Dual Neuromodulation Strategy for Post-ischemic Arrhythmia Suppression: Spinal Cord and Vagus Nerve Stimulation

Introduction: Ischemia-induced ventricular arrhythmias remain a leading cause of sudden cardiac death, yet current preventive strategies fail to adapt to the rapidly changing autonomic disturbances that underlie arrhythmogenesis. Single-modality neuromodulation approaches, such as spinal cord stimulation (SCS) or vagus nerve stimulation (VNS), have shown promise but yield inconsistent results, partly due to non-reciprocal and sometimes simultaneous activation of sympathetic (SNS) and parasympathetic (PSNS) pathways in diseased hearts. This “autonomic conflict” can limit efficacy and even exacerbate arrhythmia risk.

Dual-site neuromodulation offers a mechanistically superior alternative by directly and simultaneously modulating SNS (via SCS) and PSNS (via VNS) activity to restore autonomic balance. Guided by heart rate variability (HRV) as a real-time biomarker of autonomic tone, we developed a closed-loop SCS+VNS system to dynamically counter ischemia-induced sympathoexcitation and arrhythmogenic substrate formation. This study evaluated the safety and anti-arrhythmic efficacy of HRV-guided dual neuromodulation in a porcine model of acute myocardial ischemia.

Methods: A closed-loop SCS+VNS system guided by HRV was evaluated in six anesthetized pigs undergoing LAD occlusion to induce acute myocardial ischemia. Epidural leads at T1–T4 delivered SCS and a cervical cuff electrode delivered VNS, with stimulation dynamically adjusted to maintain autonomic balance. Epicardial electrograms were used to measure ARI as a surrogate for action potential duration and DOR as an index of arrhythmogenic substrate. Arrhythmia incidence, defined as the occurrence of sustained ventricular tachycardia during ischemia, was recorded and compared with historical ischemia-only controls (n=16). Statistical analysis included t-tests for ARI and DOR changes and Chi-square tests for arrhythmia incidence.

Results: Closed-loop SCS+VNS significantly mitigated ischemia-induced ARI shortening (p < 0.001) and suppressed the ischemia-related increase in DOR (p < 0.001) compared with ischemia-only controls. Sustained ventricular tachycardia occurred in 0/6 treated animals versus 14/16 in controls (p < 0.001). No episodes of bradycardia, hypotension, or ventricular dysfunction were observed during stimulation.

Conclusion: HRV-guided closed-loop SCS+VNS safely and effectively reduced ischemia-induced electrophysiological instability and prevented sustained ventricular tachycardia in a porcine model. These findings provide strong preclinical support for dual-site, real-time autonomic neuromodulation as a novel strategy to suppress malignant arrhythmias and protect the ischemic heart.