Coronary heart disease (CHD) is the leading cause of death in the UK, accounting for 105,000 deaths in 2004 and costing the UK economy in excess of £7.9 billion a year. Innovative treatment strategies are required to improve health outcomes in patients with CHD. The Hatter Cardiovascular Institute at UCL has been undertaking translational studies to try and address this issue. In this regard experimental basic laboratory studies have identified two novel targets for cardioprotection: (a) the mitochondrial permeability transition pore (mPTP), a mitochondrial channel whose opening induces cardiomyocyte death at the onset of myocardial reperfusion but can be prevented using the immunosupressent cyclopsorine-A in animals & man (b) the Reperfusion Injury Salvage Kinase (RISK) pathway, a group of endogenous pro-survival protein kinases which when activated at the onset of reperfusion, reduce myocardial injury. In addition our experimental studies have also identified specific pharamcological agents which directly target the RISK pathway and the mPTP.

Our clinical research programme, emanating from our basic science studies, cross-cuts the research themes of Cardiovascular and Imaging, and involves active collaborations across the Academic Health Sciences Partnership and other London hospital Trustee below. Based directly on our preclinical observations, we are currently investigating new and specific treatment strategies for reducing myocardial injury and improving clinical outcomes in patients with CHD, focusing on those AMI patients undergoing percutaneous coronary intervention (PCI) and patients undergoing coronary artery bypass graft (CABG) surgery. These new treatment strategies include: (1) Remote ischaemic conditioning (RIC), which describes the cardioprotection obtained from inducing brief ischaemia-reperfusion to the upper limb, using a blood pressure cuff applied to the upper arm. Paramedics from LAS have been administering the RIC protocol to AMI patients in the ambulance. We have recently demonstrated that RIC reduces myocardial injury in CABG patients - we now intend to determine whether RIC can improve clinical outcomes in CABG patients in a London-wide multicentred study; (2) Erythropoietin (EPO), a haemopoietic agent, which is capable of reducing myocardial infarct size by 40-50% through the activation of the RISK pathway. (3) Cyclosporin-A (CsA). We are organising an Europe-wide multi-centred clinical study to determine whether CsA can improve clinical outcomes in AMI patients undergoing PPCI. We will be assessing cardioprotection in AMI patients in terms of myocardial infarct size, microvascular obstruction, and LV function using cardiac MRI.