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October 13, 2014
8:00 AM - 10:00 AM
Room Room 265-268
Cardiospinal Reflex Modulation of Ventricular Arrhythmogenesis
Kimberly J. Howard-Quijano, M.D., Kent Yamakawa, M.D., Wei Zhou, Ph.D., Kalyanam Shivkumar, M.D., Ph.D., Aman Mahajan, M.D., Ph.D.
University of California at Los Angeles, Los Angeles, California, United States

Sudden cardiac death (SCD) due to ventricular tachyarrhythmias is the leading cause of mortality in the USA, causing 400,000 deaths/year. The autonomic nervous system is now recognized as a large contributor to the pathophysiology of lethal arrhythmias. Selective neuraxial modulation, such as thoracic epidural anesthesia and stellate ganglion blocks, provide novel therapeutic pathways to SCD intervention. However, there are major gaps in understanding neuraxial regulation of cardiac excitability- from the spinal ganglia and spinal cord to the intrinsic cardiac nervous system. The goal of this study is to determine the role of cardiac afferent neural inputs, from the heart to the spinal cord, in modulating sympathetic control of ventricular electrophysiology in normal hearts. We hypothesized that the dorsal root afferent neural input tonically modulates efferent sympathetic control of the heart.


Yorkshire pigs (n=11) underwent surgical exposure of the heart and left and right stellate ganglion (LSG and RSG) through thoracotomy. Dorsal and ventral roots of the spinal cord at T1-4 were exposed through laminectomy. A 56-electrode sock was placed over the ventricles to record epicardial electrograms. Animals underwent LSG and RSG stimulation (LSGS, RSGS) for 30 seconds before spinal cord roots transection (Rhizotomy), and after the following procedures at T1-T4: (1) left dorsal roots transection (Lt. DRTx); (2) left ventral roots transection (Lt. DVTx); and (3) right dorsal and ventral roots transection (Bil. DVRTx) Activation recovery intervals (ARIs), as surrogate for action potential duration, and regional dispersion of repolarization were measured before and during stimulation. Increased sympathetic excitability is associated with shortening of ARIs and increased dispersion.


LSGS and RSGS with intact spinal roots significantly shortened the global ARI from baseline (LSGS) 367±39 to 349±52 ms, (RSGS) 360±34 to 291±55 ms and increased the dispersion of repolarization from (LSGS) 421±139 to 1008±284 ms2, (RSGS) 369±102 to 693±207 ms2. Left dorsal root transection resulted in significant shortening of the global mean ARI, in the setting of no stimulation (baseline) 312±35 to 284±53 (Figure 1). LSGS and RSGS following left dorsal root transection further shortened the ARI by 18.9% and 15.4% (p<0.05), respectively without altering the ARI dispersion. LSGS and RSGS following left ventral root transection and bilateral dorsal and ventral root transection have significant shorter ARIs than that with intact, but with no significant difference compared to the left dorsal root transection.


Interruption of spinal afferent signals at T1-T4 results in enhanced cardiac sympathoexcitability. This suggests that afferent neuronal signals, from the heart to the spinal cord, exert inhibitory control of myocardial excitability. Dorsal rhizotomy creates increased sympathetic discharge that will be mitigated by ventral nerve root transection. This finding provides mechanistic insight into the role of thoracic spinal integration of cardiac afferent signals in regulation of cardiac excitability, and provides novel targets for neuromodulation therapy.
Figure 1

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