Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
:~ 3 ~
BIOME~ICAL METHOD ~ND APP~RATUS FOR CONTROLLING
T~E A~MINISTR~TION OF THERAPY TO A PATIENT
IN RESPONSE TO CHANGES IN PHYSIOLOGIC DEMAND
sAcKGRo~ND o~ T~IE INVENTION
The stroke volume of the heart is defined as the volume
o blood expelled by a ven-tricle in a single beat. It is equal
-to the difference between end diastolic volume and end systolic
volume. The importance of stroke volume in determining the state
of the heart is evident in that the cardiac output, i.e., the
total volume of blood pumped by a ventricle during a period of
time, is equal to the product of the heart ra-te and the stroke
volume. The stroke volume may be increased either by decreasing
the end systolic volume, implying increased myocardial
shortening, or by increasing end diastolic volume. Increases in
ventricular distention result in greatly increased wall tension
to develop the same intraven-tricular pressure during ejection.
In normal human subjects with healthy hearts, the
stroke volume of the heart remains relatively constant over a
wide range of exertion, from minimal activity to high physical
exertion. The increases in cardiac output under stress are due
primarily to increased heart rate, at least up to a point. Also,
in normal human subjects, increases in stroke volume are reported
only under maximal exercise conditions as the heart rate tends to
level of. In contrast, with patients suf-fering from third
degree heart block where a fixed rate cardiac pacer is
determining the heart rate, increased cardiac output during
exertion is due principally to increased stroke volumeO ~owever,
stroke vclume cannot increase by more than a factor of 2 to 2-1/2
which limits the exercise capabilities o~ these patients.
l3~3sa~
secause stroke volume, in individuals with a fixed
heart rate due to heart block/ is a useful indicator oE
cardiovascular load, and since studies indicate a constancy of
stroke volume under sub-maximal exercise, it would be
advantageous to have a cardiac pacer having a variable rate and a
means for varying that rate as a function of stroke volume. In
such an arrangement, during exercise, the pulse generator would
be designed to sense the increase in stroke volume due to changes
in physiologic demand and would function to increase the pulse
rate so as to bring the stroke volume parameter back to i~s
original value.
In a paper entitled "Continuous Measuremen-t of
Ventricular Stroke Volume by Electrical Impedance" published in
the Cardiovascular Research Center Bulletin, Volume 4, No. 4,
April-June 1966, Pages 118 through 131, L. A. Geddes and his
associates at the Baylor University College of ~edicine in
Houston, Texas reported on an approach for measuring stroke
volume by sensing changes in impedance between two spaced
electrodes disposed within the ventricular cavity. It was
theorized that the blood in the ventricle constitutes an
electrical conductor of irregular and changing shape such that
spaced electrodes placed in the ventricle could be used to sense
instantaneous impedance variations observed between the
electrodes as the blood fills and leaves the ventricle.
In the Knudson et al U.S. Patent 4,313,442, there is
described a cardiac pacer whose rate of generation o~ pacer
pulses is controllable as a ~unction of changes in the detected
P-wave rate. In that arrangement, a lead having a stimulating
electrode at its distal tip is positioned so that the electrode
abuts the apex of the ventricle. That lead has further sensing
electrodes disposed a predetermined distance proximally of the
tip of the stimulating electrode so as to be located near the
upper right wall of the atrium. The atrial (P-wave) activity
picked up by the sensing electrodes is processed in
- ' ~ .
`L3139~0
suitable circuitry ~nd used to vary the interpulse interval of a demand-
type cardiac pacer. In that the P-wave activity is indicative of
physiologic demand, the variable rate pacer of the aforesaid Knudson et al
patent permitted the stimulating rate ~o be altered as a function of body
needs.
When the present Jnvention is used in conjunction with a cardiac
pacer having a variable rate capabili~y, P-wave activity is no longer an
indicator of physiologic demand, but instead, changes in stroke volume are
detected and a signal is developed which is proportional to those changes.
By applying that signal as a control signal to the timing circuit of a
demand-type cardiac pacer, the pacer pulse ~enerator will output
stimulating pulses in accordance with the physiologic demand indicated by
stroke volume changes. The method and apparatus of the present
invention as applied to a cardiac pacer involves varying the ventricular
pacing rate in such a fashion as to minimize changes in stroke volume.
Thus, during exercise, the sensin~ circuitry to be describecl senses changes
in ventricular volume or stroke volume and then alters the operating
parame~ers of the utili2ation device. For example, in a cardiac pacer
application, increases in stroke volume may be sensed and the resulting
control signal may be used to increase the pulse rate so as to bring the
stroke volume back to its original value. This rnay be dsne either with
respect to an absolute reference stroke volume or, as in the system of the
aforereferenced Knudson patent, by sensing only changes in stroke volurne
and altering the rate to minirnize the changes.
SUMMARY OF THE INVENTION
In carrying out the instant invention, a lead arrangment having a
stimulating tip adapted to abut the apex of ~he ri8h~ ventricle has further
sensing electrodes in the form oE either axially spaced apart rings or rings
which are split so as to form two radially spaced arcuate segrnents which
are disposed proximally of the tip by a distance which loca~es those
~3~3~a
sensing electrodes or se~ments solely within the ventricle. A relatively
low frequency, low amplitude, alternatin~ current signal, typically in the
range between 0.5 and 5 K~lz and between l.0 and l0 microamperes (RMS)
is applied across the spaced electrodes and it is found that the beating
action of the heart and the accornpanying changes in b~ood volume within
the monitored ventricle results in a modulation of the AC signal, the
modulating envelope being proportional to stroke volume. The modulated
carrier wave is then filtered, demodulated, and signal processed to
produce a current signal which is proportional to the stroke volume of the
heart. This current may be injected into the timing circuit of a cardiac
pacer whereby the escape interval of the pacer is controlled as a function
of changes in stroke volurne. Alternatively, the demodulated wave:form or
the current signal proportional to changes in stroke volume may be used in
other biomedical electronic apparatus such as a dru~ dispensing pump,
surgical monitoring equipment, a cardiac output computer, an arrithymia
monitor, etc.
DES~RIPTION OF THE D~AWINÇS
Figure l represents by means of a block diagram a system
incorporating the present invention,
Figure 2 illustrates one forrn of lead arrangement useful in
practicing the invention;
Figure 3 illustrates an alternative lead construction which may
be used in practicing the invention;
Figure 4 is an electrical schematic diagram of a circuit for
producing a control signal proportional to changes in the stroke volume of
a mammalian heart from an absolute reference;
Figure 5 is a modification of the embodiment in Figure 4
whereby the control signal is determined by changes in stroke volume
without reference to a pre-established threshold; ancl
Figures 6a through 6i illustrate waveforms at various points in
the circuit arrangement of Figure l~.
.~3~3~
DESCRIPTION OF THE PREFEF~ReD EMBODIMENT
Referrin8 first to Figure 1, there is shown an ~cillator circuit 10
whose output is ~upled throu~h a constant currcnt source 11 to first and
second spaced apart elec~odes 12 and 13 that are located in the ven~icle
5 of the heart, and di~posed upon a lead wh.ch connects ~o the output of ~he
constant current source 11. The c~iclllator is arran~ed ~ produce pulses at
a frequency which js quite high compare~ to the hear~ rate! typically in
the range aE from S00 to 1000 Hz. A differential amplWer 14 h~ ita
invertlng inpu~ coupled via a conductor in the lead to $he elec~rode 12 and
10 i~ non-inverting input ~ ooupled by a separate conduct al~o conta~ned
wi~in the lead to the elecgrode 13. The output :from the dlfferenti~
amplifier 14, which is in the fm cE a modulated carrier wave, Is applied
to a high pass filter circuit 15 and from there, the output 15 f~d over a
conducta 16 to a half-wave rec~ifier network 17. The half-wave rectifi~r
15 provides its output to a low pass filter 1~ which removes the carrier signal
and from ~here, the envelope si~nal is applied ~hrou~h :~ur~her signal
proce~ln~ circui~y 19 to a voltage-~o-curren~ a~nYerter circ~ 20~ When .
troke vdume sen~ing ckcui~y heret~ore de~cribed Js ~o be used to
ccntrol ~e pacin~ rate of a cardiac pacer, the output from th~ clrcuit 20
20 may be oDuplad ~o tho ~iming circui~ portion ~ an implantable pulse
generatar 21 who~e output is QDupled t~ough a ~ her oonduc~ in the
lead to a s~imulating elec~ode 22 dispc~ied in or on the heart. llle signal
from ~he V-to-l conYerter 2a applied to the pulse gen~rato~'s timing ~< ,-
circuut may ~e ~oportional either to absalute ~troke vdume ~ to change
25 in ~troke volume, dependin~ upon the manner in which th~ output signal
from the low pass filter sta~e is processed.
Bef ae going into a detailed ~xplanation of an impl~men$aticn o:f
a circuit conforming to the block diagram of Fig,ure l, it may be help~ o
consider the de~ign of the lead str uct ~s which may ~o used ln
30 c~nbination with the preferred embodiment for effecting rate chan8e as
13~39~
a functial ~ the stroke Yolume parame~er of tho patient's heart~ In thls
regard, ~igure ~ illustrate~ one form Cf lead and electr~de ~hucture
which may be used. In this figure there is shown an endocardjal lead 23
having a tip electrode 2~ arranged ~ be dlsp~ed in the apex aE the right
ventricle and spaced proximally of this tip ~lectrode al~ng the axis af ~he 5
lead 23 are the conduc~ive rin~ el~ctrodes 1~ and 13 used far s~n~ing
variatials in impedance existing betwe~n them. It ha~ been ~ound that
during systde, as ~he cr ossffectional area ~ the hear~ decreases, a
corresponding increase is noted in th~ impedance exis~lng between the
senslng electrodes 12 and 13. 10
In Figure 3 there is shown an altern~lve lead oonfl~uratl ~n
wherein a single ring element identified generally by numeral 24 is slit
alcn~ a diameter so as to yield two generally cyllndrlcal ~ur~aces spaced
apart from one another radially, rather ehan axially, in forming the
electrode members 1~ and 13. 15
In the embodiments o~ both Figures 2 and 3, the l~ad comprises
an insulating sheath 23 surrounding three conductor~ 2S9 2~ and 27 which
respectively csuple the sensing electrod~s 12 and 13 and the ~timul~ting
tip elecb~ode 22 to the Implanted pulso generator. Th~ ele~rode~ 12 and
13 are di3posed on the ou~er surface o~ the In~ula~lv~ a~h 23 wh~r~ they 20
are exp~ed ~ body fluids wher, lmplan~ed.
With the two ring el~trode configuratia~ of Figure 2 th~ ~y3tem
may be rnodeled by a vdume conductcr af fixed l~ngth (the distanco
between the rir~g3 J2 and 13) and variable cros~-secti~nal area. Wi~ this
elec~od~ configuration, She cr 06s~ec~ion i3 perpl~ndicular to the 25
l~ngitudinal axis of the ri~ht ventricle in which the lead is adapted ~o be
ir~erted. Frorn the well-known fa~mula for c~rnputin~ electrical
resistance R ~ ~ ~ , it is apparent that a decrease in aos~-
~ ~3~3~
s~tianal ar~a (A~ which take~ place durlng systole will re~ult In a
corresponding increase ln the re~lstance mea~ured between the two
spaced electrodesO Likewise ~he increa~e in cros~-sectialal area as blood
fills the ventricles during diastde resul~3 ln a decrease in the re~l3tance
measured between the two spaced elctrodes.
In the split-ring electrode configLlration illustrated in Figure 3,
there is the advanta~e of increased sensitivity in tha~ both longitudinal
and radial motlon of the ven~icular wall resul~s in larger measured
impedance changes. A further advantage of the electrode ~nfiguration
10 af Fi~ure 3 is that it exhibits improved p~cer spike r~jection due to the
symm~tric positicning of the rings wi~h respect to the tip electrnde 22.
Offsetting these distinct advantages is the fact that the impedance
measurement obtained by the split-ring sensing electrode arrangement Is
dependent sornewhat on lead orientation. It can be shown tha~ the change
15 in impedance measurable using the split-ring electrodes decrease~ a~ a
co3ine function aP the an~le between the maximum wid~h dimension aE the
right ventricle and a line extending perpendicular ~o the axial gap
between the split-ring segments 12 and 13~
Figure 4 iUustrates a schematic elec~rical dia~ram of a circuit
20 arrangement implementing ~he system represented diagrammat~cally In
Fi~,ure 1. In this 3dlematic, the osciUatar la comprlse~ an astable
multivibra~or and b shown as being enclosed by the ~roken line box 28. It
includes an operatialal amplifler 29 whDse inverting Input terminal 30 is
ooupled through a capacitor 31 to a point c reference po~ential, such as
25 ~round, and wh~s~ ou~put terminal 32 is oDupled throu~11 a feedback
resistor 33 to ~he operational amplifier'~ invertinE~ input terminal 30. The
non-inYerting input of that ampiifjer is, in twn, coupled to a 3unct1~
pdnt 34 between series connected resis~ors 35 and 36, the remainin8
terminal c~ ~he resistor 35 being coupled ~o the output terminal 32 oE the
30 opera~ional amplifier and the rernaining ~erminal ~ ~he re~i~tor 31S belng
l3~3~
coupled to a point of reEerence potential VR. A resistor 37 is coupled
between the bias suppl!~ terminal of the operational amplifier 29 and
ground.
The output from the square wave oscillator lO is capacitivelv
coupled by a capacitor 37 to the constant current source 11 which is
illustrated as being enclosed bv the brokèn line box 38. The constant
current source 11 includes an operational amplifier 39 whose non-inverting
input is coupled through a resistor 40 to the source of reference potential,
YR, and a resistor 41 jolns the coupllng capaci~or 37 to a 3unctlon polnt 42
which is tied directly to the Inverting input of the operatlonal ampllfier
39. A bias resistor 43 is connected in a conventional fashion to the
operatlonal amplifier 39 and to a point of fixed reference potential
(ground~.
The output from the constant current source ll is coupled by one
of the conductors 25 in the lead 23 to a sensin~ electrode 13. The
remaining electrode 12 is coupled through a conductor 2S in the lead ~3 to
a terminal 27 which is tied directlY to the aforementioned terminal 42 oE
~he constant current operational ampliEier stage 39. As the heart in
which the lead 73 is implanted beats, changes in the volume of blood
present in the right ventricle changes and these changes are reflected as a
modulation of the output signal from the osclllator lO. The high frequency
slgnals from the oscillator may be considered as a carrier wave and the
wave is amplitude modulated by the impedance changes detected bv the
sensing leads and electrodes. The carrier may typicallv have a frequency
of lO00 Hz, but limitation to this frequency is not intended. It is found
that a carrier having a frequency of about lO00 Hz and an amplitude in the
1- to 1 0-microampere range does not produce unwanted tissue
stimulation. As such, the likelihood of inducing cardiac arrvthmias
(tachvcardia) is minimized.
The modulated carrier signal is fed to a differential amplifier
stage 14 ~shown enclosed bv broken line box 43a) which provides a
predetermined gain to the detected waveform. SpecificaIl!~, the signal
`~ ~3~39~
picked up on el~trode I2 i~ fed through a coupling capacl~or 4~ and a
re~istor ~5 to th~ inverting input c~ an operational amplifier 46. In a liko
fashlon~ the signal developed on the electrode 13 1~ ~oupled through a
c~upling capacitor 47 and a re~istor 48 ~o ~he non-inver~lng lnput a~ the
5 operatial31 amplifier 46. The non-inverting input is also oDupled through
a resistor 49 to the source ~ reference potential VR. A feedb~ck resis~or
50 join~ the output terminal Sl of the differential arnplifier sta~e 14 back
to the inverting input terminal a~ the operational amplifi~r 46.
The amplified modulated carrier signal from the differential
amplifier 46 is coupled to an active high pas~ ~ilter 6ta8e 15. The hi~h
pa!~ filter ~ta8e ls shown as beln~, enclooed by the broken llno box S3. it
includes a first operational amplifier 54 and a second operatlonal ~,
amplifier SS. ~apacit~ 52 applies the signal from th~ differ~ntial
amplifier 46~ via a further capaci~or 56, to the non-inverting input d tho .
operati~nal amplifier S4. The ~utput termlnal 57 of th~ operatlonal
amp~ifier S~ has a resistor 58 jQining it ~o ~he junct~on pdn~ between ~he
capacitor3 52 and S6. A bias re~istor S9 13 c~nnected at Qne tormlnal
dlrectly ~o the non-inverting Input cf the anpllfier stage S4 and at lt~
oth2r terminal to the source VR. A further resistor 60 is oormect~d
between ~ha~ same ~ource VR and the invertin~ lnput terminal 61 Qf ~he
operatia~al amplifier 54. A ~eedback resis~of 62 jains the outpu~ ~erminal
57 d that amplifier to ~he inverting input. That output i~ capaci~ively ,,
ooupled via c~ndensers ~3 and 64 ~o ~he non-lnvertlng input of the
operational amplifier 55. 1~ output terminal 6S ~ aoupled via ~eries r
conn~cted resisto~ 6~ and 67 to ~he reference sourCe VR and via r~sistor ;. ~:
68 to the junc~on punt between the serles conneGted capacitQrs 63 and
~4. The inverting lnpu~ ~f the second stage of the hlg,h pa5s ~ilter network
connects to the cammon terminal between ~he serles connected resistors
~6 an~ 67. .
The hi~h pass ~il ter stage 15 is a f aur-pole devlce whicil is
ef~ec~ive ~ pass $he modulated carrier signal~ However, the cwnmon-
m~de r~jectil aff aded by the dl~forential amplifi~r s~a~e 14 and th~ hl~,h
~3139~0
pass filter sta~e IS cooperate to significantly suppre~s eCG artlfact~ ~uch
as ~-waves ~r pacet sp~ke~ which may ~ picked up by the senslng
elec~rodes. Furthermcre,the high pass fJlter serves to remove ail other
artifacts, excepting the carrier signal which carries the Impedance
5 inf~matian in the fm of low frequency amplitude modulaticn thereof.
Shown enclcsed by the broken line box 69 is a half-wave rectifier
circuit 17. It comprises an operaticnal ampllfier 3taBe 70 havln~ lts
Inver~ing input oDupled through a re~lstor 71 to the output Junctlon ~S ~
the high pass filter stage IS. The non-inverting input of the ampllfier 70
10 i~ aDupled through a resistor 72 to the reference source Vf;~A flrst di~de
has its cathode connected to the output terminal 73 of the operatl~
ampllfier 70 and its ar~de terminal connected to the invertin~ Inpu~ oE
~hat amplifier. A series circui~ indudin~ a further dio~ 7~ and a parallel
cornbination af a resistor 76 and ~ capautor 77 is coupled between that
same output terminal 73 and the inverting input o~ the operatl cnal
amplifier 70. With the diodes 74 and 7S pded a~ ~hown, only po~ltlve
excur31a~ of ~he m~ulated carrl~ are reproduced at the output terfninal
7Sa.
Fdlo~:vlng rectificatial, the resultin~ si~nal i3 appllod to a thre~
pde low pa~9 filter Circuit 18 which is shown In Flgure 4 a~ b~lng on~ a~ed
by the brokm line ~x 78. Thi~ ilter Includes an op~ratianal
amplifier 79 having ~ non-inverting input terminal ~û, an lnv~tlng lnput
terminal ~1 and an output ~errninal 82. The output termlllal 75a of the
half-wave rectifier is ooupled ~hrough a series ~ing dE resl~tors B3, 84
and 8S t~ the non-lnverting input terminal 80. A capacltor 86 couples
tha~ sarne Input terminal to a source cf reference potentlal VR. ~ further
capacltcr 87 is ~upled b~ween ground and the j~cticn polnt between
the series connected re~istors 83 and 84. A Eeedback re~istor ~8 joins the
output terminal ~2 of the operaticnal ampllfier 79 back to it~ Jnvertin~
input terminal 81. Tt~ ~ame Inverting input terminal 81 i3 ~upled
t~ough a re~i~tor ~9 to th~ Yolt~e ~ ce VR. A feRdback capacltar 90
~3~3~
connects between the output terminal 8~ of the operati~al ampll~ier 79
and the junction ~ormed between ~he series connectcd r~istor~ B4 and $S.
The component values oi ~he ls~v pass filter circui~ are chosen
~uch that lt exhibi~ an upper cut-o~f frequency ~ about S ~5z. As such,
the la~ pass filter stage 18 is effective to strip away the carrier ~ignal7
leaving only the envelope wavefos rn. This envelop~ waveform is found to
bear a clc~e resemblance to the publishecl stroke volume wavef ~m~
reported by Geddes et al, supra.
The dem~ulated envelope signal is applied through addltiDnal
signal processing sta~es sh~wn enclssed by ~roken line ~x 90a 30 that It
may ul~lmateiy be used to perf am a controlling functial on a utllizatlcn
device, sueh as to modify the timing circui~ cE a cardiac pacer pulse
gener~tor in a fashlcn to Yary the rate at which stimulating puises are
generated as a function cf mea~urecJ stroke v~umè. This further ~Ignal
proce~jing circui~y indudes a DC restorer network indicated ~enera~y by
numeral 91 and a further low pass filter s~age indicated senerally by
numeral ~2~ The DC restorer includes an operatianal amplifi~ 93 wl~
inverting input is coupled through a capacitor 94 and a re~ or ~s to the
o~stpu~ fram the l~v pass fil~er L8.
The re~istor 9~ comprises a portian of a voltage divider whlch
also lncludes a resistor 96~ that latter r~sist~ being connec~ed b~tween
gro~ d and the common ~erminal between the capacitor 94 and th
resistor 95. A further v 21tage divider including fixed resls~ors 97 and ~8
and a potentlcaneter 9g is coupled between ground and a source of
regulated Ydta~e, VREG. llle wiper arm d the p~entl~n~ter 99 Is ~ed
dir~ctly to the non-invcrtlng lnput of the operaticnal ampllfier 93. A
clamping diode 130, pded a3 indicated, is connectecl b~ween the output o~
the operaticnal amplifier 93 and ~he junctian polnt between tho ~erie~
connec~ed resistors ~S ancl ~6. The l)C re~torer circui~ 91 cause~ the
voltage signal deYeloped at the output of the law pasS filter l8 ta b~
clamped ~0 a Ydtage established by ~he settin~ clE the potentiwneter 99.
~ 3~3~
The output ~rom the DC re~torcr clrcul t Is connQcted via
condustor 101 to the further low pass ~ilter s~age 92. Thi3 low p~9 fUt~r
is designed to exhlbit ~wo poles and includes an operati~3al amplifier 102.
The non-inver~in~ input Q~ amplifi~ 102 receives the ou~put from the DC
restorer stage via serie3 cormected resistors 103 and 104. A feedback
capacitcr 106a is connected be~ween the output ~erminal 105 cdE the
operaticnal amplifier 102 and the ~omm~n jun~ial between the series
connected resistors 103 and 104. A further capacitor 106 is connected
directly between the non-inverting inpu~ terrninal ard the refer~nce
vdtage source VR. A vdtage clivider including resistors 107 and 108 is
connected in series between the source VR and ~he ou~put ~erminal IOS of
the low pass filter operational amplifier 102. The inverting input ~f that
amplifier is tied directly to the junction poing be~ween the series
connected resistors 107 and lQ8. The signal processing circui~y f dlowing
the final l~w ~ss filt~r sta~e 92 may t~ke one of two f crms. In the view
of Figure 4, the circui~y is arranged ~o create a cu~rent amplitude which
is proporticnal to ~n abs~lute reference stroke volume, th~ reference
being es:tablished by the settine~ ~ the p~tentianeter 99. By substituting
the circui~y shown in Figure 5 f ~ that f dt owing the junctian ~abeled "X"
in Fi~ure 4, a curren~ signal is produced which is p~oportional ~o changes
in stroke volume and ha~ no relative reference.
With the for~go~ng in mind, ~hen, consideration will continue to
be given to the embodiment illustrated in Fi~ure 4, i.e., the arrangment
which ylelds an ab~dute reference stroke vdurn~ c~rent ~ignal. The
out,out from the l~v pa~ il~er stage 92 is o~upled through a resist~ 109
to the inverting input cf an operational amplifier 110 who6e non-inver ting
input is coupled to a voltage reference s~urce YE~, by means of a resistor
111. An integra~ing capaci~a 112 is conne~ted as a feedback element
be~ween the output terminal 113 o:E ~he operatianal amplifier 11~ and its
inverting input terrninal. The inte~rator circuit just ~escrilbed functions
12
~o integrate the difference between She actual s~roke volurne as
represensed by ~he envelope ~ the modulated carrier signal and the
reference potential set by the p~ten~iane~er 99~
The output frorn the in~egrator is applied to a vdtage~~o-cwrrent
5 converter circuit 114. This circui~ includes an op~ratia~al amplifier llS
having its inverting input coupled through a variable resistor 116 to the
output from the integrator stage. The non-inverting input of the
operational amplifier 115 is ~oupled through a resistor 117 to the reference
voltage source VR. Connected as a feedback element on the vol~age-to-
current converter 114 is a NPN transistor 118. Speclfically, the base
electrode of that transistor is coupled to the output of the operational
amplifier 115 and its emi~ter elec~rode ls tied to ~he invertlng input. The
resulting current signal lo~,t flowing in the collec~or circui~ of the
transis~or 118 may be represented mathematically as f dlows:
I c~ r ~v ~IPot 99 3 - VR
c~ut ~
where Vsv is the ampli~ude of the s~roke volume at the
output af the DC restorer point 101.
This current signal is fed to a s~called current mirror network
11~ which functions t~ ~,enerate an owtpu~ currenS which 1~ equal to the
ne~ative of the lnput current. The mirror network include3 fir~t and
second PNP transistors 120 and 121 whc~e emitters are tled in cornmon to a
regulated voltage source VReg and whose base electrodes are tied in
ccmmon to the cdlector electrode aE ~he transistor 118. The cdlector o~
the transistor 120 is also tied to the oollector electrode of the transistor
118 while the ou~put signal from the current mirror 119 is obtained at the
collect~ el~trode of the transistor 121 throu~h coupling resistor 122.
In sne application af the invention, the output from the current
mirror circuit 11~ may be applied ~o the timing circuit of a cardiac pacer
pulse generatc~ însuch a way that the normal pacing rate o~ ~hat pulse
~3~3~
generator is made to cleviate frorn a preset rate as a functlon of the
cu~rent injected into that timin8 cireuit. A ~ypical, prior art, R-wave
1nhibited demand pacemaker wi~ which the present inventicn may be
used is fully described in the Anderson et al Patent 4~041,953. With
re~erence to that pator~t, ~h2 curren~ obtalned a~ tho output termln~l 123
ct the pre~enS inYention would ~ connected to the cornrnon pdnt be~ween
the collector electrode of transis~or Q103 and ~he timing capacltor C::101 in
the pacer circuit Illus~rated in Fl~ue 6a aE the Anderson et al Patent
4,041,953. In this way, the curren~ signal contribul:ed by ~he stroke
valume sensing appar~tus aE ~he present Invention may be lnjected lnto
the timing capacit so as to effect a variation in the rate in which pacer
pulses are generated in the absence of normal R-wave activlty.
OPERATION - F:1GURE 4
Now that the details d the cvns1ruction af a first embodirnent
of the present inven~i~n has been set out, consideratian wlll be giYen to
1~ node oE operation. In this regard, the w~veform~ ~et forth In Figure~l
6a ti~rou~h 6i are believed to be helpful ~o a full and o~mple~e
under~tandin$ cE the operatlon. As has a~ready be~n Indlcated, the
embodiment of Figure 4 is designed eo provide an ab~ e refe ence
stroke vdume, the reference being set by the poeentiometer g9.
Furtherme, the control current is assumed to be injec~ed into the timin~
circuit cf a pacer. This current is in3ected until such l;lrne a~ the
integrator capacitar 112 is fully discharged. This does not occur until the
stroke volwne has returned to or fallen below the pre~et roferenc~ value.
Figuro 6a illustrates the si~nal wavef~m obtained at the output
terminal 32 aE the o~cillator circuig 10 which signal b applled to ~he
sensing electrocies 12 and ~3 disposed or~ the surface of a lead which i5
designed DD be placed in ~he right ven~icle af ~hr heart. As the hearlt
beats and bl~od enter~ and leaves ~he righ~ ventricle, a ~hang,e In
14
` ~313~3
el~trlcal Imped~nce between the sensing electrodes 12 anl 13 ~k~ place.
Thij impeJance change results in amplltude modulatlon Pf the 03clllator
output sl~nal and that ma~lulated signal is applled across the Inputs of tho
di~ferentjal ampli~ier s~age 14. Waveform ~b Illu~trates the si~nal
5 appea;ring at the output of the differe~ial amplifier. Here, the leC~;
waveform is superimpcoed on the carrier signal such tha~ ~he ~troke
volume modulaticn is somewhat difficult to observe at ~his point.
Waveform ~c is illustra~ive a~ the waveform observed at ~he
output of the hi8h pass filter network 15, i.e., a~ the output terminal 65 of
10 the operational ampllfi~r S5. In passing through the high p~s~ fllter, ~h~
ECS:~ wave 15 removed sL~h that the stroke volume modulatla~ o~ the
~;cillator outpu~ ~carrier ~ignal~ 1~ now quute evident.
Wavef ~m 6d represents the output from the half-wave rectifier
17. As is indicated, the h~lf-wave rectlIier serv~ to remove the nega~ve
15 ~ing peaks from the modulated carri~r.
When th~ hal~ wave rectified ~troke volume modul~ted carrler
signal is next applied to a losv pass ~ er as at 18, ~he waveform
represented by Figure 6e i3 representative of what would typically be
observed at the output terminal 82. This o~put constitute~ a vdtage
20 which ls proportlcnal to the In~iitantaneou~ ~troke v~lume. ~ter pa~3in8
through ehe clamping circuit 91, ~he waveform o~ ~igure 6f ropre~n~ the
lnstantaneous strolce volume signal clamped to the voliage VR.
The waveform aE Figure 6g illustrate~ the damp O~ltpUt
appearing on oDndu~or 101 a~ly with a lcnger time scale. It show~ an
25 increase in strol~e vclume fdlowed by a decrea~e. When this ~i~nal is
applied to the secQnd low pas~ fil~ age 92, the wavef ~rm illu~rated In
PJ~ure 6h appear~ at the output terminal 105 d tha~ low paS~ ~llter. The
ciamp fcr the previ~s s~age i~ adjusted to give a i:)C output :~rom ~he l~w
pa~s fJlter af a leYel VR when the ~roke v olum~ h~ the de~ired
30 ~mplitude.
:13:L3~
As is illustrated in Figure 4, this signal is applied to the
inte~rator circuit 110 and the ou~put Qf the integrator is represented by
the wavef crm of Figur~ 6i. Here, the output is the integrated voltag*
excursion cf the si~nal frorn the VR level and may b~ represented by th~
5 equaticsl set out on page 13, supra. This vol~age ~ignal i~ ~nvcrted to a
current signal by th~ vdtage-to-current converter clrcult 114 which
produc~s an output current ~qual ~o the input voltago minus ~hc refer~nce
vdta~e dlvid~d by ~he resistance cE the variabl2 r~ tor 116. Accordlngly,
the output current ~rom the ~ltage-to-current convorter m~y be
r epresented by the equa~on set out on page 13 heresJE. 1~ 15 this current
that may be coupled through the mirror clrcuit 119 ~o the timing circuit of
the demand pacer pulse generator or to a contrd paint in other medical
electronic apparatus which may broadly be con~ider~d as a oontrolled
d~vice~
It will be fcund th2t when physidogic demand creates an
increase in ~oke vdume, the current injected into the timlng clrcuit c~
the cardiac pacer will decrease the timlng perlod of the puls~ generator
whereby artlficial ~timLIlatlng pul~es wUl be produced at an ln~ea~ed
rate. A~ already b~n menti~ned, when the heart r~te Increase~, a
cDrresponding decrease in ~troke vdume results. Thus~ the circw~ alE
Figure 4, when properly connected to a cardiac pacer pulse ~enerat~
having a current sensitive timin8 circuit as in the circuit c~E the
afaereferenced Anderson et al Patent, will cause that pulse 8enerator to
operate at a stimulatlng frequency which varies in accordanc~ wlth the
deviatia~ of th~ measured stroke v~lume from a pre~et lev~l. When the
stroke vdumo increa~es, so does the pacing rate. Increa~e~ in pacing ra~o
result in a oorresponding decrease in stroke volume. Hence, the circuit
op~rate~ to maintain stroke vdume relatively corlstant at a
predet~mined threshDld level.
The clrcuit of Fi~ure 4 may be ma~}fied ~o that ln~tead of
continuDusly operating so as to force ~he stroke volume signal towar~s a
preset rof~ence, the system will in~tead be ~ensitive only to ch2nge~ ln
16
~3~3~
stroke Yolume without respect to a rel~ive reference, Here, the
ventricular pacing rate is made to vary ss) as to minimi~e changes in
stroke volume. In implementing this al~erna~ive arrangement, ~he portial
aE the circL~i~y shown in ~:igure 4 to ~he right a~ the polnt labeled "X" is
5 replaced with ~he circui~y sl~wn In ~igure S. Speci~ic311y, the output
frcYn the low pass filter ~ta~,e 92 is arranged ~ be ooupled t~rou~h a
resistor 124 to ~he non-inverting input of an operatianal amplliEier 12S. A
feedback resistor 126 is connected betwe~n the operatIonal amplifier's
output terminal and its invertin~ input terminal. A furthsr resistor 127
10 has one terminal also connected to ~he Inverting Input termlnal ~E the
amplifier 125 and its remaining terminal connected to the reference
vd~a~e source Y~. lhe function cf the non-inverting ampllfler stage i~ to
introduce a predetermined gain to the vol~age ou~put iErom the law pass
filter sta~e 92. Typically~ this gain may be a ~actor cf 10.
The amplified signal appearing at ~he output of ~he operatia~al
amp~ifier 12~ i~ next applied as an input to a current contrdler c~cuit
whlch is in~ica~ed ~enerally by numeral 128. It includes as l~s active
elements a f~ther opera~ional amplifier 129, a firs~ tran~ist~ 130 and a
second transistor 131. ~he output frorn the non-inverting amplifier 125 is
coupled through a relatively large capacitor 132 to the non-inverting Input
of the operaticnal amplifler 129. A further cormectl~ i n ade to ~h~
non-invertin~ input from the cenlter pdnt on a valtage divid~r network
compri3ed of !lerles Q~nnected re~i$tor~ 133 and 134. Thi~ serl~ r~slstance
arrangement is conne~ed between a souuce aE regu~ated vdta~,o VReB
2 5 and ground, The inverting input to ~he operati anal amplifier 129 is
coupled through a varlable resistor 13S to th~ reference v~tage source
VR. Resistor 13S ls made variable sothat the
~ ~, lthe change in output current per urut)
a~Jsy (the change in stroke volume amplitude in vol~s)
17
```` ~3~3~
can be adjusted. ï'he transist~ 130 is connected as a feedback element,
havin~ its base elec~rode coupled to the output ~ the operational
amplifier 129 and its emitt~r electrode connected to the inverting input of
that same amplifier. The cdlector electrode ~ the transistcr 130 is
connected by a conductcr 136 to a current mirror circuit 137O The
~ransist~ 131 als~ has its b~se electrode ~upled to the output a the
operatiQnal ampll:Eier 129 and it~ collector electrode 1~ aonnected dlrectly
~o the non-inverting input a~ that arnplifier. The tran3i~tor 131 15 blased
by means of a potentiometer 138 which is o~uple~ be~ween the volta~e
10 source VReg and VR~ the emitter electrode ~ the transistor 131 bein8 tied
tothe wiper arm of that potenticsneter~
The current mirror circuit is substantially ldentical in
cons~uc~ion to the curren~ mirror circ ~it 119 ~ Fi~ure ~ and includes iEirst
and second PNP transistors 139 and 140. The base el~trod~ of these two
15 transistors are tied in cornmon with ~he callector electrode ~ the
transls~or 140 and to ~he collec~ elecirocle of the ~ransis~or 13D by way
a~ conduct~ 136. The emitter electrode ~ the transistors 139 and 140 are
tied to~ether and to the regula~ed voltase saJrce VRe8. ~he output :from
the current mirror circult is fed through a resistor 1~1 to an ou~put pdnt
20 labeled 142. It is this output point which is arranged ~o be ~nnected to
the timing cirCuit d the pacer pulse generator as has alr~ady been set out
in detail when the circuit arrangement of Fi~ure 4 wa3 under discussia~.
It will be recalled that the output si~nal appearing at pdnt "X"
in Figure 4 is a voltage propor~ al to s~roke volume. Thl~ voltage i~
25 amplified by the non-inverting amplifier 125 and the re~ ing output Is
f~the~ cessed by the current o~ntroller circuit 1~8 in such a fa~hia~
that only change~ in the strok¢ vdume ~re c~ signific~nce. The chan~es
in stroke Yolume, of course, ~re dependen~ u~pn the phy~i dogic demand of
the b~dy.
3 ~
The capacit~r 132, in o~mbinati on with the remainder of the
circuit, provides a very lar~e time constan~, the capacitor actlng as a
differentiator. Stated otherwise, it comprises a hiEsh pass filter with an
extremely lsng tirne constant. The time constant is de~ermined by the
5 value of the capacitca 132 in microfarads mul~iplied by ~he effective
resistance o~ resis~or~ 133 and 134 measured in megohms. This time
constant may be set to be approximately In the ran8e from ~lve to thlrty-
five minutes, 10 minutes beinK perhaps typical Under steady-s~ate
conditions, the voltag~ appearing at ~he non-inverting inpu~ of the
10 amplifier 12~ wiil be determined by the magnitude aE the 13C vdtage
obtained at the jlmctlan point between the resistors 133 and 134. The
capacit~ 132 will allow only changes in the signal output fran the
amplifier 125 to pass. The cs~mponent values are selected such that up~n
occurrence af chan~es in the stroke vdume vdtage signal, approximately
15 thirty minutes, i.e., approximately thr~e time constants, are required ~
the current si~nal observed in conductor.l36 to return to its qu~oscen~ or
steady-state level. This thirty minute period corresponds quite closely to
that which matches hurnan phyudo~ical requirements. That is to 5ay9
f dlowin~ significant exercise, approximately tw~n~y to ~hir~y minutes are
20 required for the heart rate to re~urn ~o the at-rest rate.
The control signal which is developed at the non-inverting lnput
aE the operational amplifier 129 is the actual contrd signal which is, at
this point, a functicn of the changes in stroke volume, not the absolu~e
value af the stroke vdume measurement. The amplifier 129 is desi~ned to
25 conve~t that control slgnal into a current which may be injected inso a
conventional cardiac pacer pulse generator in such a fashion tha~ the rate
~t which ventricular stimulating pulses are generated will be adjusted as a
function oE that con~rd signal which may be applled to ather ~pparatu~
where s~roke ~lume monitaing andJar response to chang~s in st~oke
30 vdume is desircd.
19
`` 13~.3~
Referrin~ manentarlly to ~i~ure 6a of the Anderson et al Patent
4,0~1,953, the translstors Q101 and Q10~, along wlth ~he r~sistor~ R103 ~nd
R104, comprise a constant current generator~ That current s~rce s~ts up
a vdtage, then, that aJlows a curren~ through ~ransistor Q103 for char~ing
up the pulse generator's ~iming capacitor C101. That las~-menticned
capacitar forms a portlon a~ the E2.C: ~ime cons~an~ d the oscilla~or
portia~ of the pacer pulse generator. By injecting current at the poin~
indi at~d, $he char~in~ time cE the capacitor C101 is decreased and ~he
ventricular stimulating pulses appearing across ~he Hear~ ~ and Hear~-
terminals ~ the pUl~R generator circult wlll Increas~, as~umlng that
naturally occurring R-waves do not inhibit ~he ope-atian of that demand
paCer.
Summarizing, m ~nentarily, the circuit of Figure S, when coupled
to the tie pcin~ "X" jn Figure 4 and wed as a rep~acement for the
circui~y in Figure 4 loc~ted downstream from that tie~ point, provlcle8 an
injected current which is proportional to changes in ~troke vdume. Only
increase~ in ~roke volume are sensed. Decrease~ in strok~ volume result
in the discharge c~E ~he capaci~or 132 which, as i~ dischar~e~, d~crea~e3 the
injected current level.
With no llmitatial intended and f~ illustr~tiw purpo~es only,
the f ~l~wing table sets forth typical component values which m~y be used
in implementing the str~k~ volume sensing and pacer control apparatus o~
th~ pre~ent inYenl'tion.
13~3~
T~BLE ONE
CO~PONENT ~fALlJES
RESIST~S VAI,UE CAPACIT~RS VALUe
67,71 76,88,~9, 200 p~
124 127 141 1 M 37 0,56 uf
3.3 M 44,47 0.1 uf
36 1.4 M 52,56,63,64 0.001 uf
10 40 ~ K 77 5 pf
41 100 K 86,87 0.033 uf
43,49,S0,59a, 94 10 uf
72a,10g,111,126 10 M 106,106a,112 4.7 uf
50a 5 M 132 25 u:E
15 58,59 78 K
S6 1.8 M
66a,68 150 K OP AMPS TYP~
68a,103,104 3 M 29,39,46954,S5, ~ATIONAL LM 42S~
7~J117 500 K 70p79,g3,1029 INT~RSIL ICL 8023
20 83 50 K
84,85 910 K
8~aj96,1Q8a, ~ TYPE
133,133a 22 M 118,130 2 N 2484
2 M 120,121,131,
97,98 4.7 M 139,140 2 N 3799
99,135 I M Var.
116 2 M Yar. VOLTAGES TYP~
. . _
134 12 M V~ 0.~7S V
138 5 M Var. VReg 1.75 Y
~ ~313~
The invention has been described herein in considerable detail, in
order to comply with the Pa~ent Statutes anJ to provlde those skilled in
the art with information needed to apply thc novel principles and to
construct and use such specialized components as are required. However,
it is ~o be understood that ~he invention can be carried out by specifically S
dif~erent equipment and devices. For s~xampl~ the control current
proportlonal to ~$roke volume change may be used in cor.jlmotion with an
implantable infusion pump for administering such drugs as dobutamine
isoprotorenol or nitroprusside whereby stroke volume may be maintained
at a desired value. Alternatively9 the demodulated waveform or control 10
signal may be used directly by other diagno~ tic equipmen~. By
appropriately utilizin~ the information derived from the ventricular
impedance, it would be possible to measure stroke volume without having
~o resort to thermal dilution or other techniques. Hence9 ~arious
modifications, both as to equipment details and operating procedures can 15
be effected without departing from the scope of the invention It~elf,
What is claimed is:
