The Autonomic Vascular Signal (VAS) that was discovered by Paul Nogier in 1965 is a cornerstone of the auricular medicine.

There is no doubt, that VAS is an outstanding discovery of the 20th century and if documented and standardized, could change our knowledge both in vascular biology and physiology, as well as in medical practice. Nevertheless, a third of a century has passed, but VAS has not yet been assessed and standardized by FDA-approved technology. There is a paradox:

VAS is an outstanding discovery that is easily palpable, but can not be properly objectivated.

WHAT IS THE REASON?

Historically, as outlined by Thomas Kuhn in his book "The structure of scientific revolutions" (1), every discovery could be accepted only after it successfully overcome three periods in its development. When the fact of the discovery is recognized (the 1st period), it is necessary for its future development to refine its concepts and construct elaborate equipment. This second period is the most crutial in the development of the discovery. And in the last, third period, the discovery is usually integrated into "normal science" as a part of this science.

In my opinion, as far as VAS-phenomenon is concerned, now we are at the end of the second period (refinement of concepts and constructing of equipment) and on the threshold of the third period (integration of the discovery into academic medicine).

The research of the second period of VAS development was carried out mainly by Dr. Navach from 1977 through 1985 and continued by Dr. Ackerman (2, 3, 4, 5, 6). It has been documented that VAS is indeed a valid phenomenon that can be objectivated. Moreover, Navach proposed new concepts of the VAS-phenomenon and developed a computerized device to record VAS in clinical conditions.

VAS features defined by Navach are presented in Table 1.

Table 1. VAS-phenomenon features defined by Navach

* VAS is a measurable manifestation of a vascular autonomic information transfer system.

* The smooth muscle of peripheral arteries is responsive to this biophysical system.

* VAS is primarily related to peripheral vascular tone.

* VAS occurs in every artery of the body.

* Blood flow in arteries is of a spiral helix form.

* The positive and negative VAS phenomenona are merely representative of the rotational positions of the helix.

* When a positive VAS occurs, the area underneath the pulse wave after the dicrotic notch increases, and when a negative VAS occurs the area after dicrotic notch decreases.

It must be emphasized that the recent revolutionary discoveries that have changed our knowledge in vascular physiology only confirm and detal these Navach's concepts.

Thus, not long ago it was discovered that blood flow in muscular arteries is indeed a spiral laminar flow. Till now this fact has not been fully accepted by classical vascular physiology (7).

Nevertheless, the main discovery that has changed our knowledge in vascular biology and physiology, is the revealing of the biological role of endothelium (8) and nitric oxide (NO) (9). This discovery is very important for understanding VAS-phenomenon, and may change the classical concepts of this phenomenon.

In the last 10 years there has been accumulatingevidence that vascular endothelium is a complex and active organ with varied and broad ranging fuctions (10).

The endothelial cells provide an interface with the bloodstream, sensing (1) changes in flow, (2) pressure, (3) inflammatory signals, and (4) levels of circulating hormones. The effector organ is the vascular smooth muscle cells that modulate vascular tone. The endothelium controls vascular smooth muscle tone by secreting substances that cause relaxation and contraction. Under physiological conditions the endothelium constantly releases NO, a process regulated by the effect of shear stress on endothelial cells. NO acts directly on vascular smooth muscles, coordinating and fine-tuning the whole cardiovascular system (CVS).

Today it is established that NO plays a crucial role in regulating blood pressure, in controlling anxiety and regulating circadian rhythms. It also must be outlined that NO act as a neurotransmitter, helping brain cells to communicate with one another.

Indeed, before long it became difficult to name an important physiological process in which NO was not involved. In 1992 the journal "Science" proclaimed NO "Molecule of the Year" (11), and in 1998 the principal discoverers and researchers of NO biological action were rewarded the Noble Prize. One can see the modern data on blood vessel functions in Table 2.

Table 2. Blood vessel functions: modern data supporting VAS-phenomenon

* Vasculature is a vital organ that can regulate its own tone and structure.

* Blood vessels are a dynamic organ that is capable of

(1) sensing changes in its surroundings,

(2) communicating such changes, and

(3) subsequently altering its structure.

* Blood vessel functions are modulated by

(1) vasoactive substances, and

(2) hemodynamic stimuli.

From the standpoint of VAS theory, one should emphasize the exclusive role of the mechanical stimuli in fast (during few pulse beats) adaptation of the vascular system (12, 13, 14, 15).

The adaptive capability of vascular system depends on mechanical stimuli:

- wall shear stress and

- transmural pressure.

Flow-related wall shear stress influences:

- smooth muscle tone,

- the arterial lumen changes,

- adaptive regulation of blood flow;

- optimizing the vascular tree function.

Flow-related dilation is endothelium-dependent and mediated by NO. One relaxes vascular smooth muscle cells and acts as a vasodilator in large arteries. Also it increases distensibility; decreases pulse wave velocity, slows returning the reflected pressure waves, decreases afterload coordinates and fine-tunes the whole CVS.

Release of NO is modulated by (1) wall shear stress, (2) frequency of pulsatile flow, and (3) amplitude of pulsatile flow.

These novel data affirm that

1. Vascular system is a self-organizing system that coordinates and fine-tunes all its parts in a single fast response system playing regulatory roles in adaptation of the living organism.

2. Vascular system is autoregulated by wall shear stress and smooth muscle tone interactions by NO mechanisms. NO is the main "hormone" of vascular regulation. NO release is modulated by wall shear stress and it acts directly on vascular smooth muscle cell regulating both vascular tone and wall shear stress.

Thus, the main Navach's conception that VAS is a vascular autonomic system which is manifested by changes in vascular tone of peripheral arteries is confirmed by the newest academic research.

On the other hand, some former classic concepts of the VAS-phenomenon mechanisms are contradicted with this new research data and must be refined.

Firstly, it must be emphasized, that vascular tone is autoregulated by flow-related wall shear stress through NO-pathway. The classic conception that VAS acts only through sympathetic outflow mechanism, is not correct.

Secondly, the modern hemodynamic research does not confirm the classic "standing wave" theory.

Today the mechanisms of pulsatile blood flow and blood pressure patterns have been investigated from the standpoint of spiral waves formation, soliton waves theory, etc. This question is argumented more detail in my and Dr. Dvorkin's publication in Coherence 2/98 (16).

Besides, there are some more reasons for VAS-paradox. One reason is the fact, that modern FDA-approved technique still can not provide a precise measurement of beat to beat fluctuations in vascular tone.

And the last but not the least reason is the methodological approach to identification of VAS. The " manual" VAS, as a subjective method, could not be accepted as a "gold standard" for VAS evaluation through, in our opinion, the "manual VAS" also could be explained by changes in vascular tone.

In my opinion, new ways for VAS-objectivation must be grounded only on the concepts of VAS confirmed by modern academic research data. In Table 3 are summarized these concepts.

Table 3. Modern concepts of VAS

1. Vascular autonomic system exists as a specific biophysical informative system.

2. Theoretically, the vascular system could be assumed as an extremely precise analog system, represented by (1) shear stress, (2) direction of flow, (3) wavelength variations.

3. VAS occurs in every artery of the body and is expressed by changes in vascular tone and variations in blood flow.

4. The vascular tone can be tune-autoregulated by mechanical stimuli and by their interaction with sympathetic outflow to vascular smooth muscle cells, regulating both vascular tone and shear stress.

5. Theoretically, it is possible to register VAS in different parts of the vascular system as beat-to-beat changes of arterial smooth muscle tone.

Methods of beat-to-beat pulse waveform changes measurement

It is known that signal strength related parameters such as area under the curve, amplitude and the flux reflect changes in vascular tone.

I will not discuss methods used formerly to objectivate VAS. None of these methods can be considered a standard clinical method for VAS-objectivation.

The author's view of the VAS objectivation

Since VAS occurs in every artery of the body, the measurement of the typical for VAS changes in blood flow in a body region, may be highly informative for VAS assessment. In a separate artery, the local changes in vascular tone are conditioned by many individual anatomical and physiological factors that vary from individual to individual. Investigations of the summarized effect of VAS specific changes in different regions could be provided correctly by electroimpedance plethysmography (EIP) methods (17, 18, 19). Table 4 presents main reasons for using EIP to objectivate VAS.

Table 4. The reasons for using EIP by VAS-recording

* There is a perfect theoretical relationship between electrical and hydrodynamic (hemodynamic) laws.

* The measurement of electrical parameters can be extremely accurate.

* There is a very good correlation between variation in electrical parameters and the corresponding variation of the cross-sectional areas of the lumen of participating blood vessels.

* EIP measurements can be done in real time continuously.

* EIP measurements may be fully computerized.

* EIP measurements are totally harmless.

Dr. Dvorkin and I investigated the possibilities of a new FDA-approved bioimpedance device for objectivation VAS. The comparison was made with "manual" VAS provided by Dr. Dvorkin. The results are good. There is no time to discuss these results now. The Figures 1 and 2 represent a typical example of VAS in a patient with hypertension during VAS investigation. A stimulattion on the thalamic point with a pressure detector changes the thypical negative VAS (Fig. 1) to a typical positive VAS (Fig. 2).

It seems that electroimpedance plethysmography may be a method of choice for objective measuring VAS and for developing clinically useful automated, computerized, cost-effective devices for recording the VAS-phenomenon.

Fig. 1. Negative VAS: in diastolic parts of the curves the additional waves are absent.

Fig. 2. Positive VAS: there are additional stable waves in the late diastole.

CONCLUSION

1. The circulatory system constitutes the principal coordinating and integrating system of the body.

2. The CVS is controlled by endothelium-derived factors, mainly NO that acts directly on the vascular smooth muscle cells, coordinates and fine-tunes the whole CVS.

3. Release of NO is modulated both by the frequency of pulsatile flow, and the amplitude of pulsatile flow.

4. Theoretically, the vascular system could be viewed as an analog system, represented by the strength of flow (shear stress), direction of flow, slow wavelength variations in its strength.

5. VAS as a phenomenon is expressed by fast (beat-to-beat) changes of arterial smooth muscle tone.

6. Assessment of beat-to-beat changes in vascular tone may be provided by "manual" VAS and by new methods for measurement of beat-to-beat changes in pressure and flow pulse wave contour, and/or pulse wave velocity.

7. Electroimpedance plethysmography seems to be a method of choice for objective measuring VAS and developing clinically useful automated, computerized, cost-effective devices to document of the VAS-phenomenon.

REFERENCES

1. Kuhn T. The structure of scientific revolutions. Second Edition, The University Chicago Press, London, 1970.

2. Navach JH. The vascular autonomic system, physics and physiology. The YII German-Latino Congress on Auricular Medicine, September 11, 1981, Lyon, France.

3. Navach JH. The vascular autonomic system pulse, recording techniques. First International Congress of Acupuncture and Auricular Medicine, September 19, 1980, Mallorca, Spain.

4. Navach JH. Measuring the physiological functions comprising the vascular autonomic system. The VII German-Latino Congress on Auricular Medicine, September 10, 1981, Lyon, France.

5. Ackerman JM. The biophysics and neurochemistry of the VAS- its' relationship to healing (part one). Coherence 1998; 2: 5-22.

6. Ackerman JM. The biophysics and neurochemistry of the VAS- its' relationship to healing (part two). Coherence 1999; 1: 5-10.

7. Stonebridge PA, Brophy CM. Spiral laminar flow in arteries? Lancet 1991; 338(8779): 1360-1.

8. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of the arterial smooth muscle by acetylcholine. Nature 1980; 286: 373-76.

9. Ignarro LJ. Biosynthesis and metabolism of endothelium-derived nitric oxide. Ann Rev Pharmacol Toxicol 1990; 30: 535-60.

10. Luscher TF, Vanhoutte PM. The endothelium: modulator of cardiovascular function. Boca Raton, Fla, CRC Press Inc, 1990, pp 1-228.

11. Lane NJ. Blood ties. The Sciences, 1998; September/October: 24-28.

12. Henderson AH. Endothelium, for example. J Royal Col Physicians of London 1996; 30: 42-51.

13. Gibbons GH. Endothelial function as a determinant of vascular function and structure: a new therapeutic target. Am J Cardiol 1997; 79(5A): 3-8.

14. Luscher T, Rubanyi G (Ed). Endothelium as a regulator of vascular tone and growth. Circulation 1993; 87 (Suppl): V1-V85

15. Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev 1995; 75: 519-60.

16. Frinerman E, Dvorkin E. Vascular autonomic signal: perspectives of computerized machinery registration. Reported at the 2nd Annual Conference of MSAIMA, November 24, 1994, Tel-Aviv, Israel, IJMA 1995; 1: 21-22.

17. Frinerman E, Dvorkin E. Hemodynamic changes during puncture of beta-1-blocker analogue auricular point. IJAM 1995; 1: 40-43.

18. Frinerman E, Dvorkin E. Letters to the editor. IJAM 1996; 2: 34-37.

19. Frinerman E, Dvorkin E. Is an "angiometric test" an adequate test for registering the vascular autonomic signal? Coherence 1998; 2: 41-44.

20. Zhukovskii LI, Frinerman EA. Physical and physiological grounding of clinical rheography. In: Clinical rheography. Shershnev, ed. Zdorov'ia, Kiev, 1976, p 8-13.

21. Frinerman E, Klinger I, Kishon Y. Stroke volume distribution between lower and upper parts of the body in patients with atherosclerosis and health persons. Isr J Med Sci 1996; 32(10): 1022.

22. Cohen A, Frinerman E, Katz M, Ezra S, Dotan A, Weissberg M, Schachner A. Validity of bioimpednce hemodynamic measurements during coronary artery bypass grafting. Cardiovasc Diagn & Proceed 1996; 13(1): 57.