None listed
Conditions
Brief summary
OCT has been used for decades in ophthalmology to visualise small blood vessels at the back of the eye (retina), but we have recently modified it and developed breakthrough and novel ways to assess the diameter, velocity and blood flow through blood vessels in the skin that are around the size of a human hair. Microdialysis is a technical approach that involves embedding a small plastic tube containing a semi-permeable membrane beneath the skin surface. This permits delivery of very small doses of specific drugs directly into a small patch of human skin, above which imaging is performed. The delivery of these drugs, which stimulate or block specific biochemical pathways, provides a way to study individual mechanisms that may be responsible for microvascular dysfunction and cardiovascular disease development in humans. This approach is sometimes referred to as pharmaco-dissection. By combining microdialysis with OCT imaging, we will establish an unprecedented and powerful new platform to provide insights into the specific physiological mechanisms controlling microvascular function in humans.
Interventions
We recently developed a new technique called optical coherence tomography (OCT) to assess the diameter, velocity and blood flow through blood vessels in the skin that are around the size of a human hair. Two sterile microdialysis fibres (CMA Microdialysis Research AB, Stockholm, Sweden) will be inserted into a small patch of skin at the ventral forearm (30mm), spaced at least 4 cm apart. A microdialysis fibre is a small diameter (~26 Standard Width Gauge or 0.45mm outer diameter) sterile plastic tube containing a 10mm semi-permeable membrane that, when embedded in the skin, allows substances to pass into the tissue fluid. Microdialysis involves the initial insertion of a sterile 21-gauge introducer needle into a small patch of skin (~30mm). A 26G microdialysis fibre, which contains a small (10mm) permeable membrane, is then threaded through this needle, and the 21G needle is removed to leave the plastic microdialysis probe embedded in situ. This tube is continuously perfused at a low flow rate (1–2 µL/min) with a sterile physiological solution (Ringer’s) until this solution is replaced with a pharmacological agonist or antagonist, which diffuses into the small localised area of skin. Changes microvascular in blood flow ensue. This procedure is performed after the skin is anaesthesised using the application of ice for a period of ~10 minutes. Participants typically do not report feeling any sensation during this procedure. To minimise the impact of needle insertion a recovery period (60 minutes) is observed before drug infusion via the microdialysis probe. Optical coherence tomography (OCT) and laser Doppler flowmetry scans are performed on the surface of the skin overlying the section of the probe that is embedded in the skin. Miochol-E Acetylcholine (ACh) cutaneous infusion In this current study, a conservative concentration of 10 mM ACh will be delivered at a low infusion rate of 2 µL/min. Sodium Nitroprusside (SNP) cutaneous infusion In this current study, a conservative concentration of 28 mM SNP will be delivered at a low infusion rate of 2 µL/min. All these medication will be administered by trained researcher at UWA cardiovascular research group, The total duration of the intervention is 3 hours.
Sponsors
Study design
Eligibility
Inclusion criteria
• No history of cardiovascular diseases. • No prescribed medications for any chronic medical conditions. • Blood pressure in the normal range (SBP<140mmHg, DBP18.5 and <30
Exclusion criteria
• Current smoking (or vaping) or a recent history (past 12 months) of smoking or vaping. • Participants with any history of, or current skin diseases.