Experimental studies on myocardial blood flow and metabolism with special reference to hyperbaric oxygen

McBride, Thomas I (1969) Experimental studies on myocardial blood flow and metabolism with special reference to hyperbaric oxygen. MD thesis, University of Glasgow.

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In the last few years there has been a renewal of interest in the use of hyperbaric oxygen as a therapeutic measure. Much work has been published on its use in various clinical situations and efforts have been made to use this mechanism in the treatment of different types of heart disease. It has become increasingly clear however that an understanding of the fundamental changes in myocardial blood flow and metabolism which occur on exposure to high partial pressures of oxygen was lacking. Furthermore, little well documented experimental work was available. It was decided therefore to plan an investigation into the effects of oxygen at high pressure on myocardial blood flow and metabolism. The experimental animal was the dog and the main locus of the work was the Hyperbaric Unit at the Western Infirmary, Glasgow. A brief review is given of the history of investigation of myocardial blood flow and a short summary of the types of methods available for such an investigation. The technique selected for measuring myocardial blood flow utilised the clearance of the radio-active 133Xenon from the myocardium. The theoretical basis of this method is then described and the practical details outlined. The establishment of the method in the laboratory follows. The first experimental work concerned the effect of high partial pressures of oxygen on myocardial blood flow. These experiments were conducted at a pressure of 2 atmospheres absolute. It was shown that an abrupt change of arterial oxygen tension from 100 mm.Hg. (defined as "air equivalent") to 1000 mm.Hg. was associated with a 25% reduction in myocardial blood flow. Although it was thought unlikely that this reduction in flow would be mediated through nervous pathways a series of experiments was devised to investigate this possibility. The change in flow was studied after (a) injections of atropine and propranolol (a beta adrenergic blocking drug), (b) injections of phenoxybenzamine (an alpha blocking drug) and (c) bretylium tosylate (an adrenergic neurone blocking drug). As the reduction in flow or changing from air equivalent to oxygen was maintained after these injections it was concluded that this reduction in flow is not reflexly caused. A direct effect of oxygen on vascular smooth muscle was thought to be responsible. Myocardial oxygen consumption and metabolism were studied during this change from air equivalent to oxygen breathing. The metabolic parameters studied were the extraction of lactate, pyruvate and glucose. Oxygen consumption, lactate consumption and pyruvate consumption were all substantially reduced, No change was noted in the consumption of glucose. The next experimental work concerned the effect of high partial pressures of carbon dioxide on myocardial blood flow and oxygen consumption. This work was performed at normal atmospheric pressure. Raised arterial carton dioxide tension was associated with a rise in myocardial blood flow and a fall in oxygen consumption. Because of these results the effect of high arterial tensions of carbon dioxide combined with hyperbaric oxygen was studied. A further fall in oxygen and substrate metabolism occurred but a substantial increase in myocardial blood flow was noted. It is suggested that carbon dioxide may have a direct vasodilator effect on myocardial vasculature and an indirect effect which may impair cellular metabolism. The final group of experiments concerned the changes which occurred in myocardial flow and metabolism when the change from air equivalent to oxygen was prolonged for 5 hours. The myocardial blood flow fell substantially, oxygen consumption was further reduced and evidence of marked interference with carbohydrate metabolism was found. In addition the expected fall in cardiac output was confirmed and evidence was found of interference with atrio-ventricular conduction in the heart in three cases. These changes all tended to return to normal when administration of air equivalent was resumed. The likelihood of a toxic effect of high partial pressures of oxygen on the myocardium is discussed. Finally a general summary of the results is presented and the clinical and laboratory implications of these studies reviewed.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Iain McA Ledwingham
Keywords: Medicine, Physiology
Date of Award: 1969
Depositing User: Enlighten Team
Unique ID: glathesis:1969-73706
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56
URI: https://theses.gla.ac.uk/id/eprint/73706

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