Mechanisms of right ventricular adaptation to pressure overload v1
Research type
Research Study
Full title
Molecular mechanisms of right ventricular adaptation to increased afterload
IRAS ID
129173
Contact name
Joanna Pepke-Zaba
Contact email
Sponsor organisation
Papworth Hospital NHS Foundation Trust
Research summary
Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease characterised by raised blood pressure in the blood vessels in the lungs (pulmonary arteries). It is caused by scarred clots in those blood vessels. Patients with CTEPH have changes to the right side of their hearts (right ventricle) to compensate for the higher pressures. These adaptations include thickening of the wall of the heart to allow the heart to pump blood more effectively. However, over time these adaptive mechanisms fail. The heart is then unable to pump blood effectively; this is known as right heart failure. Right heart failure is the commonest cause of death in patients with CTEPH.
Pulmonary endarterectomy is a potentially curative operation for CTEPH. During the operation the clots in the lungs are removed. This helps to reduce the pressure in the pulmonary arteries and reduce the strain on the heart. It is only performed at Papworth Hospital in the UK.
Gene expression (which genes are switched on and off) forms a set of instructions for how cells function. Therefore, changing gene expression can alter cellular function. We believe that the response of the right ventricle to increased blood pressure in the lungs is determined by the gene expression profile in the cells of the heart.
We propose to take a small sample from the right side of the heart at the time of surgery. These samples will be analysed to identify changes in gene expression. We hope this would lead to a better understanding of how the heart works and new treatments for heart failure.
We also intend to measure cytokines (small molecules responsible for passing messages between cells in the body) in these patients before and after surgery. We believe these molecules also have a role in adaptation of the heart to increased pressure in the pulmonary arteries.
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
13/EE/0331
Date of REC Opinion
6 Dec 2013
REC opinion
Further Information Favourable Opinion