How is it measured?

• The FMSF technique measures changes in the intensity of NADH fluorescence from the skin on the forearm as a function of time, in response to blocking and releasing blood flow in the forearm.
• Blood flow in the forearm is blocked using a typical occlusion cuff, as used to measure blood pressure.

Advantages of FMSF method

• useful for assessing circulatory status by comparing the vascular response to reactive hyperemia (PORH) to the resting state (before occlusion),
• suitable for assessing the degree of ischemia and reperfusion in skin cells depending on blood flow in the vessels,
• useful for assessing the progress and remission of microcirculation disorders, metabolic regulation and vascular complications,
• optimal for the observation of microcirculation oscillations, the amplitude and frequency of which may signal irregularities in the microcirculation,
• helpful for monitoring vascular circulation disorders and selecting individualized forms of therapy.

The FMSF method enables disorders to be detected at an early stage of development and monitoring of the treatment process. It helps to identify patients in possible need of preventive or therapeutic interventions, who may be referred for further diagnosis.

The FMSF-PORH (Flow Mediated Skin Fluorescence-Post Occlusive Reactive Hyperemia) test is based on analysis of ischemic and hyperemic responses and microcirculatory oscillations.

The test enables non-invasive assessment of vascular circulation and/or metabolic regulation. It measures stimulation of the circulation in response to reactive hyperemia. An occlusion cuff, commonly used to measure blood pressure, is used to induce reactive hyperemia (PORH). The test enables assessment of both vasoconstriction and vasodilation. The kinetics of changes in response to reactive hyperemia can also be monitored. The FMSF-PORH test can be used to monitor the treatment process, observe the effects of drugs on vascular health, and track the effects of training and exercise on overall health.

Main parts of a typical trace recorded for an individual patient using AngioExpert

• Baseline – collected for 3 min (or 4 min if unstable).
• Ischemic response (IR) – 3 min occlusion with cuff inflated to 60 mmHg above systolic blood pressure, resulting in an increase of NADH fluorescence.
• Hyperemic response (HR) caused by releasing pressure in the occlusion cuff – NADH fluorescence decreases below the baseline, reaching a minimum followed by a return to the baseline.
• Hyperemic response (HR) with two distinct phases:
  • hyperemia – related to a sharp drop in NADH fluorescence for 20–30 s;
  • reperfusion – a much slower return to the baseline.
• Microvascular oscillations on the baseline and the hyperemic response line express the efficacy of vascular-metabolic regulation related to microvascular dermal flow. A weakening of their amplitude and changes in frequency may indicate the presence of microvascular dysfunction.

Definition of measured parameters

• Hyperemic response parameters HR_max and HR_index express changes in NADH fluorescence (mainly from the keratinocytes in the epidermis) and determine the metabolic reaction of the skin cells to hyperemia and reperfusion.
• Ischemic response parameters IR_max and IR _index express changes in NADH fluorescence (mainly from keratinocytes in the epidermis) and determine the sensitivity of skin cells to hypoxia caused by blocking blood flow in the forearm. This sensitivity is determined primarily by the efficiency of oxygen transport to the epidermal cells just before occlusion.
• The RHR (Reactive Hyperemia Response) parameter characterizes the ischemic and hyperemic responses. It reflects vascular endothelial function related to nitric oxide (NO) production in blood vessels, due to occlusion-induced hyperemia. The RHR parameter is the sum of the IR_max + HR_max parameters.

Interpretation of the measured parameters

• The key parameter for analysis of the ischemic and hyperemic responses is the RHR. The RHR parameter characterizes vascular status based on NO bioavailability mainly in large and medium-sized arteries as a result of transient ischemia. It enables sensitive assessment of the state of vascular circulation.
  The following ranges in the RHR parameter are distinguished:

  RHR > 35%	high
  25% < RHR < 35%	moderate
  RHR < 25%	low

  Low RHR values (< 25%) indicate a significant risk of vascular circulatory disorder.
  The RHR parameter is used to assess dysfunction of the vascular circulation, especially the macrocirculation, and to predict the risk of developing cardiovascular diseases which are often comorbid with diabetes mellitus.