Adaptive Mechanisms of the Heart to Ischaemic Stress
Background The response of the human heart to ischaemic stress is not uniform and adaptive mechanisms play a role in attenuating myocyte damage and improving performance. The mechanisms of such adaptations are poorly understood and likely multifactorial. The main aim of this thesis was to examine these mechanisms using the models of exercise induced myocardial ischaemia and acute myocardial infarction Methods Using a specially adapted supine ergometer, we used invasive physiological measurements and high-resolution cardiac magnetic resonance imaging to assess changes in coronary blood flow, central haemodynamics and transmural myocardial perfusion during exercise. In a separate group, we sought to examine the role of post-conditioning as a potential therapeutic tool in a randomised controlled trial involving patients undergoing primary percutaneous revascularisation for acute myocardial infarction. Results We were able to demonstrate that the reduction of ischaemia seen on second exercise in patients with stable coronary artery disease is associated with synergistic changes in central and coronary haemodynamics, with a fall in myocardial microvascular resistance and enhanced vascular-ventricular coupling. High-speed CMR perfusion imaging using k-t acceleration is a feasible tool to investigate these differences, with sufficient spatial resolution to detect transmural flow heterogeneity. The data from the postconditioning study did not show a difference in infarct size between the groups but numbers were small. Conclusion The mechanisms of adaptation of the heart to ischaemic stress are complex and likely multifactorial. These results suggest that synergistic changes in systemic and coronary circulations as part of a generalised reactive hyperaemic vasodilatory response to exercise results in improved myocardial perfusion and overall performance. Transmural flow redistribution to the subendocardium is likely to play an important role in attenuating myocardial ischaemia on repeat exercise although we await the results of ongoing work. Innate myocardial protection, such as that afforded by postconditioning remains a possibility, although the results from this study are inconclusive.
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