Skeletal Muscle Mitochondrial Function in Pulmonary Hypertension
Research type
Research Study
Full title
Skeletal muscle mitochondrial biogenesis in patients with Pulmonary Arterial Hypertension
IRAS ID
140807
Contact name
Paul Corris
Contact email
Sponsor organisation
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Research summary
Pulmonary Arterial Hypertension (PAH) is a debilitating disease. There is progressive narrowing of the vessels in the lungs that leads increase in the pulmonary artery pressures placing a strain on the blood pumping action of the right side of the heart leading eventually to right side heart failure. It affects both genders with a female preponderance. Patients present with progressive breathlessness, fatigue and syncope. It results in significant limitation of physical activity and low quality of life.
Management focuses on both supportive therapy and target driven drug therapies. Modern drug therapy has led to a significant improvement in PAH patients’ symptoms and has slowed the rate of clinical deterioration. Exercise training in number of recent studies has been shown to be beneficial in improving quality of life and exercise capacity. Despite the use of medications and exercise, patients remain symptomatic with significant limitation of their physical functioning with a poor prognosis.
Recent clinical studies have demonstrated peripheral muscle changes in PAH patients on muscle biopsies. Mitochondria are the power generating units within cells to produce energy. Studies based on animal models have suggested that peripheral muscle mitochondrial dysfunction occurs earlier than in the right ventricle in pulmonary hypertension.
The aim of the study is to determine at the cellular level of peripheral muscle, mitochondrial respiration and correlating with mitochondrial activity on magnetic resonance spectroscopy in PAH patients. This is a proof of concept research study looking to recruit six idiopathic PAH patients. Each patient will undergo a questionnaire, a 31Phosphororous-Magnetic Resonance Spectroscopy (31P-MRS) scan and a muscle biopsy. The muscle biopsy will look closely at mitochondrial respiration and mitochondrial DNA load. If there is significant mitochondrial dysfunction, it can open up avenues to new trials using resistance training in PAH patients to improve symptoms and function which bring additional benefit to already existing management strategies.REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
13/NE/0353
Date of REC Opinion
17 Jan 2014
REC opinion
Further Information Favourable Opinion