Thoracic spinal cord neuromodulation obtunds dorsal root ganglion afferent neuronal transduction of the ischemic ventricle

Abstract

Aberrant afferent signaling drives adverse remodeling of the cardiac nervous system in ischemic heart disease. The study objective was to determine whether thoracic spinal dorsal column stimulation (SCS) modulates cardiac afferent sensory transduction of the ischemic ventricle. In anesthetized canines ( n = 16), extracellular activity generated by 62 dorsal root ganglia (DRG) soma (T1-T3), with verified myocardial ischemic (MI) sensitivity, were evaluated with and without 20-min preemptive SCS (T1-T3 spinal level; 50 Hz, 90% motor threshold). Transient MI was induced by 1-min coronary artery occlusion (CAO) of the left anterior descending (LAD) or circumflex (LCX) artery, randomized as to sequence. LAD and LCX CAO activated cardiac-related DRG neurons (LAD: 0.15 ± 0.04–1.05 ± 0.20 Hz, P < 0.00002; LCX: 0.08 ± 0.02–1.90 ± 0.45 Hz, P < 0.0003). SCS decreased basal neuronal activity of neurons that responded to LAD (0.15 ± 0.04 to 0.02 ± 0.01 Hz, P < 0.006) and LCX (0.08 ± 0.02 to 0.02 ± 0.01 Hz, P < 0.003). SCS suppressed responsiveness to transient MI (LAD: 1.05 ± 0.20–0.03 ± 0.01 Hz; P < 0.0001; LCX: 1.90 ± 0.45–0.03 ± 0.01 Hz; P < 0.001). Suprathreshold SCS (1 Hz) did not activate DRG neurons antidromically ( n = 10 animals). Ventricular fibrillation (VF) was associated with a rapid increase in DRG activity to a maximum of 4.39 ± 1.07 Hz at 20 s after VF induction and a return to 90% of baseline within 10 s thereafter. SCS obtunds the capacity of DRG ventricular neurites to transduce the ischemic myocardium to second-order spinal neurons, a mechanism that would blunt reflex sympathoexcitation to myocardial ischemic stress, thereby contributing to its capacity to cardioprotect. NEW & NOTEWORTHY Aberrant afferent signaling drives adverse remodeling of the cardiac nervous system in ischemic heart disease. This study determined that thoracic spinal column stimulation (SCS) obtunds the capacity of dorsal root ganglia ventricular afferent neurons to transduce the ischemic myocardium to second-order spinal neurons, a mechanism that would blunt reflex sympathoexcitation to myocardial ischemic stress. This modulation does not reflect antidromic actions of SCS but likely reflects efferent-mediated changes at the myocyte-sensory neurite interface. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/spinal-cord-stimulation-blunts-dorsal-root-transduction-of-the-ischemic-ventricle/ .

Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

“…In this study, DRGS prevented the reduction in ARI seen as a result of sympathetic hyperactivity during induced cardiac stress with programmed ventricular extrastimuli (S1S2 pacing). We and others have previously shown that ARI shortening occurs during increases in sympathetic discharge following cardiac stress (Vaseghi et al, 2013;Howard-Quijano et al, 2017a,b;Omura et al, 2021), and neuromodulation can block the cardiospinal neural reflex and prevent exaggerated sympathetic output to the heart (Salavatian et al, 2019). Our results show that DRGS reduced the cardiac sympathetic output via controlling the afferent arm of the cardio-neural reflex.…”

Optical Activation of the Dorsal Horn of the Thoracic Spinal Cord Prevents Ventricular Arrhythmias in Acute Myocardial Ischemia-Reperfusion Rats

“…Previous studies have shown that SCS significantly ameliorates myocardial ischemia and ventricular arrhythmias during ischemia and reperfusion (4,22). SCS significantly inhibits the abnormal activity of neurons in the dorsal horn at the T1-4 level (5). In this study, we confirmed that the pre-activation of glutamatergic neurons in the T1 dorsal horn inhibited ventricular arrhythmias during ischemia-reperfusion, suggesting that glutamatergic neurons played an important role in the protective mechanisms of SCS.…”

“…Previous studies have reported that epidural anesthesia or spinal cord stimulation (SCS) reduces sympathetic excitation and malignant ventricular arrhythmias (4). SCS modulates afferent nervous signals (5), sympathetic neurotransmitter release (6,7), and autonomic dysregulation (4). Multiple interactions among neurons in the thoracic spinal cord may be involved in cardiac sympathetic overactivation (8).…”

Autonomic modulation of ventricular electrical activity: recent developments and clinical implications

“…As with many other neuromodulatory therapies, spinal cord stimulation (SCS) was initially developed to treat angina pectoris [143,144]. Though not completely understood, local stimulation of the spinal cord affects various central and local neural circuits, which collectively impede the process of arrhythmogenesis [145][146][147][148][149][150][151][152][153]. For instance, SCS impedes the ability of afferent cardiac nerves in transferring their signal to second-order spinal cord neurons, thereby hampering the initiation of a sympathetic reflex and the development of sympathetically driven remodeling processes that are induced by myocardial ischemia [146,147].…”

“…Though not completely understood, local stimulation of the spinal cord affects various central and local neural circuits, which collectively impede the process of arrhythmogenesis [145][146][147][148][149][150][151][152][153]. For instance, SCS impedes the ability of afferent cardiac nerves in transferring their signal to second-order spinal cord neurons, thereby hampering the initiation of a sympathetic reflex and the development of sympathetically driven remodeling processes that are induced by myocardial ischemia [146,147]. In addition, SCS stabilizes the ICNS and decreases left stellate ganglion activity, all of which could contribute to its antiarrhythmic effects [148,149,154].…”