Integrative Cardiovascular Physiology and Pathophysiology: Spinal cord stimulation reduces ventricular arrhythmias during acute ischemia by attenuation of regional myocardial excitability

摘要

Myocardial ischemia creates autonomic nervous system imbalance and can trigger cardiac arrhythmias. We hypothesized that neuromodulation by spinal cord stimulation (SCS) will attenuate local cardiac sympathoexcitation from ischemia-induced increases in afferent signaling, reduce ventricular arrhythmias, and improve myocardial function during acute ischemia. Yorkshire pigs (n = 20) were randomized to SCS (50 Hz at 200-μs duration, current 90% motor threshold) or sham operation (sham) for 30 min before ischemia. A four-pole SCS lead was placed percutaneously in the epidural space (T1–T4), and a 56-electrode mesh was placed over the heart for high-resolution electrophysiological recordings, including activation recovery intervals (ARIs), activation time, repolarization time, and dispersion of repolarization. Electrophysiological and hemodynamic measures were recorded at baseline, after SCS/sham, during acute ischemia (300-s coronary artery ligation), and throughout reperfusion. SCS 1) reduced sympathoexcitation-induced ARI and repolarization time shortening in the ischemic myocardium; 2) attenuated increases in the dispersion of repolarization; 3) reduced ventricular tachyarrythmias [nonsustained ventricular tachycardias: 24 events (3 sham animals) vs. 1 event (1 SCS animal), P < 0.001]; and 4) improved myocardial function (dP/dt from baseline to ischemia: 1,814 ± 213 to 1,596 ± 282 mmHg/s in sham vs. 1,422 ± 299 to 1,380 ± 299 mmHg/s in SCS, P < 0.01). There was no change in ventricular electrophysiology during baseline conditions without myocardial stress or in the nonischemic myocardium. In conclusion, in a porcine model of acute ventricular ischemia, SCS reduced regional myocardial sympathoexcitation, decreased ventricular arrhythmias, and improved myocardial function. SCS decreased sympathetic nerve activation locally in the ischemic myocardium with no effect observed in the normal myocardium, thus providing mechanistic insights into the antiarrhythmic and myocardial protective effects of SCS.>NEW & NOTEWORTHY In a porcine model of ventricular ischemia, spinal cord stimulation decreased sympathetic nerve activation regionally in ischemic myocardium with no effect on normal myocardium, demonstrating that the antiarrhythmic effects of spinal cord stimulation are likely due to attenuation of local sympathoexcitation in the ischemic myocardium and not changes in global myocardial electrophysiology.