Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.661589
Title: Dietary fat and ischaemic arrhythmias
Author: Sargent, Carol A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1990
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Abstract:
Sudden cardiac death constitutes over a quarter of the total mortality from coronary heart disease in man. The cause of these deaths is assumed to be the cardiac rhythm disturbance, ventricular fibrillation (VF). Any intervention which might reduce VF is of major clinical importance. Diets enriched with unphysiologically large quantities of the polyunsaturated fatty acid (PUFA), 18:2(n-6) have been shown to reduce ventricular fibrillation in animals. However such diets also result in reciprocal changes in other nutrients. The primary aim of this thesis was to confirm the antiarrhythmic effect of 18:2(n-6) on ischaemic arrhythmias using balanced semi-synthetic diets and to determine its mechanism. Arrhythmias were studied during coronary artery ligation (20 minutes) in the isolated rat heart, Langendorff perfused with a modified Krebs-Henseleit buffer (K+ = 3.0mM). The influence of these diets on myocardial phospholipid fatty acid composition was also examined. Ichaemic VF was studied in inbred rats fed a standardised semi-synthetic control diet (PUFA/saturated fatty acid ratio (P/S) 0.3) to identify an arrhythmia prone strain. The results suggested a genetic influence on the incidence of VF which was associated with altered fat metabolism. Dietary recommendations aimed at reducing heart disease include a decrease in total fat intake to 30% energy. The effect of different total fat diets (20,30,40% energy) with high or low PUFA (n-6) levels on the incidence of ischaemic VF was studied. As reported previously an antiarrhythmic effect was observed with the high fat, high P/S ratio diet. This effect was maintained at 30% energy from fat, but at 20% energy this protective effect was attenuated. Myocardial PUFA phospholipid distribution (bar arachidonic acid) was altered with high PUFA diets. Correlations with the incidence of VF were found between dietary saturated (r = 0.825) and polyunsaturated (r = 0.925) fatty acids. An unexpected pattern towards an increased number of fatty acid changes with a reduction in total fat from 40 to 30 to 20% energy was found. Diets are enriched with PUFA's at the detriment of saturated fatty acids. To distinguish between these two factors an experiment was designed to determine the relative importance of dietary saturated fat, PUFA fat and the P/S ratio to ischaemic VF. The dominant factor was found to be the P/S ratio. Indomethacin, a non-steroidal anti-inflammatory drug has been shown to diminish the antiarrhythmic effect of high PUFA diets. The more selective cyclo-oxygenase inhibitor flurbiprofen did not reduce the antiarrhythmic effect of high PUFA diets. The effect of fish oil (rich in PUFA of the n-3 family) on ischaemic arrhythmias was also studied. This was to determine whether the antiarrhythmic effect was a general PUFA property or specific to the n-6 essential PUFA's. The results from feeding realistic amounts of fish oil (0.4% KCal as n-3 fatty acids) showed a trend towards an antiarrythmic effect. In conclusion the most important antiarrhythmic dietary factor is the P/S ratio, associated with PUFA incorporation into myocardial cell membrane phospholipid. This could modulate membrane function without an alteration in prostanoid release, and thereby the propensity for ischaemic arrhythmias.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.661589  DOI: Not available
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