Cardiovascular Translational Group:
Myocardial Infarction and Heart Failure

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Group leader: Dr Melanie Madhani

Overview

The main aim of our research is to characterise the functional deterioration within the heart and vasculature following myocardial infarction and heart failure and to assess pharmacological methods of improving outcomes.

Our research group

Despite advances in both knowledge and technology, coronary heart disease is the most common cause of death worldwide. Currently, substantial expenditure in the health service is directed towards restoring blood flow in patients with acute myocardial infarction (AMI) in order to limit myocardial injury. Whilst this has substantially reduced mortality, nevertheless the associated myocardial injury frequently leads to the development of heart failure that may develop either soon or after the index event. Our research group is interested to understand the mechanisms of myocardial injury during ischaemia and reperfusion and how this affects vascular functions. Of particular interest is to understand the physiological and pathological actions of nitrite. Currently, we have a broad range of translational research taking place in our group to investigate the role of nitrite therapy from “bench to bedside”:

Basic and Clinical Translational Research:

  • Investigation of novel cardioprotective strategies and the role of nitrite in cardioprotection from bench to bedside (patients undergoing coronary artery bypass grafting surgery)
  • Assessment of vascular dysfunction in heart failure
  • Effect of cardiovascular disease on myocardial cellular signalling
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Current Projects

  • Effects of nitrite on cardiac muscle: Physiology, Pharmacology and Therapeutic Potential (Medical Research Council funded, led by Prof Frenneaux)
  • Nitrites in heart failure (British Heart Foundation funded, led by Prof Frenneaux and Dr Madhani)
  • Effects of glucose-insulin-potassium therapy in patients undergoing coronary artery bypass graft (CABG) surgery (University Hospitals Birmingham Charities funded, led by Dr Melanie Madhani)
  • Effects of natriuretic peptides on platelet function (British Heart Foundation funded, led by Dr Melanie Madhani, Prof Adrian Hobbs and Prof Steve Watson)
  • Effects of a modest reduction in renal function on cardiovascular structure and function: a study of kidney donors (BHF funded led by Dr Moody, Dr Townend, Dr Madhani and Dr Ferro)

Recent Publications

Please view a full list of Dr Madhani’s publications

Borgognone A, Shantsila E, Worrall SM, Prompunt E, Loka T, Loudon BL, Chimen M, Rainger GE, Lord JM, Turner A, Nightingale P, Feelisch M, Kirchhof P, Lip GYH, Watson SP, Frenneaux MP, Madhani M. Nitrite circumvents platelet resistance to nitric oxide in patients with heart failure preserved ejection fraction and chronic atrial fibrillation. Cardiovasc Res. 2018 Apr 12.

Sutton TR, Minnion M, Barbarino F, Koster G, Fernandez BO, Cumpstey AF, Wischmann P, Madhani M, Frenneaux MP, Postle AD, Cortese-Krott MM, Feelisch M. A robust and versatile mass spectrometry platform for comprehensive assessment of the thiol redox metabolome. Redox Biol. 2018 Jun;16:359-380. doi: 10.1016/j.redox.2018.02.012. Epub 2018 Feb 19.

Schwarz K, Singh S, Parasuraman SK, Rudd A, Shepstone L, Feelisch M, Minnion M, Ahmad S, Madhani M, Horowitz J, Dawson DK, Frenneaux MP. Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial. J Am Heart Assoc. 2017 Sep 8;6(9). pii: e006478. doi: 10.1161/JAHA.117.006478.

Noordali H, Loudon BL, Frenneaux MP, Madhani M. Cardiac metabolism - A promising therapeutic target for heart failure. Pharmacol Ther. 2018 Feb;182:95-114. doi: 10.1016/j.pharmthera.2017.08.001. Epub 2017 Aug 15.

Loudon BL, Noordali H, Gollop ND, Frenneaux MP, Madhani M. Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm. Br J Pharmacol. 2016 Jun;173(12):1911-24. doi: 10.1111/bph.13480. Epub 2016 May 6.

Ormerod JO, Arif S, Mukadam M, Evans JD, Beadle R, Fernandez BO, Bonser RS, Feelisch M, Madhani M, Frenneaux MP. Short-term intravenous sodium nitrite infusion improves cardiac and pulmonary hemodynamics in heart failure patients. Circ Heart Fail. 2015 May;8(3):565-71. doi: 10.1161/CIRCHEARTFAILURE.114.001716. Epub 2015 Apr 2.

Dautov RF, Stafford I, Liu S, Cullen H, Madhani M, Chirkov YY and Horowitz JD. Hypoxic potentiation of nitrite effects in human vessels and platelets. Nitric Oxide. 2014 August; (40) 36-44.

Siddiqi N, Bruce M, Neil CJ, Jagpal B, Maclennon G , Cotton SC, Papadopoulo SA, Bunce N, Schwarz LPK, Singh S, Hildick-Smith D, Horowitz JD, Madhani M, Boon N, Kaski JC, Dawson D and Frenneaux MP. Intravenous sodium nitrite in acute ST elevation myocardial infarction: a randomised controlled trial (NIAMI). European Heart Journal 2014 May 14; 35(19):1255-62.

Staff

Principal Investigators
Dr Melanie Madhani

Postdoctoral Researchers
Dr Jenna Bailey - Medical Research Council Research Fellow
Dr Alessandra Borgognone - British Heart Foundation Research Fellow

Internal Collaborators
Professor Steve Watson - British Heart Foundation Professor in Cardiovascular Sciences and Cellular Pharmacology
Dr Charles Ferro - NIHR Fellow and Consultant Nephrologist, Birmingham Cardio-Renal Group
Dr John Townend - Honorary Reader in Cardiology and Consultant Cardiologist, Birmingham Cardio-Renal Group

BCRG PhD Student
Dr William Moody - British Heart Foundation Clinical Research Fellow and SpR in Cardiology

Cardiac Surgeons
Mr Nigel Drury - Honorary Clinical Lecturer. University of Birmingham
Mr Jorge Mascaro - Consultant, University Hospitals Birmingham NHS Trust, UK
Ms Ashvini Menon

External Collaborators
Regius Professor Michael Frenneaux - School of Medicine and Dentistry, University of Aberdeen, UK
Professor Adrian Hobbs - Barts and The London School of Medicine and Dentistry at Queen Mary, London, UK
Professor John Horowitz - University of Adelaide, South Australia, Australia
Professor Malcolm Underwood - The Chinese University of Hong Kong, Hong Kong