The overall research interests of the Hatter Cardiovascular Institute (HCI) include myocardial protection and the pathophysiology of ischaemia/reperfusion injury. More specifically we focus on developing ways to protect the diabetic and non-diabetic myocardium from the consequences of ischaemic and reperfusion-induced injury. This has involved an understanding of the pathophysiology of ischaemic heart disease at both the cellular, molecular and clinical levels. The HCI is noted for its translational approach to research, incorporating cellular-based models through to the clinical setting.
An important component of our research interests include the concept of “myocardial and remote preconditioning and post-conditioning”, potent endogenous adaptive mechanisms for protecting the heart against ischaemia-reperfusion injury. Concurrently, we are developing new pharmacological and therapeutic strategies to protect the myocardium from reperfusion-induced injury based upon our understanding of pro-survival signal transduction pathways and the contribution of mitochondria to cell survival that can be exploited to the benefit of the patient with ischaemic heart disease.
Complementing our cardioprotection programme are now two additional research arms: (1) neuroprotection specific to ischemic stroke and (2) cancer, investigating how best to reduce the damage to the heart from chemotherapy.
Below is a synopsis of each research programme.
The Hatter Cardiovascular Institute undertakes translational research focusing on the pathophysiology of Ischaemic Heart Disease in the young and aging myocardium in both the normal heart as well as in settings of co-morbidities such as diabetes and the metabolic syndrome. The research undertaken within the HCI explores the treatment strategies for protecting the heart at both a cellular & molecular level as well as in patients at risk of myocardial infarction.
This is undertaken in the purpose built and well-equipped laboratories through a wholly integrated approach employing a variety of experimental models. The research is directly translational, using the primary animal and human cardiomyocyte, the in vitro and in vivo perfused transgenic animal model and human muscle/artery through to clinical studies of patients with coronary heart disease undergoing CABG surgery and primary PCI. In all these settings, basic and clinical scientists focus on identifying the mechanism and signalling pathways associated with cellular injury and protection, with the ultimate aim of identifying new therapeutic targets and agents to protect the heart from acute myocardial infarction.
The Hatter Cardiovascular Institute has initiated a Neuroprotection Group with the aim of using the knowledge we have in the cardiovascular ischaemia-reperfusion field to protect the brain from ischaemic stroke. This has been underpinned by a significant grant via the Hatter Foundation and UCLH Charity.
The management of stroke and acute myocardial infarction are very similar and consist primarily on achieving rapid and complete reperfusion of the ischaemic tissue by endovascular procedures.
This research programme involves working with our colleagues in the HASU (Hyper-Acute Stroke Unit) at UCLH and the UCL Institute of Neurology, establishing animal-based stroke models in the HCI and undertaking clinical research studies at the National Hospital for Neurology and Neurosurgery.
CARDIO PROTECTION FOLLOWING CANCER THERAPY
Cardio-oncology is a rapidly emerging research area. The Hatter Cardiovascular Institute has established a Cardio-Oncology Program which brings together Cardiologists, Oncologists and basic & clinical scientists from the HCI and the Macmillan Cancer Hospital at UCL/UCLH who all work together in promoting the cardiovascular health of UCLH cancer patients.
Our comprehensive cardio-oncology program provides care for patients who may have cardiac side-effects from traditional cancer therapies, such as anthracyclines and radiation, or novel targeted therapies.
This is underpinned by a comprehensive basic & clinical research group whose aim is to use the skills and knowledge obtained in the cardiovascular protection field, to protect the heart of patients on chemotherapy.
The Hatter Cardiovascular Institute actively investigates the role of the inflammatory system as a cause of significant injury during acute myocardial infarction and ischemic stroke. Importantly our research into methods of alleviating the detrimental effects of inflammation are similar to events seen in the early stages of the COVID-19 disease, i.e. the cellular mechanisms are similar to those seen in patients with sepsis. The phenomenon known as “Remote Ischemic Conditioning (RIC)”, which is a simple non-invasive procedure, has been shown to prevent cellular injury, including those associated with sepsis. Therefore, based on the evidence from studies investigating sepsis, it is hypothesised that the same benefit would be seen in patients diagnosed with COVID-19.
With our extensive knowledge and experience in cellular protection, The Hatter Cardiovascular Institute therefore joined researchers worldwide in turning their attention to COVID-19 and are leading a study investigating the potential for RIC to reduce the severity of anti-inflammatory cytokines which are responsible the so-called cytokine “storm” that occurs in COVID-19 patients. The study, titled ‘Can Remote Ischaemic Conditioning Reduce Inflammatory Markers in COVID-19 Patients – A Randomised Pilot Study,’ (see announcement study below) was approved by UCLH and the National Research Ethics Boards in April 2020.
With an aim to develop new methods to reduce the heightened inflammatory response, we hope to be able to halt, or at least attenuate, the COVID-19 disease process before patients enter intensive care, when the situation changes dramatically and may be too late.
We are actively working with colleagues in Brazil and South Africa to expand the research programme and better understand the application to populations worldwide. We are grateful to the Thompson Family Trust for their generous support of our international COVID-19 research.