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Investigating the protective role of nitrite against myocardial ischaemia reperfusion injury

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

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 early mortality, nevertheless the associated myocardial injury frequently leads to the development of heart failure, that may develop either soon or a long time after the triggering event. Whilst prompt reperfusion is a prerequisite to limit myocardial injury, paradoxically the process of reperfusion itself causes myocardial injury - a phenomenon called ischaemia-reperfusion injury (IRI). In addition to prompt reperfusion (usually by percutaneous coronary intervention (PCI)) there is an urgent need for effective adjunctive therapies that limit myocardial injury due to IRI.

Nitrite is an important physiological mediator under hypoxic and acidic conditions. In experimental studies, it has been shown that nitrite protects against myocardial ischaemia reperfusion injury. In man, we have demonstrated that nitrite improves cardiac function. However, despite these promising findings, the mechanisms by which nitrite-mediates protection remains to be elucidated. We will extend this work to investigate the mechanisms by which nitrite protects the heart against reperfusion injury. This study will use a broad range of techniques, such as Langendorff model, isolated cardiomyocytes, and various molecular techniques.


To apply, please submit your CV and a covering email/letter for consideration by Dr Melanie Madhani ()
Applicants should have a strong background in biology, molecular biology, cell biology or medical sciences and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject. A Masters degree in research or experience in the techniques outlined within this application, whilst not a necessity, would be highly advantageous. It will be desirable to have a commitment to cardiovascular research.


For more information about the Madhani research group and Institute of Cardiovascular Sciences please see:

http://www.birmingham.ac.uk/staff/profiles/cardiovascular-sciences/Madhani-Melanie.aspx

http://www.birmingham.ac.uk/research/activity/cardiovascular-sciences/research/cardiovascular-translational-group-myocardial/index.aspx

http://www.birmingham.ac.uk/research/activity/cardiovascular-sciences/index.aspx

Funding Notes

Self-funded PhD students Only
We will only consider applications from prospective students with:
- a good biomedical degree, with interests in any of the areas outlined in the project,
- good command of the English language as outlined in the postgraduate prospectus,
- a source of funding to cover tuition fees and bench fees.

References

Loudon BL, Noordali H, Gollop ND, Frenneaux MP and Madhani M. Present and Future Pharmacotherapeutic Agents in Heart Failure: An Evolving Paradigm. British Journal of Pharmacology. 2016 Mar 18
Arif S, Borgognone A, O’Sullivan A, Lai E, Menon A, Sharma V, Beadle R, Feelisch M, Horowitz J, Bonser RS, Frenneaux MP and Madhani M. Role of aldehyde dehydrogenase in hypoxic vasodilator effects of nitrite in humans. British Journal of Pharmacology. 2015. July: 172 (13):3341-52.
Ormerod JOM, Arif S, Mukadam M, Evans JDW, Beadle R, Fernandez BO, Bonser RS, Feelisch M, Madhani M*, Frenneaux MP* - *joint last authors. Short-term intravenous sodium nitrite infusion improves cardiac and pulmonary hemodynamics in heart failure patients. Circulation Heart Failure. 2015 May: 8(3): 565-71.
Bailey JC, Feelisch M, Horowitz JD, Frenneaux MP and Madhani M. Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation. Pharmacol Ther. 2014 Jun 30.

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