experimental study of the effect of external ... · that ecp could be an effective treatment for...

Clin Invest Med • Vol 23, no 4, August 2000 239

Abstract

A bidirectional ultrasonic Doppler flowmeter with directsingle sideband separation was used to measure bloodflow in the femoral and dorsalis pedis arteries of 18 nor-mal volunteers. Changes in blood-flow velocity and vol-ume during external counterpulsation (ECP) with varioussustaining times (the time for maintaining pressure) forinflation were studied. The results showed that blood-flow velocity in the femoral and dorsalis pedis arteries isincreased significantly by ECP, but the change is notclosely related to the duration of inflation. For a shortsustaining time, the net forward blood-flow volume inarteries increased remarkably, but at longer sustainingtimes it dropped back significantly to a value even lowerthan that before ECP. The sustaining time for inflation toproduce the maximum net forward flow volume (theoptimal sustaining time of inflation) was found to be atone-quarter to one-third of the cardiac cycle. In a secondstudy, changes in the calibre of the femoral artery and itscollateral and anastomotic branches in the hind extremi-ties in 5 dogs before and after ECP with an optimal sus-taining time of inflation were examined by femoral arte-riography. The experiments showed that the patency ofcollateral and anastomotic branches of the femoral arterywas greater before than after ECP. The study suggeststhat ECP could be an effective treatment for improvingthe blood circulation in extremities.

Résumé

On a utilisé un débitmètre Doppler bidirectionnel à ultra-sons avec séparation directe à bande latérale unique pourmesurer le débit sanguin dans les artères fémorale et dor-sale du pied de 18 volontaires normaux. On a étudié leschangements de la vélocité et du volume du débit sanguinau cours d’une contrepulsion externe (CPE) compte tenude diverses périodes de maintien (de la pression) pourl’inflation. Les résultats ont montré que la CPE augmenteconsidérablement la vélocité du débit sanguin dans lesartères fémorale et dorsale du pied, mais que le change-ment n’est pas lié étroitement à la durée de l’inflation.Pendant une période de maintien brève, le volume net duflux sanguin à la pression dans les artères a augmenté defaçon remarquable, mais lorsque les périodes de maintiense sont allongées, il est retombé considérablement, mêmeau-dessous de la valeur antérieure à la CPE. On a con-staté que la période de maintien de l’inflation nécessairepour produire le volume net maximal du flux à la pres-sion (la durée optimale de maintien de l’inflation) sesituait encore vers le quart ou le tiers du cycle cardiaque.Au cours d’une deuxième étude, on a étudié par arté-riographie fémorale les changements du calibre del’artère fémorale et des artères collatérale et anastomo-tique des membres arrière de cinq chiens avant et aprèsCPE avec une durée d’inflation soutenue optimale. Lesexpériences ont montré que la patence des artères col-latérale et anastomotique de l’artère fémorale était plusgrande avant la CPE qu’après. L’étude indique que laCPE pourrait être un traitement efficace pour améliorer lacirculation sanguine dans les membres.

Dawei Cai, Ruiliang Wu, Ying Shao

(Original manuscript submitted Oct. 14, 1999; received inrevised form June 19, 2000; accepted July 5, 2000)

Clin Invest Med 2000;23(4):239-247.

© 2000 Canadian Medical Association

Medical subject headings: blood circulation; blood flow veloc-ity; blood volume determination; counterpulsation; femoralartery; tibial arteries

Drs. Cai, Wu and Shao are with the ExternalCounterpulsation Laboratory, Clinical Medical College,Shanghai Medical University, Shanghai, China

ORIGINAL ARTICLE

Experimental study of the effect of externalcounterpulsation on blood circulation in the lowerextremities

Table of ContentsReturn to August 2000

http://www.cma.ca/cim/vol-23/issue-4/issue-4.htm

Introduction

External counterpulsation (ECP) is a new noninva-sive technique used in the treatment of variousischemic diseases. By using the “R” wave of the elec-trocardiographic (ECG) signal as a trigger, the cuffswrapped around the extremities and buttocks areinflated at diastole and apply pressure to the arteriesof the extremities. This causes the diastolic pressurein the aorta to rise due to the blood flowing back intothe aorta from the arteries of extremities. Therefore,the perfusion pressure of the coronary and the com-mon carotid arteries increases and blood flow to theheart and brain is increased, as shown in animal andclinical studies.1–3 This technique has also been usedin clinical trials for the treatment of coronary andcerebrovascular insufficiency and appears to be ofbenefit.4,5

As part of the blood flows out of the extremitiesand returns to the aorta at diastole and the extrem-ities are temporarily ischemic, some symptomsmay occur during ECP therapy. Some patientscomplain of numbness of their extremities whenthe sustaining time for inflation or the treatmenttime is long.

It is not presently known how the blood-flowvelocity and the blood volume in the arteries of theextremities change during ECP, whether ECP iscapable of augmenting the blood supply to theextremities or what are the indications for ECP ther-apy for ischemic extremities and for ischemicextremities associated with coronary or cerebrovas-cular insufficiency.

This report describes experimental observations inhuman volunteers and animals of the change inblood-flow velocity and blood volume in peripheralarteries during ECP and the changes in collateral cir-culation after ECP.

Materials and methods

According to hemodynamics, the flow volumethrough a blood vessel given by thePoiseuille–Hagen equation7 in the absence of turbu-

lence is as follows:

Since the maximum flow velocity is:

the equation for flow volume can also be written as:where flow volume (Q) is proportional to the 4thpower of the radius of the vessel (R4), the maximumflow velocity (Umax) is proportional to the square ofthe radius of the vessel (R2) and both of them are indirect proportion to the pressure difference (∆P)between the 2 ends of the vessel. However, they arealso inversely proportional to the viscosity of blood(η) and the length of the vessel (L). If the radius of

the vessel remains unchanged, the flowv o l u m e

is proportional to the flow velocity (Umax)

and the time duration (t). For a constant flow veloci-ty, the longer the time, the larger is the blood volume.In order to increase the flow velocity and flow vol-ume in the peripheral vessels, different pressure dif-ferences between the 2 ends of the vessel and thetime duration of the blood flow have been investigat-ed to determine empirically the optimum conditions.

Human studies

Eighteen healthy volunteers, (16 men, 2 women,mean [and SD], age 35.5 [2.3] years, ranging from 27to 62 years) without peripheral vascular disease werestudied. Blood-flow velocity was detected using abidirectional ultrasonic Doppler flowmeter with directsingle sideband separation (Model F-1, ElectronicEngineering Department, Fudan University, China6).The flowmeter can detect and record the forward andthe reverse components of flow velocity in the samepart of a vessel simultaneously. The probe of theflowmeter is attached to the point of maximum pulsa-tion on one side of the femoral and dorsalis pedisarteries. The proximal and distal ends of the subjects’extremities are wrapped with inflating cuffs for ECP.

Cai et al

240 Clin Invest Med • Vol 23, no 4, août 2000

P.LRQ ∆⋅η

π=8

4

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2

2

max

RUQ

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max

The pressure in the cuffs was monitored by a pressuretransducer connected to the cuffs with a special con-nector. The pressure, the time of compression, theduration of inflation and the degree of compressioncan be found from the time dependence of the pres-sure. The sustaining time of inflation was monitoredusing ear-lobe plethysmography, keeping the dicrotic(diastolic) wave higher than the percussion (systolic)wave. Heart rate was recorded from the electrocardio-gram. A 6-channel physiologic recorder was used torecord all the above-mentioned data.

A 10-turn potentiometer, with each turn setting of themulti-turn potentiometer representing a specific valueof sustaining time of inflation, was used to set this timeand to insure that a specific sustaining time for inflationcould be set quickly and accurately reproduced in dif-ferent experiments. The larger the number of turns, thelonger the sustaining time of inflation. The turn numbersettings used in the experiments were 2, 4, 5, 6, 7, 8, 9,and 10, corresponding to 80, 240, 300, 380, 440, 540,580 and 600 milliseconds respectively. The inflationpressure was controlled at either 40 kPa (300 mm Hg)or 60 kPa (450 mm Hg). For each sustaining time,counterpulsation was carried out for 5 minutes. Thechanges of velocity and volume of blood flow infemoral and dorsalis pedis arteries were observed.Counterpulsation experiments for the 8 different turnsettings made up a single group of experiments.

Since the Model F-1 Doppler flowmeter can deter-mine only blood-flow velocity, a Model QJI counter(Shanghai Navigation Instrumentation, Inc.) wasused to determine the blood-flow volume by measur-ing the area (in square millimetres) under the flow-velocity curve for 5 cardiac cycles. The average areafor a cardiac cycle was used as a relative measure ofthe flow volume. The areas taken before ECP and theareas taken during ECP with different durations ofinflation were compared. A t-test was used to com-pare data for a given subject.

Animal studies

Five dogs (3 male, 2 female, weight 15 to 18 kg)were divided into 2 groups: 3 in the experimentalgroup and 2 in the control group. The dogs in theexperimental group were given sodium pentothalanesthesia (30 mg/kg) for bilateral femoral arteriog-

raphy (Philips Diagnost-90 multifunctionroentgenogram) with an injection rate of 3 mL/s. Fiveimages were recorded automatically at 0.33, 1, 1.75,2 and 3 minutes from the start of the bolus injection.Then ECP was done for 1 hour with an inflation pres-sure of 60 kPa and sustaining times of one-quarter toone-third of the cardiac cycle. Bilateral femoral arte-riography was repeated after ECP with the same pro-cedures and under the same conditions. Data for 6experiments were obtained. The same procedure wascarried out for the control group, but without ECP.

Results

For the same inflating pressure, the forward andreverse arterial flow velocities and volumes of thelower extremities increased remarkably during ECP,but the velocities and volumes varied with the sus-taining time of inflation (Fig. 1).

The effect of ECP with various turn settingson arterial blood flow velocity

For both inflation pressures of 40 and 60 kPa, thereverse blood-flow velocity increased remarkablyduring ECP: 5.5-fold and 15-fold, respectively, in dor-salis pedis artery (p < 0.001) and 1.2-fold and 1.5-fold, respectively, in the femoral artery (p < 0.001).However, the forward velocity increased only slight-ly: 49% and 65% in the dorsalis pedis artery (p < 0.05and p < 0.01), and 13% and 32% (p > 0.05) in thefemoral artery. Although the increase of reverse flowvelocity is higher than that of forward velocity, theabsolute value of the forward flow velocity was stillhigher than the reverse. There was no correlationbetween the velocity change and the duration of infla-tion for either the forward or the reverse flow (Fig. 2).

The effect of ECP with various turn settingson arterial blood flow volume

For inflation pressures of 40 kPa and 60 kPa, both for-ward and reverse blood-flow volumes increased sig-nificantly during ECP. The average forward flow vol-ume in the femoral artery for potentiometer settings of2 to 5 turns increased by 74% and 80% over the base-line for the 2 inflation pressures (p < 0.05 and p <

Blood circulation during external counterpulsation


0.001, respectively). The increase was less significantwhen the turn numbers were larger than 6 (i.e., sus-taining time of 380 milliseconds). Meanwhile, theaverage reverse flow volume in the femoral arteryincreased about 1.4 fold. Despite the increase of timeduration, the reverse flow volume remainedunchanged or increased only slightly. Based on thealgebraic sum of the forward and reverse flow vol-umes, the average net forward flow volumes in thefemoral artery during ECP at the time settings in 2 to5 turns were increased by 45% and 64% for the 2inflation pressures (p < 0.05 and p < 0.01). The netforward flow volume started to decrease with increas-ing turn number when the turn number was largerthan 5. The minimum flow volume (at 10 turns) wasonly about 41% of that before ECP.

The forward and reverse flow volumes in the dor-salis pedis artery increased significantly during ECPwith the forward volume being higher than thereverse. No correlation was found between thechange of flow volume and the sustaining time ofinflation. During ECP, with a sustaining time of infla-tion at the 4 and 5 turn settings, the average netincrease of forward flow volume was 75% and 1.3-fold, respectively, for the 2 inflation pressures used(p < 0.05 and p < 0.01, Fig. 3).

Effect of the ratio between the sustaining timeof inflation and the cardiac cycle on blood-flowvolume in the extremities

Our results showed that there is an optimal time set-

Cai et al


Fig. 1: Forward and reverse blood-flow velocities and volumes in the femoral artery during external counter-pulsation (ECP) for various turn settings (various sustaining times of inflation setting). The top 2 curves showthe qualitative changes in forward and reverse blood-flow velocities and volumes in the femoral artery duringECP for various turn settings and the same inflation pressure. The third curve shows the sustaining time of infla-tion in the cuffs. The time is longer for a larger number of turn settings. The bottom curve is the electrocar-diogram. For small turn settings, the forward blood-flow volume is much larger than the reverse one duringECP. For larger turn settings, the forward blood-flow volume is smaller than or equal to the reverse flow veloc-ity . For small numbers of turn setting, the forward blood-flow velocity is larger than the reverse flow veloci-ty. For larger numbers of turn setting, the forward blood flow velocity is almost the same as the reverse flowvelocity. CM/S = centimetres/second.

ting (sustaining time of inflation) that produces themaximum net forward flow in the femoral and dor-salis pedis arteries for the same inflation pressureused. However, heart rate varied for different indi-viduals and at different times. Therefore, the ratiobetween the optimal turn setting and a cardiac cycleduring ECP should be used. Based on our experi-ments, this optimal ratio ranged from 0.25 to 0.34.This means that the optimal sustaining time of infla-tion is at one-quarter to one-third of the cardiac cycle.The blood-flow volume decreased when the ratioexceeded 0.34 and approached the control value. Forthe femoral artery, the net flow volume decreased

remarkably when the ratio was larger than 0.5. Thevolume can be lower than that before ECP (Fig. 4).

Effect of ECP on arterial collateraland anastomotic branches in the hindextremities of dogs

In the control group, the results of a second arteriog-raphy after a 1-hour interval are similar to those ofthe previous one. No increase in patency of collater-al and anastomotic branches of the femoral arterywas noted. For dogs under ECP for 1 hour, a signifi-cant increase in patency of collateral branches of the



Fig. 2: Effect of external counterpulsation (ECP) with various turn settings on blood-flow velocity in the arter-ies of the lower extremities during ECP (values are mean [and standard error of the mean]). For ECP with var-ious turn settings, the reverse (R, squares) flow velocity in the femoral artery (FA) and the forward (F, dia-monds) and R flow velocities in the dorsalis pedis artery (DPA) increase significantly at 40 kPa (300 mm Hg)and 60 kPa (450 mm Hg) (p < 0.05 and p < 0.01), but the F flow velocity in the FA increases only slightly.Blood-flow velocity is not closely related to the turn setting.

hind extremities was seen on arteriography.Arteriograms obtained at 1 second and 1.75 secondsshowed increasing patency of collateral branches ofthe proximal segment (above the puncture point) ofthe femoral artery, indicating increased patency ofanastomotic branches (Fig. 5).

Discussion

Under normal physiological conditions, there are 3phases of blood flow in the femoral and dorsalispedis arteries: forward flow, reverse flow and the sec-

ond forward flow. The first forward flow is caused bythe ejection of blood during systole. The reverse flowis due to the sudden closure of the aortic valve andthe drop of impulse force and a reactive force causedby filling expansion of the distal vessel wall in theextremities.The second forward flow is due to theforce of contraction of the aortic arch in expansion indiastole. However, in a small number of patients, thesecond forward flow is minimal or even unde-tectable, possibly due to the poor elasticity of vesselwall. Therefore, the blood flow in the lower extremi-ties is affected by both myocardial contraction and

Cai et al


Fig. 3: Effect of external counterpulsation (ECP) with various turn settings on blood-flow volume in arteries ofthe lower extremities during ECP (values are mean [and SEM]). For ECP with various turn settings, the forward(diamonds) and reverse (squares) blood-flow volumes in the lower extremities increase, especially for turn set-tings from 2 to 5). The net forward (circles) blood-flow volume increases significantly for turn settings from 2to 5 (p < 0.05 and p < 0.01), but drops back significantly, even to a value lower than that before the ECP forturn settings more than 5. DPA = dorsalis pedis artery, FA = femoral artery.

the 2 reactive forces.Under our experimental conditions, arterial blood

flow in the lower extremities was mainly determinedby the following force components: • The effective force of ECP; that is, the compres-

sive force on the arteries of the lower extremitiesproduced by cuff inflation during ECP, causing theblood in the lower extremities to flow back intothe aorta.

• The negative force produced by the sudden expan-sion of arteries due to the release of compressionfollowing a rapid deflation of the cuffs, causingblood to flow to the arteries in the lower extremi-ties from the aorta.

• The reactive force produced by the resistance ofaortic blood flow to the force of arterial blood inthe lower extremities, resulting in pressure on theaorta, and the reactive force produced by the fill-ing expansion of the aortic arch walls, resultingin blood flow to the lower extremities; or thereactive force produced by obstruction of bloodflow from overexertion of pressure on arteriesand the filling expansion of arteries in the lowerextremities, rendering blood flow back to aorta.

• The contractile force of myocardium and aorta;that is, the force produced by contraction of the

heart during systole and contraction of the aorticarch during diastole, ejecting the blood from theleft ventricle and aorta distally.

In routine ECP, the action of ECP, the negativeforce produced by it and the myocardial contractileforce are basically stable, except that the reactiveforce varies in accordance with the sustaining time ofinflation. However, the change of sustaining time ofinflation changes the algebraic sum of the negativeforce, the contraction force by myocardium andaorta, and the reactive force.

Why, then, do flow velocity and flow volumechange with the sustaining time of inflation for thesame pressure? In our experiment, the deflation timewas changed to change the sustaining time of infla-tion. According to our experimental studies, for thesame sustaining time of inflation, the key factor thataffects the flow volume in the lower extremities is thephase when the deflation is applied (i.e., the phase inwhich a negative force is produced in the arteries oflower extremities). Our experiments have shown thatoptimal results can be obtained when the inflationstarts in the reverse flow period and the start time ofdeflation is near the end of the second forward flowof diastole. In this condition, the active force from theaortic wall during diastole, the negative force of thefemoral artery and the myocardial contraction forceare in the same direction and applied in sequence,resulting in a strong and steady active force to createrapidly a massive flow of blood from the aorta intothe femoral artery. On the other hand, an earlier orlater start of the deflation time makes the sustainingtime of inflation too short or too long, so that the 3force components are activated at a disordered paceand may overlap in time. Therefore, the effects of theforce components may be cancelled, resulting in aless efficient effect so that the flow velocity and flowvolume in the forward direction are close or equal tothe reverse ones, or even result in a negative effect(i.e., transient ischemia in the lower extremities). Theduration of blood flow in the arteries of extremities isreduced with larger sustaining time of inflation with-in a cardiac cycle. The blood volume in the extremi-ties is, therefore, reduced. On the contrary, the dura-tion of blood flow in the arteries of extremities isincreased, causing increased blood volume in thesearteries. In the treatment of ischemic heart disease,



Fig. 4: The correlation between the ratios of the sus-taining time of inflation to the cardiac cycle (solidcircles) and the net forward flow volume (open cir-cles) in the lower extremities. The curves show thatthe maximum net forward blood-flow volumeappears at turn settings 4 and 5, corresponding toone-quarter to one-third of the cardiac cycle. Forturn setting greater than 5, the net forward bloodflow volume drops with the number of turn setting,even to a value lower than that before externalcounterpulsation.

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Fig. 5: Arteriographic changes in the femoral artery before and after external counterpulsation(ECP) in dogs. Top left — control dog, top right — control dog 1 hour later. Bottom left — studydog before ECP, bottom right — study dog after 1 hour of ECP.

ischemic cerebrovascular disease and eye disease,longer sustaining time of inflation equivalent to 50%to 60% of the cardiac cycle is often used. In thesecases, blood-flow volume in the extremities is likelylower than that before ECP. This may result in a tran-sient ischemia of the extremities, causing limb numb-ness in some patients.

Generally, most of the collateral and anastomoticbranches of the lower extremities are closed.However, during vigorous exercises or when thearteries of lower extremities are stenosed, part of col-lateral and anastomotic branches might open reflexlyto augment blood supply to the extremities. Onceinsufficient blood supply occurs as a result of the lossof or an inadequate compensative mechanism, somedegree of ischemia will occur, leading to relatedsymptoms, such as feeling cold, pallor, pain, inter-mittent claudication or even necrosis. Femoral arteri-ography in dogs showed that patency of collateraland anastomotic branches of the femoral artery afterECP increases remarkably, which could result in agreater blood supply to the extremities, including theischemic tissue covered by the stenosed or obliterat-ed arteries, leading to the relief of the extremityischemia.

We conclude that, with an adequate sustaining timeof inflation, ECP is capable of augmenting blood sup-ply to the extremities. The mechanism of the aug-mentation can be explained as follows. Vessels of theextremities are compressed and released alternatelywith the inflation and deflation of the cuffs. Thisresults in the increase of intravascular pressure differ-ence, which, in turn, increases significantly the veloc-ity and volume of forward and reverse blood flowpassing through the vessels. This has an impact on thestenosed or obliterated vessels and makes them dilat-ed or even recanalized. For optimal sustaining time ofinflation (in the range of one-quarter to one-third ofthe cardiac cycle), the forward flow volume greatlysurpasses the reverse one, resulting in a significantly

increased net forward flow volume in a cardiac cycle.Furthermore, there is increased patency in the collat-eral and anastomotic branches of the lower extremi-ties after ECP, greatly increasing the blood flow in theextremities. Our study suggests that external counter-pulsation could be an effective modality in the treat-ment of arterial obstructive diseases of extremities,such as atherosclerosis, Buerger’s disease, delayedhealing of long-bone fractures and peripheral circula-tory insufficiency.

References

1 Cai D, Wu R, Lu W, Huo L. Effect of external coun-terpulsation on cardiac function and hemodynamics indogs. Acta Physiol Sinica 1980;32(4):357-63.

2. Cai D, Wu R, Lu W, Huo L. Effect of external coun-terpulsation on experimental acute myocardial infarc-tion in dogs. Shanghai Med J 1982;5(1):5-7.

3. Cai D, Wu R, Shao Y, Xie Y, Wang C, Huo L. Anexperimental and clinical study of external counterpul-sation on certain diseases of cerebral vascular insuffi-ciency, a preliminary report. Shanghai Med J 1981;4(11):15-8.

4. Soroff HS, Hui J, Giron F. Current status of externalcounterpulsation. Crit Care Clin 1986;2(2):277-95.

5. Zhao G, Li S, Wang Z, Gan S, Chen S, Chen X.External counterpulsation in the treatment of cerebralthrombosis. Shanghai Med J 1985;8(10):572-5.

6. Ye G, Wang W. A bidirectional ultrasonic Doppler forblood flow velocity measurement with direct single-sideband separation. Med Instrum 1982;6(1):8-14.

7. Ruch TC, Fulton JF. Medical physiology and bio-physics. vol 2. Beijing (China): Science Publisher;



Correspondence to: Dr. Dawei Cai, ExternalCounterpulsation Laboratory, The Clinical MedicalCollege, Shanghai Medical University, 85 Wu JinRd., Shanghai 200080, People’s Republic of China;fax 011 86 21 63240825, [email protected]

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