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Metabolic support in left ventricular hypertrophy

Howell, Neil John (2011)
Ph.D. thesis, University of Birmingham.

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Aims: To examine the metabolic changes associated with LVH secondary to AS, to examine the role of GIK as an adjunct to myocardial protection during AVR, and to examine the mechanism of its action. Methods: 220 patients with LVH secondary to AS were randomised 1:1 to receive an infusion of GIK at the time of AVR. The primary endpoint of the trial was incidence of low cardiac output state. At pre-specified time points, biopsies of the LV anterior wall were taken for analysis of metabolic changes associated with LVH, and changes in the phosphorylation state of proteins identified as key regulators of metabolism and cardiac protection. Results: Patients with LVH were found to exhibit a profound down-regulation of the mRNA transcript levels of the master transcriptional regulators of metabolism resulting in a significantly abnormal metabolome. Treatment with GIK was associated with a reduction in LCOS from 33% in the control group to 10% in the treatment group, p=0.0001. Treatment with GIK was associated with a significant increase in the level of protein O-GlcNAcylation. Conclusions: In this trial, treatment with GIK was associated with a significant improvement in post-operative haemodynamics. Patients with LVH may benefit from metabolic therapies at the time of surgery

Type of Work:Ph.D. thesis.
Supervisor(s):Pagano, Domenico
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Experimental and Clinical Medicine
Subjects:RC Internal medicine
Institution:University of Birmingham
ID Code:1492
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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