UCL Institute of Cardiovascular Science
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Myocardial protection, Ischaemia-Reperfusion and Conditioning
Heart disease is the leading cause of death and disability in the world. The commonest form of heart disease affects the arteries supplying the heart muscle with blood, termed coronary artery disease (CAD). Blockages and narrowing in these arteries lead to heart muscle damage called ischemic heart disease. Ischaemic heart disease may cause premature death through heart attacks or disability when the heart pump becomes damaged and eventually fails. Investigating novel ways of protecting the heart from coronary artery & ischaemic heart disease is the major research objective of this research theme. The experimental basic science studies undertaken are crucial for identifying novel signalling pathways & targets to protect the heart. In addition, translating our basic science studies to clinical studies, for the benefit of patients, is equally a fundamental part of the research we undertake.
Key research activities
The most powerful strategy for protecting the heart against acute ischaemia-reperfusion injury is to utilize the endogenous mechanisms through which the heart protects itself from extrinsic insults - this phenomenon has been termed ‘conditioning’. Using a translational approach this can be achieved using either mechanical or pharmacological ‘conditioning’ strategies. Studies are undertaken in both the basic science laboratory as well as in the clinical setting of coronary artery bypass surgery and percutaneous coronary intervention.
The ability to dissect the consequences of acute ischaemia-reperfusion on cell function and the need to be able to accurately assess the efficacy of novel cardioprotective strategies is crucially dependent on advanced biological and clinical cardiac imaging technology. Cardiac imaging studies are undertaken in both the basic science laboratory as well as in the clinical setting.
Elucidating the cell signalling pathways underlying cardioprotection has provided insight into the pro-survival signal transduction pathways within the cell and has resulted in the identification of novel pharmacological targets for protecting the heart against acute ischaemia-reperfusion injury.
Mitochondria are the powerhouses of the cell, supplying the energy required for normal heart function. As such preserving mitochondrial function in the heart during acute ischaemia-reperfusion injury is an important therapeutic strategy for cardioprotection.
Mitochondria as targets for cardioprotection Mitochondria are the powerhouses of the cell, supplying the energy required for normal heart function. As such preserving mitochondrial function in the heart during acute ischaemia-reperfusion injury is an important therapeutic strategy for cardioprotection. Co-morbidities and cardioprotection Patients with IHD are likely to have a number of co-morbid conditions at the time of presentation, many of which can influence the sensitivity of the myocardium to certain cardioprotective strategies. Therefore, it is essential to establish whether or not a novel cardioprotective strategy is effective in the presence in one or more of these co-morbidities. In this regard all the above strategies are fundamental to ascertaining how co- morbidities, such as age, diabetes, obesity, affect and influence the cardioprotective properties of the heart.