Spinal cord stimulation mitigates the myocardial ischemia induced sympathoexcitation by suppressing the spinal neural synchrony and intermediolateral nucleus hyperactivity

Myocardial ischemia disrupts the cardiospinal neural network which leads to cardiac sudden death. Spinal cord stimulation (SCS) suppresses the sympathoexcitation caused by myocardial ischemia. However, how SCS modulates the spinal neural network is not known.We hypothesize that SCS decreases myocardial ischemia-induced sympathoexcitation by suppressing the spinal neural synchrony and intermediolateral nucleus (IML) activity.Eight Yorkshire pigs (50-55 kg) with chronic left circumflex coronary artery myocardial infarction (MI) were anesthetized and underwent laminectomy and a sternotomy, 5 weeks post MI. Extracellular in-vivo spinal neural recordings were done by using a 64 channel microelectrode array inserted at the T2 segment of the spinal cord. SCS was performed at 1 kHz, 0.03 ms, 90% motor threshold for 30 mins. Acute (3 min) left anterior descending coronary artery occlusion (LAD CAO) was performed pre- and 1 min post-SCS to evaluate the impact of SCS on spinal neural network processing during myocardial ischemia. Dorsal horn (DH) and IML neural interactions, including normalized neuronal synchrony, activation recovery interval (ARI), and dispersion of repolarization (DOR) (markers of cardiac arrhythmogenesis) were evaluated during myocardial ischemia pre- vs. post- SCS.Firing rate of 1283 recorded spinal neurons increased during 3 mins LAD CAO and 1 min reperfusion pre-SCS (baseline(BL): 0.516 ± 0.038 Hz; LAD CAO: 0.559 ± 0.038 Hz ,P<0.001 vs. BL; reperfusion: 0.524 ± 0.037 Hz ,P<0.001 vs. BL). SCS at 1kHz, mitigated the spinal neural network response to the LAD CAO (BL: 0.509 ± 0.039 Hz; LAD CAO: 0.486 ± 0.036 Hz; reperfusion: 0.489 ± 0.038 Hz, P<0.001 vs. BL). This suppression of neural firing by SCS was observed in both IML (pre-SCS: BL: 0.208 ± 0.033 Hz; LAD CAO: 0.308 ± 0.042Hz ,P<0.001 vs. BL; reperfusion: 0.374 ± 0.048 Hz ,P<0.001 vs. BL; post-SCS: BL: 0.069 ± 0.010 Hz; LAD CAO: 0.080 ± 0.011Hz; reperfusion: 0.109 ± 0.018 Hz) and DH neurons (pre-SCS: BL: 0.033 ± 0.003 Hz; LAD CAO: 0.039 ± 0.003 Hz ,P<0.001 vs. BL; reperfusion: 0.041 ± 0.003 Hz ,P<0.001 vs. BL; post-SCS: BL: 0.036 ± 0.003 Hz; LAD CAO: 0.035 ± 0.003 Hz; reperfusion: 0.029 ± 0.002 Hz, P<0.001 vs. BL). ARI shortening due to LAD CAO was mitigated by SCS (pre-SCS: -43.200 ± 5.206 ms; post-SCS: -29.810 ± 6.495 ms, P< 0.05 vs. pre-SCS). SCS decreased the LAD CAO induced augmented DOR (pre-SCS: 2461.00 ± 350.40 ms2 ; post-SCS: 1996.00 ± 302.00 ms2 , P<0.05 vs. pre-SCS) CONCLUSION: Myocardial ischemia induces sympathoexcitation by increasing the IML activity which is caused by activation of DH neurons and increased spinal neural synchrony. SCS mitigates the adverse effect of myocardial ischemia by suppressing the spinal neural synchrony and IML hyperactivity.