Lab Overview

Consultant Cardiologist at Bristol Heart Institute and Clinical Senior Lecturer at University of Bristol.

Leader of Bristol Cardionomics Research Group with Dr Emma Hart.

Aim: To investigate mechanisms involved in the development of hypertension and transition to heart failure and so develop novel therapies to improve outcomes for patients.

Research Questions

The key questions that we are trying to address focus on the role the sympathetic nervous system in hypertension and heart failure:

1. Why do young people develop high blood pressure?
   1. Role of carotid body to drive sympathetic activation
   2. Imaging to identify novel targets such as cerebral vascular anomalies
2. What are the mechanisms contributing to drug resistant hypertension?
   1. Investigating novel molecules to block P2X3 receptors.
3. Why do some people with high blood pressure go on to develop heart failure?
   1. Role of inflammation and fibrosis.
4. How do cerebral vascular anomalies affect control of blood pressure?
   1. Young onset hypertension and following acute aortic dissection repair.
5. What is the role of sympathetic activation in heart failure?
   1. Mechanisms including metaboreflex, chemoreflex, inflammation and fibrosis.
   2. Effects of iron deficiency
   3. Exercise training and cardiac rehabilitation
   4. Cardiac imaging with echo and MRI

Techniques

Our clinical physiology lab is run by Dr Emma Hart at the Clinical Research Imaging Centre in Bristol.

The main techniques that are in use in our lab are:

• Microneurography
  • This is a way of directly recording sympathetic nerve activity that is directed towards blood vessels supplying skeletal muscle
• Autonomic function testing
  • Baroreflex sensitivity and heart rate variability
  • Carotid body chemoreflex testing
  • Muscle metaboreflex testing
• Cardiopulmonary exercise testing
• Echocardiography, including stress echo, to assess systolic and diastolic function

Impact

Our group has pioneered the mechanistic understanding of the role of carotid body in contributing to sympathetic activation in hypertension. We have translated the basic science work of Professor Julian Paton on carotid body dysfunction. In collaboration with groups in Poland and St Bartholomew’s Hospital in London we have demonstrated that carotid body modulation is a potential treatment option for resistant hypertension and heart failure.

Our group runs regular blood pressure awareness days in Bristol and businesses and in public spaces helping over 500 people to “Know their BP number”.

We have taken part in public engagement activities such as participating in Pint of Science.

Selected Publications

• Chant B, Bakali M, Hinton T, Burchell AE, Nightingale AK, Paton JFR, Hart EC.  Antihypertensive Treatment Fails to Control Blood Pressure During Exercise.  Hypertension. 2018 Jul;72(1):102-109.  doi: 10.1161/HYPERTENSIONAHA.118.11076. PubMed PMID: 29895532.
• Warnert EA, Rodrigues JC, Burchell AE, Neumann S, Ratcliffe LE, Manghat NE, Harris AD, Adams Z, Nightingale AK, Wise RG, Paton JF, Hart EC.  Is High Blood Pressure Self-Protection for the Brain?  Circ Res. 2016 Dec 9;119(12):e140-e151.  Epub 2016 Sep 26.  PubMed PMID: 27672161.
• Pijacka W, Moraes DJ, Ratcliffe LE, Nightingale AK, Hart EC, da Silva MP, Machado BH, McBryde FD, Abdala AP, Ford AP, Paton JF.  Purinergic receptors in the carotid body as a new drug target for controlling hypertension.
• Nat Med. 2016Oct;22(10):1151-1159.  doi: 10.1038/nm.4173. Epub 2016 Sep 5.  PubMed PMID: 27595323; PubMed Central PMCID: PMC5750397.
• Narkiewicz K, Ratcliffe LE, Hart EC, Briant LJ, Chrostowska M, Wolf J, Szyndler A, Hering D, Abdala AP, Manghat N, Burchell AE, Durant C, Lobo MD, Sobotka PA, Patel NK, Leiter JC, Engelman ZJ, Nightingale AK, Paton JF.
• Unilateral Carotid Body Resection in Resistant Hypertension: A Safety and Feasibility Trial.  JACC Basic Transl Sci. 2016 Aug 29;1(5):313-324. eCollection 2016 Aug.  PubMed PMID: 27766316; PubMed Central PMCID: PMC5063532.
• Paton JF, Sobotka PA, Fudim M, Engelman ZJ, Hart EC, McBryde FD, Abdala AP, Marina N, Gourine AV, Lobo M, Patel N, Burchell A, Ratcliffe L, Nightingale A.  The carotid body as a therapeutic target for the treatment of sympathetically mediated diseases. Hypertension. 2013 Jan;61(1):5-13.  doi:10.1161/HYPERTENSIONAHA.111.00064. Epub 2012 Nov 19.

View complete publications list in the University of Bristol publications system.

Funding

2018     £100,000. CI - British Society of Heart Failure. 2 years. Does iron deficiency drive autonomic dysfunction in patients with chronic heart failure?

2016     £65,000. CI - Small Business Research Initiative / Folium Optics. Clinical Trial: “My Health Tag: Improving compliance in chronic heart failure”

2015     £20,000. CI - Above and Beyond.  Pilot study: “Effects of minocycline on the sympathetic nervous system in chronic heart failure.”

2014     £93,000. Co-PI – Medtronic. 3 years. Clinical trial: “Renal Denervation: Measuring Procedural Success in Human Hypertensive Patients.”

2013     £180,000. Co-PI – Cibiem. 2 years’. Clinical trial: “Carotid body resection for treating refractory hypertension.”

2013     £283,031. Co-applicant - NIHR-HTA. 18 months. Grant: “Monitoring patients with chronic heart failure.” Role of BNP.

2012     £190,000. Co-PI - Coridea (Venture Capitalist) 2 years. Funded basic science animal and human translational studies in hypertension.

2012     £140,000. Co-PI - Coridea (Venture Capitalist) 3 years. Clinical Research Fellowship:  Chemosensitivity in refractory hypertension: a clue for a novel treatment?” (Dr Laura Ratcliffe)

2012     £160,000 . Co-PI – UHBristol. 3 years. Clinical Research Fellowship: “The enigma of renal nerve denervation for hypertension.” (Dr Amy Burchell)

Teaching

MB18 - Lectures and small group teaching to years 1/2/3/5 on cardiology and imaging

MB21 - Cardiology Case lead for chest pain years 1 and 2 Lectures on chest pain and arrhythmias

PPN - Lectures to final year students on autonomic function and the cardiovascular system

MSc - Lectures to t translational cardiovascular medicine students on heart failure

Lectures to perfusion students on heart failure

eSSC - supervising 4-5 students per year on heart failure and hypertension topics

Citizenship

Cardiology Teaching in Mbarara University Hospital Uganda – 2 visits to set up echo department and train cardiologists/physicians. Also Training the Teachers in Uganda – teaching the general medicine registrars on educational theory and practice.

Mentoring for 2 cardiologists in Mbarara, Uganda and Kisiizi, Uganda. Providing supervision and mentoring when they have come to Bristol to consolidate their echo and cardiology skills. Regular Skype meetings and review of complex echo cases.