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Title: Effects of vagus nerve stimulation on ventricular electrophysiology and nitric oxide release
Author: Pongpaopattanakul, Pott
ISNI:       0000 0004 7428 4085
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2018
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Autonomic imbalance is a known hallmark of heart failure (HF). Patients are prone to a sudden cardiac death (SCD) as a result of lethal arrhythmias. Our group has previously shown that vagus nerve stimulation (VNS) protects the heart against ventricular fibrillation (VF) via a nitric oxide (NO) pathway which could be relevant in HF. Clinical studies using vagus nerve stimulators in HF have produced ambiguous outcomes and it has been questioned whether an adequate level of stimulation was actually achieved which raises the question as to the optimal stimulation parameters needed to produce relevant functional effects. In this thesis, the effects of different parameters of VNS on cardiac electrophysiology and NO release were assessed. Hearts from adult male New Zealand White rabbits were procured for dual-innervated Langendorff perfused preparations ex vivo. The cervical vagus was unilaterally stimulated with different voltages, frequencies, and pulse widths. Heart rate (HR), ventricular electrophysiology parameters and NO release in the left ventricle were measured. Results demonstrated an anti-arrhythmic benefit of VNS in all stimulations with involvement of NO release during VNS that protects the heart through the action potential duration restitution mechanism. Data also suggested that NO was released from the neural components within the intra-cardiac nervous system. For VNS parameters, the high amplitude voltage affected the level of HR reduction more but not the level of NO release. In contrast, high frequency VNS, even at very low voltages, alters NO release whilst causing relatively little changes in HR. This current finding confirmed the HR independent protection of VNS and also suggested an importance of stimulation frequency to cause NO release in this action. Low strength voltage with high frequency VNS was suggested as an optimal setting to be translated to the clinical use to prevent SCD in HF patients.
Supervisor: Ng, G. André ; Rainbow, Rich Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available