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Title: Electrophysiological effects of substrate manipulation during acute myocardial ischaemia
Author: Russell, Douglas C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1979
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Alterations of substrate availability may modulate the energy balance within ischaemic myocardium. Electrophysiological effects of substrate manipulation have been examined therefore in the open chest anaesthetised dog following acute experimental coronary arterial occlusion over the period of the early phase of enhanced ventricular vulnerability to arrhythmias. Three experimental models are described permitting combined measurements of myocardial metabolic gradients (arterial-local venous differences), regional myocardial blood flow (RMBF), and a) ventricular premature beat thresholds (VPBT) b) regional ventricular refractory periods (RP) and c) epicardial action potential (AP) and endocardial-epicardial conduction (CT) changes both before and during successive short periods of occlusion of the left anterior descending coronary artery. Coronary occlusion resulted in a phase of enhanced ventricular vulnerability to arrhythmias (lowered VPBT) maximal after 5 minutes of ischaemia; varied patterns of change of RP, with RP prolongation dominant in central ischaemic zones and RP shortening in border zones; AP shortening, "slow response" type activity, electrical alternans, and increasing CT. Ventricular fibrillation (VF) was preceded by maximal RP divergence, maximal CT, AP shortening, alternans and intermittent conduction block. Effects were enhanced by increased heart rate and in initial occlusions. Elevation of plasma glucose concentrations during moderate ischaemia (c.50% normal RMBF) increased VPBT between 2 and 7 minutes after occlusion, compared with control mannitol infusion; reduced VPB frequency; reduced RP shortening and RP gradients; reduced AP shortening, CT and ST-segment elevation; and increased arterial-local venous differences of glucose without change in RMBF. During severe ischaemia (high proximal occlusion) there was no effect on VF incidence and transient effects only on AP shortening and CT. Inhibition of isoprenaline stimulated lipolysis during moderate ischaemia resulted in halving of arterial free fatty acid and glycerol concentrations and small reductions in RP gradients, AP shortening, CT and ST-segment elevation, but no change in VPBT. There was no effect on RMBF.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available