John, Mattathu Roy; (1992) The monophasic action potential as an index of myocardial ischaemia: Studies incorporating myocardial perfusion scintigraphy. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Malignant ventricular arrhythmias continue to be the major cause of death in relation to myocardial ischaemia. The basic electrophysiological alterations that accompany the onset of myocardial ischaemia have been extensively studied in in vitro preparations and animal studies. However, studies of myocardial ischaemia in man are limited by the difficulty in recording basic electrophysiological changes in the beating heart. Furthermore, such studies require production of controlled ischaemia and the ability to detect and verify such ischaemia during the electrophysiological study. This thesis has developed this technically complex approach. The advent of the monophasic action potential (MAP) recording technique using pressure contact electrodes has allowed the study of myocardial cellular repolarization characteristics in human hearts during cardiac catheterisation. Also, advances in myocardial perfusion imaging techniques with the development of newer 99m technetium isonitrile analogues have made possible, the use of myocardial perfusion scintigraphy to document myocardial perfusion characteristics during interventions in the cardiac catheterisation laboratory. This thesis is based on a series of studies that have examined the use of MAPs to document typical early electrophysiological changes of myocardial ischaemia during experimental myocardial ischaemia and its use in combination with technetium 99m hexakis-2-methoxy-2-methylpropyl-isonitrile (99mTc- MIBI) myocardial perfusion scintigraphy to study myocardial ischaemia in patients during cardiac catheterisation. An initial study in intact porcine hearts during transient coronary occlusion examined the ability of action potentials recorded by the MAP technique to register early changes of myocardial ischaemia from the ventricular endocardium. A second study in 26 patients undergoing cardiac catheterisation used endocardial recordings of the MAP during atrial pacing to angina threshold. Ischaemic areas of myocardium were identified by injection of 99m Tc-MIBI at peak pacing stress. Recordings from the ischaemic endocardial regions showed a significantly greater shortening of action potential duration corrected for heart rate changes compared with the non-ischaemic areas. Sensitivity and specificity of various changes in MAP duration per unit change in heart rate for the detection of myocardial ischaemic were derived. The third study used endocardial recordings of the MAP as a measure of myocardial ischaemia during dypiridamole myocardial perfusion imaging in patients with coronary artery disease.Finally, the combination of MAP recordings and 99m Tc-MIBI perfusion scintigraphy was employed to study regional and potential arrhythmogenic effects of beta adrenoceptor stimulation in potentially ischaemic versus normal areas of human myocardium. MAPs were recorded simultaneously from the right and left ventricular endocardium in 14 patients (28 recording sites) during infusion of dobutamine. Perfusion at the recording site was assessed by the injection of 99m Tc-MIBI at peak doses of dobutamine. Action potential duration during dobutamine was compared to that during atrial pacing to identical pacing rates in the absence of dobutamine. In 21 recordings from normally perfused recordings, dobutamine produced a variable effect on the action potential duration over and above that produced by atrial pacing alone to identical pacing rates either lengthening or shortening the action potential duration. In the ischaemic zones, dobutamine invariably shortened the action potential duration. The data provide a possible mechanistic basis for the beneficial effects of beta adrenergic blockade in ischaemic heart disease. A unique series of studies combining basic electrophysiological studies with a radionuclide imaging technique is presented. Validation and application of the two techniques to evaluate regional myocardial ischaemia and arrhythmogenic potential in the human heart are addressed.

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