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Title: Role of the vagus nerve and intrinsic cardiac ganglia in both remote and local myocardial ischaemic conditioning
Author: Pickard, J. M. J.
ISNI:       0000 0004 7225 0375
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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BACKGROUND: There is a clear clinical need for interventions that limit the extent of injury associated with myocardial ischaemia-reperfusion injury (IRI). Two such interventions are classical (IPC) and remote (RIC) ischaemic preconditioning. The mechanism of action in both cases involves release of one or more humoral factors. However, the existence of a neural pathway remains equivocal. The aim of this thesis was to investigate the importance of a neural pathway in both classical and remote ischaemic conditioning, with particular focus on the vagus nerve and intrinsic cardiac ganglia. In addition, the efficacy of noninvasive vagus nerve stimulation was investigated as a novel cardioprotective intervention. Finally, we performed a meta-analysis investigating the efficacy of RIC in animal in vivo models of myocardial infarction. Methods and Results This thesis first aimed to investigate the co-dependence between the neural and humoral pathways of RIC. Bilateral cervical vagotomy abolished release of the humoral blood-borne mediator. Moreover, pharmacological antagonism of intrinsic cardiac ganglia abrogated RIC-mediated protection. This thesis was the first to reveal a neural component to the mechanism of IPC. We suggest a sensory feedback loop in response to IPC, involving activation intrinsic cardiac ganglia and post-ganglionic parasympathetic fibres projecting to the ventricles. Finally, transcutaneous vagus nerve stimulation (tVNS) in healthy human volunteers induced release of a blood-borne cardioprotective factor. However, tVNS was not significantly cardioprotective in an in vivo rat model of IRI. Conclusions Release of the humoral blood-borne mediator following RIC is dependent on prior vagus nerve activation. Furthermore, intrinsic cardiac ganglia are recruited as part of the mechanism of both RIC and IPC. Finally, tVNS is suggested to be a novel cardioprotective intervention.
Supervisor: Yellon, D. M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available