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Title: The role of myocardial glycogen in the ischaemic heart
Author: Chao, Feng Zhi
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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More than half of the total mortality from coronary heart disease results from sudden cardiac death, primarily from ventricular fibrillation (VF). The metabolic changes due to ischaemia are believed to play an important role in the genesis of the arrhythmia. Two of the main mechanisms of myocyte cell death in severe ischaemia are inadequate supply of glycolytically produced adenosine triphosphate (ATP) and increased circulating catecholamines (Opie, 1993). Glucose-insulin-potassium (GIK) protects ischaemic myocardium. However, the role of glycolytic ATP is questioned by the results that preconditioned animals have a better recovery although myocardial glycogen was decreased. The precise effect of GIK is still poorly understood. There has been no evidence for the effects of myocardial glycogen on ischaemic noradrenaline (NA) release. Such a study could provide an alternative explanation for the protective effect of myocardial glycogen on VF. Attention was focused on the effects of myocardial glycogen raised by fasting or GIK infusion on the ischaemic myocardium. Isolated perfused rat hearts were used and retrogradely perfused. Myocardial metabolites and coronary lactate production were measured. The effects of insulin on total anoxia induced NA release were examined. Regional myocardial glycogen levels in the non-ischaemic and ischaemic myocardium of fibrillating and non-fibrillating hearts were also studied. Hearts were freeze clamped at the onset on VF for the measurement of myocardial metabolites. Anaesthetics were necessary to do these studies. However, the effects of anaesthetics on myocardial glycogen levels are unknown and were examined. Enhanced myocardial glycogen levels obtained by the use of a perfusate containing high glucose (15 mM) and/or insulin and fasting did not reduce the incidence of ischaemia-induced VF. Pre-perfusion of hearts under normoxic conditions with insulin decreased anoxic NA overflow under conditions of low K+ (3 mM) concentrations. The myocardial glycogen in situ did not increase after 24 hours fasting, but after 48 hours fasting it did increase. However, this did not affect the incidence of ischaemia-induced VF in vitro. The myocardial glycogen levels raised by fasting were normalised within 10 minutes of isolated perfusion with 5.5 mM glucose. Pentobarbitone, which gave the highest myocardial glycogen levels, can be used for glycogen studies in vitro, provided that hypoxia is prevented during the induction of the anaesthesia. In conclusion: The results in this thesis suggest that the method used to increase myocardial glycogen concentration is more important than the glycogen level itself in protecting the heart against ischaemia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available