Effects of neuronal nitric oxide synthase on human cardiac function
Research type
Research Study
Full title
Investigation of the effects of neuronal nitric oxide on human cardiac function in vivo
IRAS ID
171127
Contact name
Ajay Shah
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
The study involves the detailed measurement of the heart's pumping function in subjects with normal hearts or heart failure. Studies will only be carried out
in patients already undergoing cardiac catheterisation in our department for clinical reasons. Cardiac catheterisation is an X−ray based investigation which involves introducing small diameter catheters to the heart in order to image the coronary arteries, assess the pumping action and valve function of the heart, and measure the pressure in the heart's chambers. The catheters are introduced via the femoral or radial artery and the femoral or antecubital vein under local anaesthetic and using light sedation according to the patient's preference.Participation in the study involves introducing a specialized catheter into the main pumping chamber of the heart (left ventricle). This catheter is very similar to those used in routine clinical practice but is able to measure the pressure and volume of the left ventricle with great accuracy. Measurements will be taken in the
resting state and after temporarily increasing the work of the heart by increasing the heart rate with a temporary pacemaker wire. Both of these manoeuvres are widely used in clinical practice for diagnostic and therapeutic purposes. During the measurement period, subjects will receive infusions of a short acting agent (S−methyl−L−thiocitrulline, or SMTC) to specifically inhibit the production of Nitric Oxide (NO) via the enzyme neuronal Nitric Oxide Synthase (nNOS). SMTC will be infused into the heart's blood supply via the catheter used in the clinical catheterisation procedure.
By obtaining measurements in the different groups of participants in the presence and absence of SMTC, we will be able to determine how nNOS−derived NO contributes to the heart's performance in health and disease.In previous studies, we have administered SMTC into the heart’s blood supply in patients in an identical manner and using identical doses, without any problems – so we know that this is safe. However, these previous studies measured coronary flow and not heart function as in the current study
REC name
London - Dulwich Research Ethics Committee
REC reference
15/LO/1110
Date of REC Opinion
6 Aug 2015
REC opinion
Further Information Favourable Opinion