Methodological Approach on Artificial Heart Control

Copnigh t © IFAC Control Aspect s of Prosthetics and Orthotics Ohio , l'SA , 19H2

METHODOLOGICAL APPROACH ON ARTIFICIAL HEART CONTROL K. Atsumi, I. Fujimasa and K. Imachi Institut e of Medical Electronics, Faculty of M edicine, University of Tokyo, Tokyo, japan

Abstract. Artificial heart study is rapidly progressing and experimental animal with artificial heart became able to survive more than 9 months, however, its contro l method is yet in primitive stage. In this paper, the present status of artificial heart and its control method were introduced, and then discussed about the methodology of artificial heart control method establishment. Keywords. Artificial heart; Circulatory system; optimal control; Simulation model; Physiological parameter. 22 1 days in 1979 by Kolff and 288 days in 1980 by Atsumi(1981). These are shown in Fig. 1.

I NTRODUCTI ON The idea of artificial heart(AH) has generated from a concept that a biological heart is only a pump to send blood from vein to arteries. As a fact, it is not so difficult to send whole blood which return to right atrium, to arteries with AH blood pump. However, to co ntrol the circulatory system including AH, is not so easy. The most important work in AH is to send optimal blood flow to tissues and organs according to their demand. In a biological heart, cardiac output is controlled under feedback mechanism through neurohumoral regulatory system. On the other hand,in AH system, as the blood pump is completely isolated from nervous system and has not any sens itivity to catecho l am ine, establishment of artificial control algorithm of blood pump is necessary to determine adequate cardiac output for tissues and organs. However, there are many obstacles for establishment of AH co ntrol metho d. In this paper, the authors try to introduce a present atatus of AH control and to mention how to approach to the goal of AH control.

IU ~-----------------------

U

Fig. 1. PRESENT STATUS OF AH RESEARCH The artificial heart study has been begun at 1957 by Kolff and Akutsu, and the author has also begun to study of AH two years later. However, in the first la years, many troubles such as thrombus formation in the blood pump, pump rupture, miscontrol of AH, etc., had disturbed to get lon g survival of experimental animals. And it was 1970 when the first calf implanted AH had survived more than 100 hrs in Kolff's laboratory . After that, AH study began to develop rapidly and survival period of AH animal also prolonged year by year such as 25 days in 1973 by Akutsu, 95 days in 1974 by Kolff, 145 days in 1976 by Nose, 184 days in 1977 by Kolff, 210 days in 1978 by Kolff,

le

IJ

11

1)

"

,~

a

"

81

(Yu.)

Prolongation of the longest survival period in TAH animal in the world.

Until now, 11 animals equiped with AH survived more than 6 months in the world.(Table 1) These progresses in AH study have enable to use AH in patients as circulatory assist device, and until now, more than one hundred clinical cases were reported in the world. On the other hand, total artificial heart(TAH) in which natural heart function is totally substituted, is also try to use for patient as a connection to heart transplantation. Artificial heart system is composed of blood pump, drive and control unit, and measurement apparatus.

11 7

K . Atsumi,

li S

Table 1.

1. Fujimasa a n d K . lmachi

TAH Animals Surv i ved Over 6 Months in the World. 8lood

Fac i l i ty

An i rnal

Su rvival Days

To ky oUniv .

GOllt

188

So<

Utolh Univ .

Calf

168

J,

Type

p~

Valve

Haterhl Av(oth'ne/ Avco-+Pb lyureth.r'Ie

SS

Anti coagulant None

810mer

H$/BS Nat

Persantlne. Aspirin

( a uS!! of Death

Human accident

left heart failure

To 'oo yoUn l v.

Goat

143

So<

Polyurethlne

SS

Heparin ( 68-24] )

Pannus. Reoperation

10ky oUn; y.

Goat

131

So<

Polyurethane

SS

None

Pe r ipheral circ ulato ry, Ins uff ici ency Pannus. 61-bleeding

Ulah Url1v.

Calf

111

J,

Blcmer

8S/Nat

COl6Tlolld in. Aspirin

Utah Univ.

Calf

117

J,

BIOI'Ier

8S/Nat

Coutna din

Uldlh UniY

Ca, f

110

J,

Btomer

BS/ fI.t

None P)

Srr llnU nlv .

Calf

19'

Oia phraC1fl

Prlle-th ane

SS

Hersny Me dic a l ( enter

Calf

190

Dia phrAgm

Bl(11'1er

SS

Coumadin

Utah Univ .

Calf

184

J,

Blomer

8S/Nat

Persanl;"e, Coumad i n. Aspi r in

Pannus. Reape rat ion

Uta h Uni v.

Calf

183

J,

as/Nat

Persantine. CO\IMdln. Aspirin

lung edema. Hemiplegia, Pannus ( Acc ident )

81011'1er

Sepsis , Pannus

Rupture of

b l ood plnp

Blood Pump A sac type pump as shown in Fig . 2, has been usin g in thi s institute, which i s fabricated wit h med ica l grade polyvinyl ch l oride(PVC) paste and coated its blood contact surface with Avcothane. Two Bjork-Shiley va l ves with 18 mm orifice diameter are incorpolated at the inl et and out let port, respectively. The sac vo l ume is 90 ml and max i mum output is 6 l /mi n. Drive and Control Unit The bl ood pump is driven by positive and negative air pressure generated from drive and contro l uni t. In the drive and control unit, po sit ive and negative air pressure generated from air compressor and vaccum pump respecti ve l y, are regulated at certain setti ng l eve l with pressure regulated valves and charged in pressure reservoir. The regulated positve and negative pressure are send to blood pump alternatively by chang in g with electro -ma gnet i c va l ve under the electlic pu l se generated fro m co ntrol unit.(Fig. 3) As the fun ct ion of drive and con trol unit, positive and negative pressure le ve l , systo li c duration in one pulse and pulse rate are cha ngeab le.

Fig. 2.

AH bl ood pump developed in the authors l aboratory.

Many the other t ypes of drive mechanism such as DC motor, Stirling engine, so len oid, axia l flow pump, etc., are developing in many institutes, but they are not yet practica l at present stage. Measureme nt Apparatus It i s very diff i cu lt to measure many physiological data noninv as i ve l y with present measurement technique. And traumatic measure me nt method often induce infection or thrombus forma tion and disturb to get l ong sur vi va l of AH anma l s . So, in th i s ins titute, animal experiments are devided into two types. One is a experiment for ge tting l ong sur vi va l of AH animal in which only cardiac output is measured by el ectra - magnet i c f l ow probe, and anot her i s exper i me nt to measure many physio l ogica l data such as blood pres sure(arterial pressure, venous pressu re, etc . ), blood flow

Fi g. 3.

Sc hematic figure of air driven type AH drive unit.

(organs blood f l ow , ti ssu e blood flow, etc.), gas tension(pH, 02 and C02 of blood and tissue), meta boli sm( bl ood l actate,pyruvate) , blood and bl ood chemical da ta, etc ., to clarify their cor relati on wi th AH pa rameter. As measureme nt apparatus, electro-magnetic blood flow meter, electri c blood press ure meter, ti ssue blood fl ow meter util i zin g hydro gen clearance, med i ca l mass spectromete r, blood chemi ca l ana l yzer, etc. are used in this in stitute.

Methodological Appioach on Arti f i c ial Heart Con t r o l

Present AH Control Methods and Their limit The AH control methods performed in many institutes at the present time, are thought to be very primitve stage. Mainly,three types of AH control method are performing. Control under Starling's law. In 1962, Kolff had introduced a concept of Starling's law in natural heart as an AH control method, in which whole the blood returned to right atrium was sent to systemic arteries. And in practice, driving condition of AH is determined as the right and left atrial pressure are maintained at near zero level. This control method has been widely adopting in many AH research institutes without precise evaluation of propriety of this metrod, because this concept is very easy ~~ understand and control method itself is comparatively simple . Control of cardiac output . The author also also performed AH control under Starling's law until 1973. However, by this control method, cardiac output of AH animal was often increased gradually to twice of normal level. And high output syndrome in which severe circulatory insufficiencies were induced, was observed in many AH animals. So, new control method in which cardiac output is maintained within normal level(80 - 100 ml/Kg/min.) were developed by the author's group and has been using since that. By adopting this AH control method, survival period of AH animal has rapidly prolonged and survival state has been remarkably improved. In this method, output of right blood pump is regulated within 80 to 100 ml/Kg/min and the left side pump send the whole blood return to the left atrium to systemic arteries(Atsumi, 1975). Control of arterial pressure. Pierce(1976) developed an automatic control system in which output of the left AH pump was regulated

as the mean arterial pressure was maintained at constant level and the right blood pump output was decided as much as possible within the range that left atrial pressure did not exceed the normal level . This method also revealed good results and he succeeded to survive a calf for 190 days. These control method seem to satisfy adequately the demand of AH animal at the rest condition(including stand up, eat and drink). And it is difficult to make a discrimination among these method. However, AH control method is not yet completed. The present AH control method can not satisfy the demand in special status shch as during exercise,sickness, pregnancy or delivery, etc .. So, farther investigation to establish AH control method is thought to be very important .

METHODOLOGY OF AH CONTRO L METHOD ESTABLISHMENT Concerning to AH control method establishment, it is important to develop a methodology to approach to the final goal. Figure 4 is schematic diagram which shows how to develop the AH control method. Many physiological data are measured from biological system with natural heart and biological system with AH under some load tests such as exercise, pharmacological test or abnormal hemodynamic test. An AH circulatory dynamic s i mu lation model becomes possible to construct from these data and AH control logic can be made from this model. Pysiological data getting from the AH circulatory system under this co ntrol logic are compared with the data from biological system with natural heart and evaluation of propriety of this control logic is made. The AH circulatory dynamic model is modified in consideration of the evaluation result.

Biological System with :~atura l Heart

Giological System with AH

Fig . 4.

11 9

Schematic diagram of methodology for develpment of AH control method.

K. Atsumi, I. Fujimasa and I. Imac hi

120

The physiological parameters concerning with AH control are shown in Table 2. They are classified into two categories; Rapid response parameter and slow response parameter. The most important thing is that what parameter should be chosen as objective parameter and evaluation parameter of AH, among them. On the other hand, in AH system, the parameters shown in Table 3 are related to AH control as operational parameter. Concerning to these parameters, analysis of AH blood pump function is also important work. Physiological Parameter Related with AH Control.

Table 2.


c: ... 0
... ...'"

.:.:.'" uo. ::::J CT


c: ... 0
...

...'" '"

~ 0. 0 (/)

Blood flow rate Cardiac output(R & L) Organ & tissue Microcirculation Blood pressure Arterial pressure Pulmonary artery pressure Atrial pressure(R & L) Central venous pressure Gaseous metabolism Blood gas Tissue gas Respiratory gas Water metabolism Circulating blood volume Extra cellular fluid urine volume hema tocrit Hormone Glycolysis Blood lactate Pyruva te Acid-base balan~~

Table 3.

Parameter Influenced on AH Blood Pump Output .

Flow resistance of pump element Cannula Valve Connecter Driving force in AH system Driving air pressure(LPS,RPS) Vaccum pressure(LPD,RPD) Pulse rate(f) Systolic/diastolic(r) Driving force in biological system Right atrial pressure(PRA) pulmonary artery pressure(PPA) Left atrial pressure (PLA) Aortic pressure . (PA) Pump properties pressure loss through sack wall (PMSL,PMDL,PMSR,PMDR) Pump volume

In the following session, some investigation that are now undergoing in the author's laboratory are introduced.(Imachi, 1978, 1980) Parameter to Evaluate Propriety of AH Control In the study of AH control, one of the bottleneck was that there was no good evaluation parameter of propriety of AH control method. Though in many laboratories including author's laboratory, various kinds of hemodynamic data such as blood pressure, blood flow rate, blood gas tension, etc., has been measured, precise evaluation was difficult only from these data. And then, survival period of AH experimental animals has been an only standard of judgement for propriety of AH control method. It is well known that under hypoxia, anaerobic glycolysis will be occured and lactate will be generated into blood, So, if AH control method is improper, adequate blood does not send to peripheral system, and blood lactate level is thought to increase . Then, recently authors thought that blood lactate might be able to utilize as a physiological parameter to evaluate of propriety of AH control method, and basic study has been begun under the following method. Three grade treadmi 11 exerc i se (1 .7, 3.4 and 6.7 Km/h) for 1 or 3 minutes was performed for pre-operative and AH equipped goats. In AH goats, their cardiac output was regulated at the level of 70, 80 ml/Kg/min and maximum in which whole blood return to right atrium was sent to arteries, before, during and after treadmill exercise, though it was usually maintained at 100 ml/Kg/min. Blood lactate was measured intermittently in these experiments. Figure 5 shows the comparison of blood lactate change with treadmill exercise(1.7 Km/h,l min) between before and after putting on AH. In this case, preoperative goat could not walk well on treadmill and blood lactate increased in spite of low speed and short term exercise. However, at the condition of CO=Max., blood

•

o o 6.

Pre - ope ra tion TAH 1 week TAil 2 wee ks TAH 7 we eks

C.O. = Ma ....

=

o

~I--~------~------~. O------~15------~m E~e;r;: 1 se

{1.7 v,.,/ n , 1 "'i n.'

Fig. 5.

Comparison of blood lactate change with treadmill exercise (1.7 Km/ h, 1 min.) between before and after putting on AH

Ne thod ol o g i ca l Appr oach on Arti f i c ial Hea rt Co ntr o l

lactate level was less than preoperative value after 1 week of surgical operation of AH implantation. And blood lactate level decreased more in accordance with recovery of AH goat from the invasion of surgical operation, for same grade treadmill exercise. Figure 6 shows a comparison of blood lactate change with treadmill exercise(6.7 Km/h,l or 3 min . ) between another control goat and AH goat under maximum cardiac output. It can be known from this figure that blood lactate level increase in proportion to treadmill time, and for 3 minutes exercise, elevation of blood lactate level is almost same between control and AH goat, however its recovery to the normal value is faster in the AH goat than in the control goat. For 1 minute exercise, the increase in blood lactate level of AH goat is slighter than that of control goat. Figure 7 shows the influence of cardiac output on blood lactate level during treadmill exercise(1.7 Km/ h,3 min.). In this grade exercise, there is not so much difference in blood lactate level elevation between CO=80 and CO=Ma x., whereas significant change is observed in the state of CO=70.

12 1

From these experiments, it can be concluded that the blood lactate is one of the most adequate parameter to evaluate the propriety of AH control method. Analysis of AH Blood Pump Function In order to construct AH circulatory model and to realize automatic control system, AH blo?d pump function must be analyzed theoret1cally . The factors influenced on AH blood pump function are shown in Table 3. In pulsatile pump, pump output is decided as the minimum between blood volume which is to be flowed into the sac during diastolic phase(SVi) and blood volume which is to be sent out from the sac during systolic phase( SV o )· In general, the total head loss on t~e pump inflow side(hit) and pump out flow slde(h ot) are given by

(1) (2)

t r e adm il l spe ed

100

Control qoat

6 . 7 !(m/ M

6 : 1 !'lino eX f'rcis e .

: 3 min . exerc i se

where Kit and Kot are the total loss coeffic~ent in inflow side and outflow side, respect1vel y , and Oi, 00 are volume flow rate .

80

SV 1. 2e

O·1/ h(l+r) (2gh it / Kit ) 1/ 2/ f*(l+r)

SV 0

°o*r/ f*(l+r) (29h

G ! L 3

JO :'.eCG','e r'l

Fi g . 6.

100

80

15

20

811 8

Treadmil l exerc ise at 18t h day 11.7 K"/h x 3 Mln. 1 Q)

e.o.

When

Mu

() : e.o .

80 ml / Kg f mi n .

(i : C . O.

70 ml / lC g / min.

f . Cl

<

=

f

co'

if

f

<

==

f

.

Cl'

(O-b in Fi g. 8 ) if

40

f

>

CO = Sv 1.*f=(29h.1 / K.1 )1 / 2/( 1+r) t t (b-y in Fig. 8)

10 Recover y (min.)

15

Influence of cardiac output on blood lactate level during treadmill exercise (1.7 Km/ h, 3 min.),

( 5)

f Cl, .

When

CAP O _ E

( 4)

In the pulsatile flow, inflow volume(SVi) and outflow volume(SV Q) per one pul se are given by Eq. (3) and (4), respectivel y . If sac effecti~e v?lume is VD, actual pump stroke volume 1S glven as the minimum value among VD, SVi and SV o . So, if fci and fco are pulse rate ,when SVi = VD and SVo = VD, respectively, card1ac output(CD) is given as follows.

60

Fig . 7.

/ K )1 / 2*r/ f*(1+r) ot ot

{.~; . ~ . )

Comparison of blood lactate change with trreadmill exercise (6.7 Km/h, 1 or 3 min . ) between a goat with natural heart and one with AH .

~o .

( 3)

if

f

< =

f

(6)

co'

20

(O-a in Fig, 8) if

f

>

( 7)

f co '

CO = SV 0 *f= (2gh t / K t)1/2*r/( 1+r) 00 (a-x in Fig. 8)

( 8)

K. Atsumi, I. Fujimasa and K. 1mac hi

122

From these equation, the relationship between CO and f is given by O-b-y or O-a-x in Fig. 8.

+hat

CO

f

z

t

Kat hit

t

Kit

y

x

a

fea

fei

In this figure, if the parameters increase, the curve will move to the direction shown by the arrows. Figure 9 shows the actual relationship between cardiac output and puse rate obtained in mock circulatory system . The relationship between cardiac output and systolic diastolic ratio(r) is shown in Fig.10 from Eq. (6) and (8). These are hyperbalia and will move to the direction as shown by the arrows when parameters change to increase . The curve d-e is decided by the outlet condition and the curve e-f is decided by the outlet condition. Figure 11 shows the actual relationship obtained from mock circulatory system when parameters are changed. Figure 12 shows the comparison between theoretical value and measured value. These figure revealed that AH blood pump function well expressed thoretically.

fea

Pulse rote Fi g . 8.

Theoretical relationship between cardiac output(CO) and pulse rate(f).

Fig.ll. DP!+)

DP( -J

S/D

(1'1]1

( rrt'!HQ)

. 'J l

Fig . 9 .

o

170

-~()

0.67

91)

o

220

-30

O,f.1

<)()

A

170

30 n . f.7

(,0

-,~ " 1'('

Actual relationship between cardiac output and S/D ratio

v6~S~'e

ill"l1 F"III

Actual relationship between cardiac output and pulse rate.

I I

>\. .I ~

/

. : Mea sured

- : Ca l cu l ated r • a.985

.

\ \

\

•

.".~-

--- ---... --

S/D Rotlo

Fig.12. u

c

2

Simulation Model of AH Circulatory System

-1 I I

,I Fig. 10.

Comparison between thoretical value and measured value in CO - r relationship .

Theoretical relationship between cardiac output and systolicdiastolic ratio(r).

From many physiological data, simulation model during treadmill exercise was constructed . The model was constructed under the following two assumptions : 1) Circulating blood volume would not be changed during exercise . 2) Total peripheral resistance was devided into muscle

Me thodolog i c al Appr oach on Artifi c i a l Hea rt Contr o l

J

23

parts(RSM) and non-muscle parts(RSN). Their ratio was 4 to 1 at the rest condition and changed to 1 to 3 during treadmill exercise. The constructed model is shown in Fig . 13, which is composed of 6 compartments. Blocks 12 through 17 show the arterial system. Blocks 12 and 13 calculate aortic pressure (PA), while 15 and 16 calculate blood flow in muscle parts and non-muscle parts . Blocks 21 through 23 calculate exercise information. F3 and F4 show the change in vascular resistance in muscle and non-muscle parts, and F5 gives the venous pressure rise due to the rise in venous tension during exercise. Blocks 24 through 59 show the venous system. Through these blocks, venous pressure(PVS), venous returned blood flow rate(OVO) and right atrial pressure(PRA) are calculated. Blocks 63 through 69 show the pulmonary system. In block 64, pulmonary arterial pressure(PPA) change is calculated. Blocks 65 through 67 calculate pulmonary vein blood flow rate(OPO), and blocks 68 and 69 calculate left atrial pressure(PLA) . Blocks 101 through 119 show the right AH pump function. Block 110 and 114 calculate the total inflow and outflow pressure gradient (HTIR, HTOR) in the righr AH pump, respectively. Blocks 111, 112 and 113, calculate Eqs. (5), (6) and (8), respectively. Actual pump out ability(ORN) can be obtained by block 115 as the minimum value among OR1, OR2 and OR3. In blocks 116 through 119, actual cardiac output(ORO) is decided . When ORN is small er than OVO, the pump can pump out the blood inside the right atrium and large vein until right atrial pressure becomes critical closing pressure(CCP). And after

Fig.14.

Simulation result of treadmill exercise with sufficient driving conditin.

PRA become equal to CCP, ORO = Ova. Blocks 121 through 139 show the left AH pump function . The calculation procedure is the same with the right AH pump. The model was calculated with DDS(Digital Dynamic Simulator) program in Large Computer Center of Tokyo University. Fi gure 14 gives calculation result using this model. Total peripheral resistance change data obtained from AH animal treadmill exercise experiments were given in block 21 and 22. Venous pressure rise due to venous tension rise was postulated at some value. And AH

r - - - - - . . - - - - - - - - - - - - - - - -- ______________ ., I 2..:. ~3 ,,~ Fl, 21 F5 : : I '~ "

J\ ... Ex,""

"·,c, , . L...:...._____

'c..:::~::.Jt

:!" ':

~

'=-

I- ', , ~

"' Ex -
.

,

Y

..J'L

I·

I

I O"" ",,,-,,""'-''''-'''',-,-,,1N""
I

) .... ~.. 1 to .. t - - - - - - . _ _ _ _ _ _ _ _ _ _ _ .J. _ _ _ _ _ _ _ _ _ _ _ _ _ _ .... I

I

I

: I

:~j L • r) 1)8 ; l O '" ll'i ~'1l > 1)

!f

1taA~> ~~ ~

Artificial H~art Circulab'y DynamicsOVl

I-.......L.--'

If PLA H C? OLO • 1PO

OO R > 0 If PRA:> CCP

lRO • 1R4

,,

If PRA teCP

1RO • 1VO

: PUL"IONAR Y SYS TEM I ~~~~'1P FUNCTI O~ L-._ _ _....I L ___________________________ .l... ______________

Fig.13.

Simulation model of AH circulatory system during treadmill exercise.

K. Atsumi, I. Fu j ima sa and K. Ima c hi

124

driving condition such as positve and negative REFERENCES driving pressure in right and left pump(RPS, RPD, LPS, LPO), systolic duration in right and Atsumi, K. (1975). Hemodynamic analysis on left(SOR, SOL) and pulse rate(PR) were given prolonged survival cases of artificial in this model. Figure 14 is a result in which total heart replacement. Trans . A.S.A.I.O right and left driving pressure is sufficient 21,545-55. for pumping out the whole blood returned to Atsumi, K. (1981). Three goats survived for venous system during exercise. The result 288 days, 243 days and 232 days with reveals that the model well simulate an animal hybrid total artificial heart. Trans. experimental result under the same driving A.S.A. 1.0., 27, 77-83. condition and treadmill speed, which is shown Imachi, K. (1978). Circulatory dynamic model in Fig. 15. and its application to artificial heart control. Proceedings of MEOIS'78, 546549. Imachi, K. (1980). In Lindberg and Kaihara (Ed.), MEOINFO 80, North-Holland Pub. Comp. 1144-1148. Pierce, W. S. (1976). Automatic control of the artificial heart. Trans. A.S.A.I.O . .IT.:. 347-356 .

Fig .15.

In-vivo result of treadmill exercise with sufficient driving condition.

CONCLUSION Though AH animal became able to survive for more than 9 months, AH control method is yet in primitive stage. In this paper, the auther introduced present status of AH study and its control method, and discussed about how to approach to the goal of AH control. And finally, some example studies undergoing in the author's laboratory to approach the goal, were reoported. To establish a complete automatic control logic of AH system, it is important to analyze the mechanism of circulatory system precisely, and to construct simulation model of AH circulatory system. The simulation model presented in this paper, is constructed from only the data got from AH animal experiment. Though it farely well simulates actual circulatory system, farther investigation will be required to construct a complete model. As for another future problem, what parameter should be chosen as the objective parameter of AH and how to get feedback signal for control from biological system, should be solved.