Long-term spinal cord stimulation modifies canine intrinsic cardiac neuronal properties and ganglionic transmission during high-frequency repetitive activation.

Frank M Smith,Michel Vermeulen,René Cardinal

doi:10.14814/phy2.12855

Frank M Smith, Michel Vermeulen + Show 1 more

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https://doi.org/10.14814/phy2.12855

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Abstract

Long‐term spinal cord stimulation (SCS) applied to cranial thoracic SC segments exerts antiarrhythmic and cardioprotective actions in the canine heart in situ. We hypothesized that remodeling of intrinsic cardiac neuronal and synaptic properties occur in canines subjected to long‐term SCS, specifically that synaptic efficacy may be preferentially facilitated at high presynaptic nerve stimulation frequencies. Animals subjected to continuous SCS for 5–8 weeks (long‐term SCS: n = 17) or for 1 h (acute SCS: n = 4) were compared with corresponding control animals (long‐term: n = 15, acute: n = 4). At termination, animals were anesthetized, the heart was excised and neurones from the right atrial ganglionated plexus were identified and studied in vitro using standard intracellular microelectrode technique. Main findings were as follows: (1) a significant reduction in whole cell membrane input resistance and acceleration of the course of AHP decay identified among phasic neurones from long‐term SCS compared with controls, (2) significantly more robust synaptic transmission to rundown in long‐term SCS during high‐frequency (10–40 Hz) presynaptic nerve stimulation while recording from either phasic or accommodating postsynaptic neurones; this was associated with significantly greater posttrain excitatory postsynaptic potential (EPSP) numbers in long‐term SCS than control, and (3) synaptic efficacy was significantly decreased by atropine in both groups. Such changes did not occur in acute SCS. In conclusion, modification of intrinsic cardiac neuronal properties and facilitation of synaptic transmission at high stimulation frequency in long‐term SCS could improve physiologically modulated vagal inputs to the heart.

Highlights

Spinal cord stimulation (SCS) applied to upper thoracic SC segments is a neuromodulatory approach used for the treatment of refractory angina pectoris (Eliasson et al 1996; Ekre et al 2002)
Using excised right atrial ganlionated plexus (RAGP) preparations, we investigated the propositions that (1) synaptic efficacy was preferentially facilitated in long-term SCS at high presynaptic stimulation frequency, and (2) intrinsic neuronal membrane and action potential properties as well as muscarinic synaptic mechanisms were modified by long term-SCS
There were no differences between groups in resting membrane potential (RMP), voltage displacement to threshold potential (DVt) or action potential amplitude (AP ampl)

Summary

Introduction

Spinal cord stimulation (SCS) applied to upper thoracic SC segments is a neuromodulatory approach used for the treatment of refractory angina pectoris (Eliasson et al 1996; Ekre et al 2002). In the long-term SCS study, we reported preliminary data suggesting that the synaptic properties of cardiac autonomic ganglia studied in vitro were modified (Ardell et al 2014). This is an important observation to pursue as neurotransmission in canine cardiac ganglia is attenuated in experimental heart failure (Bibevski and Dunlap 1999) and may contribute to the impaired vagal control seen in clinical heart failure (Bibevski and Dunlap 2011). The RAGP is an epicardiac ganglionated plexus nested in a large fat pad that is readily identified at the right pulmonary vein-right atrial junction, receiving vagal inputs via mediastinal nerves entering the epicardium and providing postganglionic innervation to the right atrial wall and sinus node region (Randall et al.1987; Pauza et al 1999; Cardinal et al 2009)

Ethical approval and animals

Terminal procedure and in vitro preparation

Results

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Discussion