The autonomic nervous system (ANS) is an extensive neural network whose main role is to regulate the internal environment and body functions by controlling homeostasis, hemodynamics, blood pressure, heart rate, blood glucose level, sweating and visceral functions (such as digestion, bladder and sexual organs).
Endothelium vascular function
What is endothelial dysfunction?
The pathological state known as endothelial dysfunction is the earliest clinically detectable stage of cardiovascular disease (which includes heart attacks, stroke, Peripheral Arterial Disease and many other diseases). The functioning of the endothelial cells – endothelial function – is normally kept in balance. Atherosclerosis risk factors such as high cholesterol, high blood sugar, high blood pressure, smoking, aging, obesity, chronic infection, and inflammation, can all disrupt this balance and lead to endothelial dysfunction.
Endothelial dysfunction can be defined as reduced bio-availability of Nitric Oxide (NO), which plays many roles in maintaining vascular health, most importantly its role in vasomotion. Hence, endothelial dysfunction is defined as an impairment of endothelium dependent vasodilatation.
How RM-3-D Body Scanner assess the endothelial dysfunction?
Renua products have been specifically created to enable doctors to efficiently perform this assessment in daily practice with the following improvements*:
1. Use validated procedures (i.e. Contour analysis of the pulse waveform, second derivative analysis, and Pulse wave velocity).
2. Simplified measurement procedures in automatic mode and voice command.
3. User friendly, intuitive software.
4. Improved signal-processing analysis.
5. Quality signal to reduce the time of exam and errors.
6. Use a simple, validated scorecard system, regrouping recognized markers, for fast interpretation of the measured data.
RM-3-D Body Scanner Chart Flow of the endothelial function
*Disclaimer :This test does not replace the conventional diagnosis of cardiovascular diseases and cholesterol.
Galvanic Skin Responses
Renua Medical has a patented new process to test the Sudomotor function using a galvanic skin response (GSR) / sympathetic skin response (SSR) hardware device with interface computer software. (RM 3-D Body Scanner)
Sudomotor function is controlled by
a division of the sympathetic nervous system, which is relating to nerve fibers
controlling the activity of sweat glands (post sympathetic cholinergic fiber or
C-fiber). Sudomotor dysfunction is defined as decreased sudomotor
Traditional neurophysiologic measurements of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions and sympathetic skin response (SSR). The SSR method uses 2 pairs of tactile electrodes that deliver electrical stimulation of the skin and contralateral electrical stimulation of the sweat glands via the sympathetic cholinergic fiber (C-fiber) .
Sudomotor dysfunction has been found as a result of medication side effects, such as cancer treatment, anti-hypertensive treatment (in particular Beta and Alpha blockers, and calcium antagonists), Metformin treatment, vitamin deficiency, etc. Sudomotor dysfunction has also been found as a result of diseases, such as Diabetes, Parkinson's Disease, AISD, Amyotrophic Lateral Sclerosis, Hypothyroidism, kidney and liver diseases, alcoholism, Alzheimer's Disease and Guillain-Barre Syndrome
Studies have shown that assessment of sweat gland innervations through sudomotor function testing can be useful to evaluate neuropathies early.
Flow chart of evolutionary steps of peripheral distal neuropathy. Figure 1
The evolution of peripheral foot neuropathy comprises 4 steps (Figure1)
- Step 1: Microcirculation disorders and decreased skin blood flow
- Step 2: Decreased C-Fiber density
- Step 3: Skin nerve damage (including all the nerves shown in figure 1 and not just the C-Fiber)
- Step 4: Necrosis and amputation decision
Steps 1 and 2 are reversible with effective treatment unlike steps 3 and 4 which only allows for palliative treatment.
An electrical output signal is sent to the skin in contact with the active electrode. Because the voltage is lower than 10 V, it cannot penetrate the stratum corneum; the only way for the current to enter the body is through the eccrine sweat ducts. 1
The signal is carried by the interstitial fluid ions through the body 7 to reach the skin in contact with passive electrode. In the pathway, the signal provokes an electrical stimulation of the post sympathetic cholinergic fiber (C Fiber) 6 which release acetylcholine. 4
Acetylcholine stimulates the nicotinic muscarinic receptors (M receptors). 4
The activation of M receptors will have two effects:
1. Effect on Skin blood flow: Activation of M3 on vascular endothelial cells causes increased synthesis of nitric oxide (NO), which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilatation.
2. Effect on the sweat glands function: Activation of Inositol polyphosphates (IPP's) causes intracellular calcium mobilization and calcium influx. 8 The increased cytoplasmic calcium stimulates chloride channels in the apical (luminal) membrane, and potassium channels in the basolateral membrane of the secretory clear cell of the sweat glands, resulting in the efflux of both ions 8. Chloride enters the secretory cell via either a Na- 2Cl -K or Na - Cl cotransport system, and leaves the cells by diffusion into the lumen of the sweat duct. 7 The movement of chloride across the apical membrane depolarizes the apical membrane and generates a negative luminal potential. This negative lumen charge then attracts sodium into the lumen across the intercellular junction (i.e. paracellular pathway). 9
The two effects of the electrical stimulation process generate electrochemical reactions on the bulk of the passive electrode.
The device generates the reference voltage signal (1.28 V) in DC, that is fed to the active electrode which is connected to the skin of the patient. The signal then passes through the interstitial liquid compartment of the patient and reaches the skin in contact with the passive electrode. The noise is filtered by passing the low frequency filter and then through repeaters providing galvanic isolation, and then the signal processing analysis is performed at the analog-digital converter in digital code. The digital code goes through a galvanic isolation to USB controller and then is released to the slot of the USB port of the computer for the further processing analysis by the software.
Software and new process of measurement
The software receives the digital code of the ADC and display the values in a graphic. Figure 2
Comments figure 2:
During the measurement, the software controls the sequence for each electrode activation and the polarity of the signal (electrical stimulation).
For each pair of electrodes, the
sequence and Polarity are as follow:
Phase 1 the polarity is from cathode to anode during 30 seconds and then in phase 2 the polarity is switched from anode to cathode which generate a peak named peak phase 2
Phase 3 the polarity is from anode to cathode during 30 seconds and then in phase 4 the polarity is switched from cathode to anode which generate a peak named peak phase 4
Time between the switch of polarity
The peak cathode time is immediate, no delay.
The peak anode time is between 1 and 2 seconds: This time is named Latency.
Then, the software converts the ADC digital code in Voltage (mV) and Intensity (mA) according to the ACD manufacturer table. Using the Ohm law formula the software also converts the data in Resistance (KOhm) and then in Conductance (micro Siemens)
In fact, the patented LD technology process is based upon the switch of polarity during the measurement of each pathway between the pair of electrodes and this method has the possibility to separate the 2 effects of the electrical stimulation of the C-Fiber. The Chloride ions cannot discharge in the cathode due to the electronegativity; therefore, we have in the cathode only the effect of the induced vasodilatation (skin blood flow), and in anode the effect of the release of the chloride ions (C-fiber density). I.e. chart flow of the process
Flow chart of the new process to evaluate sudomotor function. Figure 3
Comments Figure 3:
Phase 1: the Current is sent
from cathode E1 to anode E2.
Phase 2: the polarity is switched from anode E2 to cathode E1. The Chloride ions are blocked and the release of NO increases the skin blood flow and a Peak is detected in the graphic: The amplitude of the peak phase 2 reflects the skin blood flow in the skin in contact with the 2 electrodes
Phase 3: the Current is sent from anode E2 to cathode E1
Phase 4: the polarity is switched from cathode E1 to anode E2. The Chloride ions are released and a second Peak is detected in the graphic: The amplitude of the peak phase 4 reflects the C-fiber density in the skin in contact with the 2 electrodes.
Normal Range of the measurement*
Normal Range of the 2 peaks was, evaluated
with a population of 200 people without decreased skin blood flow nor reduced
Peak 2 - Normal range is greater than 900 mV
Peak 4 - Normal range is greater than 1100 mV
Latency - Normal ranger is less than 2 seconds
No differences in the tested
population were found according to gender, weight or height. However,
elderly subjects have a lower voltage (average of 15% lower) compared to
younger aged subjects.
Conditions of the measurement
The subject is measured in the
sitting position and should be relaxed during a period of 5 minutes in order to
avoid sympathetic system activation induced by the standing position.
The temperature should be comfortable ranging from 73 to 75 degrees Fahrenheit in order to avoid activation of the sweat glands from the adrenergic stimulation or vasoconstriction induced by cold plates or extremities.
The electrical stimulation of the nerve induces an action potential, but this action potential will be reduced if the time of stimulation is in excess of 1 minute continuous or if the stimulation is repeated several times. Therefore, successive exams could reduce the peak response and the time between 2 exams cannot be shorter than one hour.
* Once an abnormality is suspected or confirmed, additional evaluation by a physician with specialized tests are recommended.
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