Myocardial energy metabolism in patients undergoing cardiac surgery

Haqzad, Yama Shoaib

August 2018

Thesis or dissertation

© 2018 Yama Shoaib Haqzad. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

In chapter 1, short and long term outcomes were assessed in diabetic phenotypes. The phenotypes have been propensity matched for factors that significantly contribute to outcomes. Tablet controlled diabetics have worse short and long term outcomes compared to a non-­‐diabetic. This is important as T2D status (those not on insulin) are not considered in EUROSCORE. Refining surgical risk based on more discrete classifications of continuous variables is required.

In chapter 2, EPF was dysfunctional and is highly associated with EPF lipolysis in T2D and this may overload the T2D heart with FFA that exceeds its ability to oxidise. Identifying EPF volume may be a sensitive surrogate for LV IMCL and abnormal cardiac energy metabolism. The LV IMCL was higher in T2D versus non-­‐T2D. VDR was significantly associated with IMCL and the majority of IMCL was located close to the myofibrillar T-­‐tubule. The role that VDR/IMCL relationship plays in cellular lipogenesis and calcium metabolism and action potential propagation requires further study. This may be an important mechanism linking abnormal energy metabolism with poor contractile function. We identified that serum β-­‐hydroxybutyrate is a predictor of IMCL. Promoting ketone oxidation (due to its oxygen efficiency) prior to surgery may be protective against ischaemia and reperfusion (I/R) induced myocardial damage.

In chapter 3, RA tissue was exposed to ischaemia and reperfusion in two vitamin D (50nmol/L and 100 nmol/L) doses. Genes controlling energy metabolism were assessed after experimental I/R. Cell viability and injury markers confirmed cell viability. FFA oxidation and PDK was decreased and insulin sensitivity, glucose transport and glucose oxidation increased. None of the gene expression profiles were significant when comparing 50 to 100 nmol/L. This shift in energy substrate <FFA and >glucose oxidation may be beneficial in the I/R period to protect the heart from cellular damage.

Hull York Medical School, The University of Hull and The University of York
Loubani, Mahmoud; Hobkirk, James; Carroll, Sean (Sport scientist)
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