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Title: On perhexiline and its application to myocardial protection during cardiac surgery
Author: Drury, Nigel Edward
ISNI:       0000 0004 2720 1726
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2012
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Perhexiline is an anti-anginal drug that is thought to shift myocardial metabolism from \(\beta\)-oxidation of fatty acids to glucose utilisation. An associated improvement in energy efficiency may be beneficial in ischaemia-reperfusion as an adjunct to established techniques for myocardial protection during cardiac surgery. In this thesis, I conduct a prospective double-blind randomised placebo-controlled trial of oral perhexiline in patients undergoing coronary artery surgery, obtaining samples of serum, right atrium and left ventricle. I measure the concentration of perhexiline using high performance liquid chromatography and find that although highly concentrated in the heart, it may not have reached steady-state in the ventricular myocardium. I perform enzymatic colourimetry and ultra-high resolution mass spectrometry to detect changes in carbohydrate and lipid metabolism; however, the myocardial metabolic profiles of patients on perhexiline are indistinguishable from controls. On analysing the results of the clinical trial, I find no improvement in the primary endpoint, the incidence of a low cardiac output episode, or any secondary outcomes. I conclude that preoperative oral perhexiline does not improve clinical markers of myocardial protection and despite significant accumulation in the myocardium, it has no significant effect on the measurable metabolic profile of the heart at the time of surgery.
Supervisor: Not available Sponsor: British Heart Foundation ; Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology ; QM Human anatomy ; QP Physiology ; R Medicine (General) ; RZ Other systems of medicine