The Method and Apparatus for Peripheral Arterial Disease

Treatment

Alexey Sudarev

1,2

and Evgeny Korotich

1,2

Institute of Radio-Engineering and Electronics RAS, 11 bldg 7, Mokhovaya st., Moscow, 125009, Russia

CONSTEL LLC, 19 bldg. 2 st. Stromynka, Moscow, 107076, Russia

Keywords: Peripheral Arterial Disease (PAD) Treatment, Cardiosynchronized Sequential Antegrade

Pneumocompression (CSAP), Enhanced External Counterpulsation (EECP).

Abstract: The paper is devoted to a new method of peripheral arterial disease (PAD) treatment - cardiosynchronized

antegrade pneumocompression. The method is based on sequential compression of the lower extremities to

create an enhanced antegrade pressure wave in the arteries in order to increase blood flow in the distal parts

of the lower extremities. The main provisions of the method, the physiological model of exposure are

considered. It is shown how to optimally synchronize the impulses with the cardiac cycle for the

simultaneous achievement of a beneficial hemodynamic effect in the limbs and coronary vessels. The

structure of the device for the implementation of the method based on the system for external

counterpulsation CARDIOPULSAR is presented. The physiological effects of exposure (increased blood

flow, ABPI, temperature of the extremities) were investigated. The results of treatment on volunteers were

presented.

https://orcid.org/0000-0001-9683-1922

https://orcid.org/0000-0001-6805-330X

1 INTRODUCTION

Peripheral arterial disease of the lower limb arteries

(PAD) occur in 2 - 3% of the population, accounting

for more than 20% of cardiovascular diseases.

(Dormandy J. et al, Fowkes, F.G.R. et al).

Surgical treatments for PAD are widely used but

non-invasive methods are also known, including

sequential rhythmic pneumatic compression of the

lower extremities using inflatable cuffs (not

synchronized with the heart rate). In particular, the

positive experience of using pneumatic compression

in a peripheral wave mode is known (compression

levels were exceeded the systolic blood pressure on

the brachial artery by 10 - 20 mm Hg) (Lipnitsky

E.M. et al,

Delis K.T., Knaggs A.L.

). In this case the

front duration of pneumatic pulses and the delay

between successive pulses are on the order of

several seconds.

There are also known methods and devices for the

treatment of vascular diseases of the lower extremities

based on compression of the vessels of the affected

extremity with a single cuff synchronized with cardiac

activity (ECG) (Benjamin et al., Dillon RS.).

The widely used Enhanced External

Counterpulsation method (EECP) (Conti C.R) uses

separate cuffs for the shins, hips and buttocks. With

the help of successive compression in the direction

from bottom to top, a retrograde pressure wave is

effectively created in the arterial system, which

increases myocardial perfusion and a simultaneous

release of pressure in the compression cuffs of the

extremities, which reduces the systolic work.

Such an effect is capable of producing a whole

chain of favorable physiological changes in the body

(Bonetti P.O. et al). An increase in coronary blood

flow, in particular perfusion pressure, blood flow

velocity and shear stress in the coronary arteries,

results in the release of vasodilators (NO) and the

release of angiogenesis factors (VEGF). Basically,

the method is used to treat angina pectoris, coronary

heart disease.

This paper describes a method and apparatus for

the treatment of peripheral arterial diseases using

cardiosynchronized pneumatic compression, which

are a development of the previously proposed

methods.

Sudarev, A. and Korotich, E.

The Method and Apparatus for Peripheral Arterial Disease Treatment.

DOI: 10.5220/0010828100003123

In Proceedings of the 15th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2022) - Volume 1: BIODEVICES, pages 58-65

ISBN: 978-989-758-552-4; ISSN: 2184-4305

2 METHOD AND EQUIPMENT

The authors proposed a method of treatment for

PAD - cardiosynchronized sequential antegrade

pneumocompression (CSAP) (Sudarev A.M.,

Sudarev A.M., Korotich E.V.).

In this method, an effective formation of an

antegrade (i.e. towards the distal extremities) wave

is achieved by periodic compression of each affected

limb separately in two zones - proximal and distal.

Compression pulses in the distal zone are delivered

after pulses in the proximal zone with a controlled

delay.

This pressure wave should enhance blood flow

in the distal areas, increases the hydrostatic pressure

and shear stress in the vessels in the areas below the

affected zones, and increases tissue perfusion.

Arterioles and capillaries were chosen as the main

targets of exposure.

To obtain the desired effect, a pressure is created

in the cuffs that exceeds the level of systolic blood

pressure, which leads to the collapse of the arteries

and an intensive redistribution of blood to the

surrounding regions (Bonetti P.O. et al). A pressure

wave arises, propagating in both directions from the

point of occlusion. Compression of the second cuff

located distal to the first leads to an increase in the

pressure wave. In this case, the compression of the

first cuff is a "gate" for the blood pushed out from

the sections of the vessels located under the distal

cuff. The formation of pressure waves is

schematically shown in

Figure 1. This scheme of

action is similar to a peristaltic pump.

Figure 1: Impact mechanism.

For comparison, we present the schemes of

exposure for EECP and CSAP (

Figure 2, Figure 3).

Figure 2: EECP diagram.

Figure 3: CSAP diagram.

In contrast to sequential rhythmic pneumatic

compression, the external pressure slew rate value is

fundamentally important, because the change in

microcirculation in the distal regions, especially in

the terminal arteries, arterioles and capillaries,

depends on the compression slew rate in the

proximal region. As shown in (Conti C.R et al,

Bonetti P.O. et al), with a decrease in the pressure

pulse leading edge duration, the maximum attainable

pressure in the outer regions increases. Accordingly,

an increase in arterial pressure leads to an increase in

capillary blood flow. With a slow slew rate, the

pressure wave outside the compression zone is

shunted by the collaterals and does not reach its

maximum possible magnitude.

It was proposed to synchronize the compression

pulses with the cardiac cycle in order to ensure the

optimal superposition of the native pulse wave with

the wave created by pneumatic compression for the

most effective increase in perfusion pressure, and,

accordingly, blood flow in the distal regions.

As will be shown below, this synchronization

may be beneficial for two reasons: it increases the

blood flow in the extremities, and it increases the

blood flow in the myocardium with a simultaneous

decrease in the systolic work. At EECP usage only

the second goal is usually achieved.

The Method and Apparatus for Peripheral Arterial Disease Treatment

For the maximum amplification of the wave

propagating in the antegrade direction, the moment

of the beginning of limb compression was proposed

to be synchronized with the propagation of the

natural pulse wave maximum through the

compression zone. In this case, the superposition of

these two waves is maximum. This moment

corresponds to the ejection phase at the orifice of the

aorta plus a delay in the propagation of the pulse

wave from the orifice of the aorta to the site of cuff

application. The delay of the impulse in the distal

cuff relative to the proximal one should be of the

order of the time of propagation of the pulse wave

between the cuffs.

The timing diagram of the exposure is shown in

the

Figure 4.

Figure 4: CSAP timing diagram.

Therefore, to maximize the antegrade wave, the

time of the onset of the pulse in the proximal cuff is

estimated as follows: t

prox

= t

+ t

pr1

, where t

is the

moment in the interval from the beginning of the

ejection phase to the moment of the systolic

maximum pressure t

smax

at the aortic orifice, and t

pr1

is the time of propagation of the pulse wave from the

aortic orifice to the site of the proximal cuff. More

accurate determination of t

prox

could be made

experimentally.

On average, t

smax

(systolic maximum) is

separated from the R-peak of the ECG by a time of

the order of 0.15 ÷ 0.2 sec.

In this case, t

pr1

= L

/ v, where v is the speed of

the pulse wave in large arteries (4–7 m/sec (Caro

C.G. et al)), and L

is the distance from the aortic

orifice to the site of the proximal cuff. When the cuff

is applied to the hip, t

pr1

is about 0.05 ÷ 0.1 sec. This

gives t

prox

(delay in the onset of compression in the

hip cuff relative to the R-peak of the ECG) of the

order of 0.2 - 0.3 sec.

The delay between pressure pulses in the

proximal and distal cuffs is t

pr2

= L

/ v, where L

the distance between the cuffs, which for t

pr2

gives

about 0.03 ÷ 0.06 sec.

When the vessels are compressed by the

proximal cuff, a retrograde pressure wave is also

formed, propagating towards the aorta. To increase

coronary blood flow in this case (similar to the case

of external counterpulsation) it is necessary that it

reaches the aortic orifice during diastole. Thus, the

lower limit for the beginning of the pressure in the

proximal cuff is as follows: t

prox

≥ t

-t

pr1

, where t

the end of the ejection phase (the aortic valve

closure time is about 0.3 sec, approximately

corresponding to the end of the T-peak of the ECG

(Caro C. G. et al)), which gives the limit for t

prox

not less than 0.15 ÷ 0.25 sec.

The inflation of the cuffs should be carried out

simultaneously before the onset of mechanical

systole in order to ensure a decrease in the

mechanical work of the heart, similar to the method

of EECP (Conti C.R et al).

The described method of exposure was

implemented on the basis of the system for external

counterpulsation CARDIOPULSAR™ (CONSTEL

LLC, Russia) (www.constel.ru).

The general scheme of the device in the

antegrade pneumocompression mode is shown in

Figure 5. The hip and shin cuffs are used as

proximal and distal cuffs, respectively. To

synchronize the pressure pulses in the cuffs, an

electrocardiogram (ECG) signal was used. Pressure

pulses in the cuffs, are given taking into account the

delay of the incoming pulse wave in relation to the

R-peaks of the ECG. To create the necessary time

diagram of the compression effect on the lower

extremities the software of the CARDIOPULSAR™

system was modified. A photoplethysmogram sensor

placed on the toe was used to monitor changes in

blood flow. This sensor can also be used to optimize

the exposure timing.

BIODEVICES 2022 - 15th International Conference on Biomedical Electronics and Devices

An experimental study of the physiological

effect of our proposed new method of

pneumocompression (CSAP) was carried out.

Figure 5: Device diagram.

3 EXPERIMENTAL STUDY AND

RESULTS

To study the effect of the cardiosynchronized

compression on the circulatory system of the

extremities in practically healthy people and patients

with PAD an experimental study was carried out to

assess the change in blood flow in a toe.

The experimental studies involved volunteers: 4

apparently healthy adult men aged 22 to 50 years

and 10 patients with atherosclerosis of the lower

extremities, chronic vascular insufficiency of groups

2A and 2B aged 45 to 65 years.

Each episode included a standard 60 minute

session.

The graphs (Figure 6 and Figure 7) show typical

physiological signals without compression impact

(Figure 6) and with impact (Figure 7): ECG signal,

cuff pressure plots (hip and shin) and a

photoplethysmograph signal (PPG) reflecting the

pulse blood filling in the toe.

The difference between ECG signals (Figure 6

and Figure 7) is due to mechanical artifacts during

periodic compression.

It can be seen that during the application of the

compression, an increase in the pulse wave occurs.

The characteristic increase in the PPG amplitude

compared to the initial level is 2 to 4 times.

Figure 6: ECG, cuff pressure and PPG before exposure.

Figure 7: ECG, cuff pressure and PPG during exposure.

We studied the influence of the amplitude-time

parameters of pneumatic pulses on the

hemodynamic effects. Particularly the dependences

of the increase in blood flow in the distal part of the

limb (PPG amplitude on the toe) vs the amplitude of

the compression pulses and their delay relative to the

R-peak of the ECG, were investigated.

The dependence of the PPG amplitude on

compression pressure was measured by a sequential

increase in the amplitude of the compression pulses

with a step of 10 mm Hg approximately every 20

sec. Typical dependences (on 4 subjects coded as

S1, S2, S3, S4) in an experiments with a normal

level of systolic pressure (<140 mm Hg) of the PPG

amplitude vs compression pressure are shown on

Figure 8 (solid lines show the interpolation of trends

by fourth-order polynomials).

The Method and Apparatus for Peripheral Arterial Disease Treatment

It can be seen that the dependences have a

characteristic S-shape. The beginning of the growth

of the PPG amplitude begins at compression

pressures of 100-120 mm Hg. The maximum values

are reached at pressures of 150-250 mm Hg, which

corresponds to systolic blood pressure. These results

indicate that the maximum effect is achieved with

collapse of the arteries under the cuffs.

Figure 8: PPG amplitude on the toe vs cuffs pressure.

The amplitude of pneumatic pulses required to

maximize blood flow in the distal regions are

slightly more than systolic blood pressure. It could

be explained by the fact that the actual mechanical

stress of the underlying tissues is slightly less than

the pressure in the inflatable chambers. The

difference therefore depends on the type of

compression cuffs (their geometric and design

features).

The dependence of the shape and the resulting

amplitude of the pulse wave on the delay in the

onset of the pressure pulse in the proximal cuff was

studied. The characteristic shape of the PPG signal

at different delays looks is shown in Figure 9.

Figure 9: 1 - No action, 2 - long delay, 3 - optimal delay.

The dependence of the PPG amplitude on the toe

on the delay between the R-peak of the ECG and the

onset of compression in the femoral cuff was

investigated experimentally. A typical dependence

of the averaged PPG amplitude over approximately

20 cardiac cycles is shown in Figure 10. On the

graph, the ordinate shows the delay between the R-

peak and the moment when the pressure in the cuff

has reached the amplitude value. In this case, the

delay between the onset of impulses in the hip and

shin cuffs was constant (40 msec). It should be noted

that the reported values of the delay may have an

error of the order associated with the inaccuracy of

the formation of pressure pulses (10–20 msec)

relative to the R-peak, as well as with the duration of

the pulse front (approximately 70–90 msec).

Figure 10: Dependence of the PPG amplitude on the delay

between the R-peak and the moment of reaching the

nominal pressure in the pulse in the hip cuff.

The graph repeats the characteristic shape of

PPG (maximum (plateau) at low values and a

smooth decline with increasing delay). This

dependence characterizes the superposition of two

waves in the distal regions: a natural pulse wave and

a wave caused by compression (similar to the effects

observed with external counterpulsation).

As a result, the shape and amplitude of the

photoplethysmogram in the distal parts of the limb

may be used as a feedback signal for more accurate

adjustment of the exposure time diagram (Sudarev

A.M., Korotich E.V.), since the time of occurrence

and the degree of actual compression of the tissues

of the extremities by the cuffs depends on often

uncontrollable factors: the delay in the measuring

and acting tract, the design and degree of the initial

tightening of the compression cuffs, the speed of

propagation of the pulse wave, etc.

To achieve the maximum effect it is necessary to

adjust the delay and the magnitude of the pneumatic

impulse pressure achieving the maximum PPG

amplitude and the approach of the moment of the

maximum of the amplified blood flow wave to the

systolic maximum of the natural wave. It should be

BIODEVICES 2022 - 15th International Conference on Biomedical Electronics and Devices

noted that the decrease in latency should be limited,

since the resulting retrograde wave should reach the

aortic orifice in the diastolic phase. An excess value

of the compression pressure leads to unwanted

trauma to the underlying tissues without leading to

an effect increase. This is evidenced by the

saturation of the dependence of the increase in blood

flow when the compression pressure is exceeded by

more than 50-70 mm Hg above the systolic pressure

levels (Figure 8).

To compare the hemodynamic effect in the distal

parts of the limb in the CSAP and EECP modes,

experiments were carried out in which the change in

the PPG amplitude on the toe in these modes relative

to the background level was compared. The gain was

measured as K

ampl

= PPG

exp

/ PPG

back

, where PPG

exp

is the amplitude of PPG during exposure, and

PPG

back

is the amplitude of PPG without exposure.

In healthy volunteers (5 test subjects, 2 experiments

carried out at different times), K

ampl

in the CSAP

mode was 1.8 ± 0.3 times higher than in the EECP

mode.

Subsequently data on the greater efficiency of

enhancing blood flow in the distal regions in the

CSAP mode compared to EECP were repeatedly

confirmed (in more than 100 patients with PAD) in

clinical studies (Atkov O. U. et al).

It is known that the distal parts of patients with

PAD are often colder due to circulatory

insufficiency. To investigate changes in limb

circulation in two patients with PAD, a study was

carried out using a thermal imager (IRTIS-2000,

Russia).

The surface temperature of the skin, especially

the limbs, measured by the thermal imager varies

greatly depending on many factors. The

experimental conditions (external temperature and

long-term adaptation to the lying position) were

selected in such a way as to minimize the natural

temperature drift as much as possible.

The results of a typical experiment are shown in

Figure 11and Figure 12.

The temperature of the toes increases markedly

10-30 minutes after the start of the procedure (up to

1-2 ° C). In addition, preliminary data show that the

temperature of the feet increases after a course of

procedures. An increase in foot temperature

indicates an integral increase in blood circulation.

In the initial period of the study of the

effectiveness of the treatment, a series of procedures

was carried out in volunteer patients with PAD

(diagnosis: atherosclerosis of the lower extremities,

chronic vascular insufficiency, stages 2A and 2B by

Fountaine), which made it possible to assess the

change in the course of the disease and draw a

conclusion about the clinical effect. The studies

involved 10 patients. Each patient underwent 12 to

15 procedures, 60 minutes each.

Figure 11: Thermal image before exposure.

Figure 12: Thermal image (30 min after start of exposure).

The Method and Apparatus for Peripheral Arterial Disease Treatment

All patients showed an increase in exercise

tolerance (6-minute walk test until the onset of

discomfort and pain in the shin muscles). The

increase in distance was from 22 to 100% after the

first two procedures.

The measurements of the ankle-brachial index

(ABI) were also carried out, calculated as the ratio

of arterial systolic pressure in the distal parts of the

legs to systolic pressure in the brachial arteries.

After a cycle of procedures in each of the patients,

the index increased by 0.1 ± 0.05 with the initial

values from 0.7 to 0.8.

In all patients with disease stages 2A and 2B,

after the first procedure, subjective improvement

was noted: discomfort in the limb, a feeling of

coldness, especially in the distal parts, a feeling of

cold in the legs, the need to keep the distal part of

the limb warm during sleep, etc.

After receiving the first positive results, a

multiclinic study of the effectiveness of the proposed

therapeutic method was carried out on a large group

of patients with multifocal atherosclerosis (Atkov O.

U. et al). This study showed that the use of the

method and the CARDIOPULSAR device leads to

an increase of pain-free walking distance, an

increase of ankle-brachial pressure index (ABPI),

and an improvement of microcirculation. The

improvement of life quality estimated by DASI

Activity Index and Edinburgh Claudication

Questionnaire (ECQ) was also shown.

4 CONCLUSIONS

The method and device of pneumatic compression

effect on blood circulation of the extremities for the

treatment of PAD achieving an effective increase in

blood flow in the distal regions have been developed.

The primary hemodynamic effects of exposure

and the dependence of an increase of blood flow in

the distal regions on the amplitude-time

characteristics of pneumatic pulses were studied.

The results of clinical application of the method

on volunteer patients suffering from PAD

(obliterating atherosclerosis, endarteritis, diabetic

angiopathy) have been obtained, which indicates its

promising potential.

ACKNOWLEDGEMENTS

We would like to thank the following people who

have helped us undertake this research:

Prof. Gennady G. Amosov (R.I.P.) for inspiring us

initial ideas and cooperation,

The CONSTEL LLC staff that helped us in any

aspects and especially Oleg Uss and Lev Mershin

for help in preparation of the text.

REFERENCES

Atkov O. U., Zudin A. M., Shugushev Z. H ., Orlova M.

A., Sudarev A. M., Korotich E. V., Maximkin D . A.,

Patrikeev A. V. (2015) Short-term results of

cardiosynchronized consequential antegrade

pneumocompression in patients with multifocal

atherosclerosis Rossijskij kardiologicheskij zhurnal

(Russian Journal of Cardiology), 3 (119): 82–88

Benjamin et al. (1978) Apparatus for promoting blood

circulation. Pat. US 4077402

Bonetti P.O., Holmes D.R., Lerman A., Barsness G.W.

(2003) Enhanced external counterpulsation for

ischemic heart disease - What's behind the curtain?

Journal of the American College of Cardiology.; 41:

11: 1918-1925

Caro, C. G., Pedley, T. J., Schroter, R. C. and Seed, W. A.

(1978) The Mechanics of the Circulation, Oxford

University Press. (527 pp.)

Conti C.R., (1999) EECP-Enhanced External

Counterpulsation, Journal of the American College of

Cardiology.; 33: 7: 1841-1842

Delis K.T., Knaggs A.L. (2005) Duration and amplitude

decay of acute arterial leg inflow enhancement with

intermittent pneumatic leg compression: an insight

into the implicated physiologic mechanisms. J Vasc

Surg.; 42(4): 717-25.

Dillon R.S. (1997) Fifteen years of experience in treating

2,177 episodes of foot and leg lesions with the

circulator boot. Angiology.; 48: 17-34

Dillon R.S. (1996) Method for promoting circulation of

blood. Pat US 5514079

Dormandy, J & Mahir, M & Ascady, G & Balsano, F & de

Leeuw, Peter & Blombery, Peter & Bousser, M &

Clément, Daboné & Coffman, J & Deutshinoff, A.

(1989). Fate of the patient with chronic leg ischaemia.

A review article. The Journal of cardiovascular

surgery. 30. 50-7

Fowkes, F.G.R. & Housley, E & Cawood, E.H.H. &

Macintyre, Colin & Ruckley, C.V. & Prescott, Robin.

(1991). Edinburgh Artery Study: Prevalence of

Asymptomatic and Symptomatic Peripheral Arterial

Disease in the General Population. International

journal of epidemiology. 20. 384-92.

Lipnitsky E.M., Amosov G.G., Morozov K.M., Zateryukin

A.B., Platonov A.Yu., Vaidya A. (2007) Rhythmic

pneumocompression for treatment of patients with

chronic obliterating diseases of the lower-limb arteries

Angiologiya i sosudistaya hirurgiya (Angiology and

vascular surgery). 13: 3: 22-26 (in Russ.)

Sudarev A.M. (2013) Treatment for chronic obliterating

diseases of lower limb arteries. Angiologiya i

BIODEVICES 2022 - 15th International Conference on Biomedical Electronics and Devices

sosudistaya hirurgiya (Angiology and vascular

surgery) 19, 1 . 26 -32 (in Russ.)

Sudarev A.M., Borodyanskaya E.S., D'yachenko A.I.

(2010) Modeling of external counterpulsation

gemodynamic effects by means of electrical analogs.

III Evrazijskij kongress po medicinskoj fizike i

inzhenerii "Medicinskaya fizika - 2010"; 4: 106-108

(in Russ.)

Sudarev A.M., Korotich E.V. (2016) Method and devices

providing impact on cardiovascular system. Pat. US

US2013102939

The Method and Apparatus for Peripheral Arterial Disease Treatment