardiac electrophysiological mapping and Ventricular Arrhythmia Score (VAS) were recorded. Immunohistochemistry of thoracic spinal sections was used to map and identify Fos-positive neuronal and glial cell types during IR with and without SCS.

RESULTS

IR increased cardiac sympathoexcitation and arrhythmias (VAS = 6.2 ± 0.9) that were attenuated in IR + SCS (VAS = 2.8 ± 0.5; P = 0.017). IR increased spinal cellular Fos expression (#Fos+ cells Control = 23 ± 2 vs IR = 88 ± 5; P < 0.0001) in T1-T4, with the greatest increase localized to T3, and the greatest %Fos+ cells being microglia and astrocytes. Fos expression was attenuated by IR + SCS (62 ± 4; P < 0.01), primarily though a reduction in Fos+ microglia and astrocytes, as SCS also led to increase in Fos+ neurons in deep dorsal laminae.

CONCLUSIONS

In a porcine model, cardiac IR was associated with astrocyte and microglial cell activation. Our results suggest that preemptive thoracic SCS decreased IR-induced cardiac sympathoexcitation and ventricular arrhythmias through attenuation of reactive gliosis and activation of inhibitory interneurons in the dorsal horn of spinal cord.