First published October 31, 2019 - More info
Rationale: Reflex-mediated sympathoexcitation is central to the pathogenesis of arrhythmias and heart disease; neuraxial modulation can favorably attenuate these cardiac reflexes leading to cardioprotection. Objective: The purpose of this study was to define the mechanism by which cardiac neural decentralization and spinal cord stimulation (SCS) reduces ischemia-induced ventricular fibrillation (VF) and sudden cardiac death (SCD) by utilizing direct neurotransmitter measurements in the heart. Methods and Results: Direct measurement of norepinephrine (NE) levels in the left ventricular (LV) interstitial fluid (ISF) by microdialysis in response to transient left anterior descending coronary artery occlusion (CAO: 15 min) in anesthetized canines. Responses were studied with: (i) intact neuraxis and were compared to those in which the (ii) intrathoracic component of the cardiac neuraxis (stellate ganglia),(iii) the intrinsic cardiac neuronal (ICN) system were surgically delinked from the central nervous system versus (iv) subjects with intact neuraxis subjected to pre-emptive SCS (T1-T3 spinal level). With an intact neuraxis, animals with exaggerated NE-ISF levels in response to CAO were at increased risk for VF and SCD. During CAO there was a 152% increase in NE level when the entire neuraxis was intact compared to 114% following intrathoracic neuraxial decentralization (removal of the stellates) and 16% increase following ICN decentralization, when the entire heart and ICN was delinked from the other levels of the neuraxis. During SCS, CAO increased NE levels by 59%. Risk for CAO-induced VF was 38% in controls, 8% following total decentralization and 11% following SCS. Conclusions: These data indicate that ischemia related afferent neuronal transmission engages central and intrathoracic sympathetic reflexes which amplifies sympathoexcitation and results in an increase in regional ventricular NE release that causes VF and SCD. Surgical decentralization or SCS prevents this amplification of sympathoexcitation, attenuating the resultant NE release, and reduces VF and SCD.