Clinical research techniques commonly used in our research facility:

Blood Pressure (BP)

• Semi-automated oscillometric BP
• Auscultatory BP
• Exercise BP
• 24 h ambulatory blood pressure monitoring

Portable, automated blood pressure monitors can be used to record blood pressure over a set-period of time (usually 24 hours), with chosen time-intervals. Output includes systolic, diastolic, mean, and central blood pressures during the day-time and the night-time.

Central blood pressure and wave reflection

• Pulse wave analysis (PWA)

Several parameters can be derived from PWA; central systolic, diastolic and mean pressure and, augmentation index which is a composite measure of arterial stiffness and wave reflection.

Arterial stiffness

We can assess arterial stiffness non-invasively using variety of commercially available systems.

• Pulse wave velocity (PWV)

PWV is a measure of regional arterial stiffness. PVW is measured by recording simultaneous waveforms from two locations (usually from carotid and femoral arteries), or by sequentially recording the waveforms from two locations and using the R wave of the ECG to gate the two successive readings.

• Distensibility and Compliance

Carotid and/or brachial artery diameter is measured using high-resolution vascular ultrasound with a real-time analyser, and continuous BP is simultaneously recorded in order to calculate vascular distensibility and compliance.

Cardiac output and stroke volume

CO and SV can be assessed non-invasively using an inert gas rebreathing technique (InnoCor) Briefly, while resting, subjects continuously re-breaths a gas mixture and expired gases are sampled continuously and analyzed by an infrared photoacoustic gas analyser for the determination of CO and SV. In combination with measurement of mean arterial pressure (from PWA), the peripheral vascular resistance can be calculated. We can also assess cardiodynamic parameters, such as CO, CI, SV using non-invasive thoracic impedance cardiography.

Venous occlusion Plethysmography

Forearm blood flow (FBF) can be measured using the technique of venous occlusion plethysmography. The principle of this technique is as follows; a cuff is inflated around the upper arm in order to allow arterial flow into the forearm, but to prevent the venous return. This results in a linear increase in forearm volume over time, and this is proportional to arterial blood inflow until venous pressure rises towards the occluding pressure. This technique can be used to assess:

• Effect of vasoactive drugs or compounds
• Endothelial Function
• Venous Capacitance
• Capillary Filtration
• Minimum Vascular Resistance

Aellig hand vein test

This technique is used for determining dorsal hand vein diameter and can be used to produce dose-response curves for vasoactive drugs after direct local infusion. The internal diameter of the vein, distended by inflation of an upper arm cuff to 40mmHg, is measured by a light-weight magnetized rod resting on the summit of the vein.

 12-lead electrocardiogram

The standard 12-lead ECG is used to assess the electrical activity of the heart and is recorded from electrodes placed on the subject chest.

Vascular and cardiac sonography

• Carotid IMT

Carotid IMT can be measured non-invasively using a high resolution ultrasound scanner with build-in analysing software.

• Endothelial Function

Endothelial function can be assessed non-invasively using the technique of flow mediated dilatation (FMD), where endothelium-dependent dilatation in the brachial artery is assessed during reactive hyperaemia in response to 5 minute arterial occlusion and endothelium-independent dilatation in response to sublingual glyceryl trinitrate, using high-resolution vascular ultrasound and a real-time analyser that measures arterial diameter and Doppler flow.

• Transthoracic Echocardiogram

Echocardiograms are performed by qualified cardiac physiologists and provide a full clinical report of cardiac structure and function.

 

 Exercise testing

• Haemodynamic profiling during exercise

A full haemodynamic profile during exercise can be produced using a cycle ergometer or treadmill during standardised protocols. A commercially available system is used to assess gas exchange parameters including O₂ uptake (VO₂), CO₂ excretion (VCO₂) and minute ventilation (V_E). This enables the determination of maximum oxygen uptake (MVO₂), a measure of aerobic ‘fitness’. Cardiac output and stroke volume are assessed non-invasively using inert gas rebreathing technique and blood pressure measured using specialised BP monitor.

• Max testing
• Sub-maximal testing
• Short physical performance battery
• Six minute walk test (6-MWT)

6-MWT is a measure of functional limitation. It is a simple, self-paced exercise test, where patients are asked to walk at their own pace for 6 minutes, including breaks if necessary. Total distance walked is recorded.

Autonomic Function testing

• Heart rate variability (HRV)

Heart rate variability is a non-invasive measure of autonomic function. HRV is assessed by recording of R-R intervals via 3-lead ECG; the recording is then subjected to statistical analysis in order to obtain spectral and time-domain analysis of HRV.

• Baroreflex

We can perform full autonomic function testing including tilt table and coldpressor tests, Valsalva manoeuvre, catecholamine or tyramine infusion test in collaboration with Dr Johann Graggaber/ NHS.

Pulmonary function

• Lung capacity

Tests are performed using a handheld calibrated spirometer and provide flow-loop curves and results print out with absolute and percentage predicted values of Forced Expiratory Lung Volume in 1 second (FEV1) in 1 second and Forced Vital Capacity (FVC).

• Sniff nasal inspiratory pressure (SNIP)

SNIP is a simple and non-invasive measure of diaphragmatic muscle strength. A nasal bung is placed in the nostril and maximum nasal pressure during forced inspiration is recorded.

Body Composition

• Skinfold calliper
• TANITA bioimpedence scales

Biological sampling

We have Facilities for blood and urine collection and handling, including 24 h urine collections.

Clinical proteomics

We employ a variety of state-of-the-art proteomics technologies for biomarker discovery or assay, protein quantitation in small volume samples, and determination of tissue protein expression. We employ Parallel Reaction Monitoring (PRM, also known as multiple reaction monitoring or MRM) on an Orbitrap nano-ESI Q-Exactive instrument, and perform label free methods including SWATH on Orbitrap and ABSCIEX 6600 instruments.

Imaging

We have established strong links with MRI, PET/CT and SPECT units in Cambridge and elsewhere, and have extensive experience in aortic and lung inflammation and  calcification imaging, and assessment of PWV using MRI. These have been utilised in proof of concept  trials to determine the effect of novel agents on disease  pathophysiology and to better understand the effects of such agents. We have had experience in conducting multi-centre clinical trials across the UK utilising imaging  biomarkers to aid drug development.