CA1199371A - Ultrasonic enhancement of cardiac contractility synchronised with ecg event or defibrillation pulse - Google Patents

Abstract

TITLE
METHOD AND DEVICE FOR ENHANCEMENT OF CARDIAC CONTRACTILITY

INVENTORS
George V. Forester Alan J. Mortimer Orest Z. Roy ABSTRACT OF THE DISCLOSURE.
An apparatus for ultrasonic irradiation of the heart either when the chest is open after surgery or through the chest wall. It may also be used in conjunction with electrical defibrillation equipment or alone. The apparatus includes an EKG for detecting the heart beat, an ultrasonic generator and timing and pulsing circuits for providing timed pulses of ultrasound to coincide with selected events in the cardiac cycle.

Description

Thls invention relates to prodllcl.ng an enhancelilent of cardlac contractili.ty throllgh the use of ultrcl.sourld.
More partlcularly, the presen~ LnvelltLoll provi(les a method of improving cardlac performallce by appLying ultra.so~ d to the heart Ltself, either ~nternal.ly from ~q catlleter plflce(l wit.llin tlle heart, by ultrasoundIrradiatiorl appl:Led orl tlle surface of the bocly, or by ultra.qourlcl irradla~
tion applied directly ln contact with the heart. Ultrasourld -Ls also applied in combination w:ith an electrical deEibril.lator or pacemakerO
~le tnvention also relates to a metllod for application of ultrasound for well defined and selectable periods o~ time arranged to colnci.de wlth critical events in the cardiac cycle~
In addition, the lnvention relates to a method ~or the applica-tion of ultrasound ~or weLl defined and selectab].e periods of time relat-ed to critical events in the process of electrical def.LbrillationO
When the ultrasolllld waves produced by the transducers are a~justed such that their energy traverses the heart Ltself, the action of the waves can exert their e~fect by creating microthermal heating, micro-circnlation changes, stirring, stab:Le cav.Ltat-lon, microstreami.ng, or chemical effects~ The differential heating i.s produced because of the knowll property of ultrasound to be ab.sorbed by tissues according to their viscosities. Thus, membrane organelles within the heart absorb more energy than cytoplasmic components. It is thus expected that the sarco-plasmic reti.culum belng an internally located organelle within the heart would absorb energy and be heated preferentially before cytopla.sm.
Similarly, the sarcolemllla and its internal projections - the transverse and longitudinal transverse system would also be heated more thall extra-ceilulAr areas and cytoplasm. ~ecause of the differential heating, one woul.d expect bLo].ogic actLvitLes associated with these membranous compon-ents to be stimulated.
Thus, we find a linear relatlonsllip between myocardial enhance-ment between ().2 watt/cm2 an(l 2.() W/cm2 SAT~ of ultrasound exposllre~
This implies that when energy from ultra~soulld is applied wlthin a range to increase diEferential heatillg wltllin the l-Lmits commensllrate wlth bio--loglc activity (<44C~ we call fiel.ectlvely improve myocardla:l. performance.
~ur experimelltal evidence fihows that a portlon o~ the ~ILtrasoulld e~ect 3~

is produced via an increase o~ thc e~f-Lclellcy oE the excLtat-Lon-colltrac-tion coupling ~ystem. ~econd'ly, ~he actlorl poten~lal of ultrasound irradLated cells indLcates an imE)rovemellt in calcium transfer across the membrane in the ylateau phase. Both of these Eacts suggest that ultra-sound modLfies ~arcolemmal (external muscle membrane) characterir;tlc6.
The ultrasolllld eFfects are complete1y reverslble as opposed to conven-tional drug therapies.
Tl1e changes irl the "act~on potent-Lal" characteristics are con-si~stent wLth tlle view that membrane properties and, hence, biologlc prop-1~) erties are temporarily modlEied by ultrasound. Such changes would alterthe sodium-potassium ATPase~ This is seen in the resting nonexcited heart muscle as a rapid hyperpo]arisatLon of the membrarle potential which can be interpreted as an Lncrease in the activity of the Na~-K~~ATPase of sarcolemma. Seconclly, the rapid increase in the overshoot of the car-diac "action potential" with ultrasound point6 to an alteration in mem-brane permeabiLlty with ultrasound during membrane excitahility. Caf-feine at 2.5-3,5 mM/L will block the ultrasound eEfect showing that the sarcoplasmic reticl~lum is an lntegral part oE the expression of the ultrasound enhancement. With caffeine and hypernatremia, we obtain an increase in diastolic tenslon rather than a decrease. This a]so shows that ~he sarcoplasmic reticulum is 1mplicated in the expression of the ultrasound effect. The ultrasonic production of myocardial enhancement can be produced through a number of modes. It is most rapid with contin-uous wave ultrasound but it may also be produced with improved efficiency

2~ but at a sligllt loss in rapidity with pulsed ultrasound. Thus ultrasound pulsed in conjunction with an E~G sLgnal througll an appropriate circuit can aLso limit whole heart heatlng but produce the differential heatlng in the most advantageous portlon of the cardiac cycle to enhance the con-tractile behaviour of the heartO Pulsed, continoous wave, or a combina-tion of both, may be used in an predetermined or spontaneous mode toirradiate the lleart accordln~ to the c'Linic.1l conditLon nf the patient.
Mode of Appllcation Application in closed chest mode (extrathoralc applicat:Lon):
In such a case as where a patient e~hlbits cardiac Eailu-re and has a ventricll1ar tachycar<11a or ventrLculclr ELI)ri1'LatLon; u'Ltrasourld may ~e appl~ed by usin~ in the ~-Lrst instarlce, a trans~l1cer aimed at the heart and placed between the 4th and 5th r~bfi to the reglon o~ the heart~
Tl1e transducer i9 lleld firmly in place ag.~1llfit the chest and tran61nlssLon is alded withlr1 fl suitable couplillg mechallism. Tlle ultraso~nd Irradia-tion is either applle(l continuously or tLmed tr) the EKG slgnal via thecouE~ling clrc~lit. In this way, ultrasoun(l reaching the heart can effect the changes descrLbed in this app11cattor1~
In tlle case oE a fibrilLat~ng l~eart, the uLtrasoun(l may be applied throngh a transducer as above9 prlor ~o defibrlllation or may be applied as an integral part of the deftbrillatLng electronics as describ-ed in this application. The applicat~on of ultrasound preceding the defibrillation charge ~s ~sually as a cont~nuous wave. 11owever~ ~he con-trol circuit wi1l apply ultrasollnd in a pulsed mode as soon as an ~KG
slgnal is generated. ~1U~ tl1e ultrasotln~1 may be applied be~ore~ during and a~ter the defibrillation in order to enhance the recovery of the myocardium~
In the case where a pacemaker is used to program a heart beat cycle and inserted temporarily or permanently into a patient, the extrathoraic applicatton of ultrasounc1 may ~e used to augment the performance of a weakened heart. Preferably, ultrasound ptslses are ti~ed to coincide with a selected event ln the programmed beat cycle.
Open Chest Appllcation:
Where the heart of a patient is exposed due to a surgical intervention, such as in open heart surgery, the ultrasound may be applied by a transducer or transducers directly to the heart with a su-lt-able coupling medtum. This would be especially useful following open heart surgery where the clrculatLon of the blood and perfuslon of the body has been performed by mechanlcal means and must be transferred to the heart itself. The heart belng Ln a weakened condition from the period of anoxia and trauma, it cannot immediately perform the work necessary to sustain the circulatiol1 and may ultimately fai1. The use of ultrasound to augment cardiac performal1ce will result in a qulcker and more sustained recovery from the intra~operatLve state~
In the case where the heart wtll not resume its beat with or without paclng al1d reverts to random electrica1 ar1(1 mechanlcal actlvity (Elhrillat~oll) or ~a~l1ycard~a, ~he lI'`t` 0~ ul~:r;lsolll1(1 wLtl1 or wlthout tlle defibrillatory shock~, ~s shown in th~ apF-l1.c.1tion, wLll induce rhythmi-cal electrLcal mechanical activity, decre~sing the time to recover frorn tllis potentially catastrophic event(s).
In the case ~There a pat:Lent's heart can be weaned succesæfully froTn a mechanical pumplng device (heart-Lung machlne), the application of ltrasound directly to the heart ns de.~crLbed ln tni.s invention w:Lll assiLst in Lhe recovery ~hase of the immed1.ate post-operative cvndition.
In tl1e case where ultrasound wollld have to be applied by a Tniniature transducer to the heart, inserted via A catheter to the left or rigllt myocardium in a vein or artery, tl1e ultrasound probe may be insert-ed quickly if a patient i.n a critical state requires cardiac enhancement, such as in case of shock, Low volume syndrome (hemorrhage), nervous sys~
tem damage, brain damage or malFunc~ion, myocardiaL ischemi~, angina attack6. This may be applied in hospita1 or in an emergency vehicle, or in the fleld. Furthermore, the device can be used as a tool in the study of the :Eunctioning o~ the l1eart as an lnvestigative instrument.
Ultrasound must be applied to the heart in order to effect an improvement in the cardiac performance. The present invel1tion provides methods of applylng ultrasoulld having a frequency greater than 20 K11z and 2() up to 25 MH7. cluring critical periods of the cardiac cycle, without damage to Lntervening tissue or ~he l1eart itself in order to i~1prove cardiac contractility.
Accordingly, tl1e present invention provides an apparatus for ultrasonic enhancelTlent of cardiac contractility, said apparatus co~pris-ing means for detecti.ng a heart beat, means for generating ultra.soul1d,ancl ~eans for providlng timed pulses of ~sai.d ultrasoni.c energy, each said pulse to coincide witn a selected event in the cardiac cycle.
Brief Descriptlon oF tlle Drawlngs Figure 1 is a diagrammatlc iLlustratlol1 of the ultrasontc car~

3() diac contracti:lity enhancirlg apparatus of this invention as it ~ould appear 11l use durLng he.lrt surgery.
Figure 2 i~ a sectlonal side elevat:Lonal. vlew of tl1e ultrasonlc transducer oF ~igure 1.
Figure 3 i~s a bottom plan vi.ew of all ultrs1~30~:1.c tra11sducer com ~)ined with an elee~trlc deFi.bri11ator.

Figure 4 Ls a cross-sectLonal .sl(le elevcl~orlal vle~ of the transdllcer of figure 3 taken alon~ l:he II.ne 4--l~ of fiKure 3.
Figure 5 is a schr.~natic draw:lng of tlle electrical controL clr-cuit oE the ernbo(limellt of ~igures l.'àn(l 2.
5Fig~lre 6 is a schem.ltlc drawing oE the control cLrcuit for the emboriiment of ~iKures 3 and 4.
Figure 7 is an illu.stration of tlle s-lgllal forms at dlfferent poLnts in the circuitry of flgure 5.
Figure 8 ls an illustrat:Lon of the sLgnal forms at diEferent points in the circuitry of figure 6.
Detailed Description Referri.ng now in detai'L to the drawings, the ultrasonic cardiac enhancer apparatus shown generally at 1() ill f:Lgure 1, :Eor use in intra-operative applicatLon, includes a transducer assembly, shown at 12. The ultrasoulld i.s produced by a pie7.0electric rnaterial or other means 14 mounted i.n a housing 16 of sui~able pLasti.c material. Tlle :i-'ront face of the houslng 16 ~as a menlbrane or cover 18 of material, such as latex rub-ber, to provide maximum transmission of ultrasound to the water coupling medium 2Q surrounding the transducer 12. l'he transducer 12 is centered in the transducer llousing 16 by ~eans of a transducer centering device 22 so that the ul~rasound energy exi~s frorn the transducer housing 16 in an unimpeded manner. The ultrasound leave.s the transducer housing 1 through an acoustic window 24 which provi.des very little disruption in tlle ultrasound beam. To maintaLn the transducer housing 16 and, particu-larly portions o~ the transducer housirlg 16 in contact with the patlentat body temperature, heatLng/cooling coils 28 are placed in the ~ater coupling mechanlsm surrounding the transducer.
The ultrasound irradiator used for closed chest application of ultrasound contains all the features descrLbed previously. In addition, a focussing e'lement 3~ of lucite (TM) or other ~u:Ltable material, Ls placed in front o~ the trans(lllcer 12 to focu~ the Illtrasound to a po:Lnt within the water batl~ coupli.llg medium ad~acerlt to the acoustlc w:Lndow 24.
This feature provides a narrow beam to pas.s tllrougll solall spacec, between bones yet the bcam e~p,llld~ to Lrradiate n l.arge port-Loll oi.- the heart. 'tn practice, the acou~tic wlndow 2~ in the tran.s(lllcer hollsin~ 16 mn~t be in physical con~acL with the heart 34 or the abc10n1e1l (not shown), respect-ively, in order that ultrasound may be tra1lsmitte(1. Either ~1ater, saline or an acoustic coupli1lg gel may he used to maintaln contact between the acoustic window 24 and the hody.
The -LrradLfltor for appllcatlo1ls Ln de~ibrillat-Lon Is shown gen-erally at 40 in ~figures 3 and 4. The Irradiatnr 40 consists of two main eleme1lts, an annular electrode 42 used to apply the electrical ener~y required for defibril]ation, and an ultrasound transducer 44 conslsting of several concentric rings of piezoelectric or other material, to pro~
duce ultrasoulld energy whLch may be directed into the body at an angLe dependent on tlle relatlve size of the concentric rLngs 44. The ultra-sound and electrical energy is inltiated hy a pushbutton 46 attached to the irradiator 40 whLch ls connected to the programrnable cdeflb-rillator circult, to be described below.
In practLce, tile ultrasound tra1lsducer defibrillator paddle 40 ls a,oplied to tlle chest in the region of an intercostal space overlylng the heart, physical contact ~ith the thorax ls rDade by the u~e of an acoustically and electrically conductive gel or a saline solution. The return defibrlllator electrode of conventional design ~not shown) is 2() placed as in conventiollaL practice. The type of fibrLllation to be treated ls seLected from the console and tl1e button on the handle pushed to activate the device. Further, the same instrurne1lt may be used for deflbrillat~on in an inoperative setttng with lower electrical energy appl:Led .
The ~system shown in figure 1 inclucles one of the ultrasound transducers described above, a radio fre~1ency electrical generator 50 which Is activated by a pulse ~odule 52 controlled to produce pulses allowing ultrasound from continuous wave to 3 ~ec pulses by a program-mable electrocardiogr;1ph (EKG) coinc-Ldence circuit 54, and a programmable deEibrlllator colncLdellce circuit 56.
A ~)ulse of ultrasonlc ener~y of varlable duration and intensLty related to critical events in the card-inc cycle may be prodl1cecl as shown in iigure 7. The ~K(; signal is acquired hy conventional EKG electrocdes 60 and 62 and ampli~lec1 by n hi~h ~ain a1npliEler 64 to prodl1ce the XKG
35 si,c~1lal 70, sho~Jn in flf~urf: 7. lhe 1~K(~ n;ll 7() i~s ~haped in a ~Lmin~

start r1Jlse 72 by a d1~crLmLna-or circuLt, showll genera:L1y at 74 ln flg.
5. T11e dLscrimir1atnr circ1lLt 74 ac.tLvates a ~el.ay circu:Lt 78, as .showll in fig. 5, whic11 1)rovides tl1e aE~I~rol)r1.ate de.l.ay interval. 80 (f:L~. 7) and may ~e adjnste(l alltomct:Lca1:Ly or extern;11.1.y to compensate ~or heart rate and cr1tical ev~llts witllin tlle heart ~ertain:l.rlg to the conditlon wl1ic}1 is being treated. Ttle del.ay intervA:L ge~1erat-Lng ci.rcui.t triggers an ul.tra-~sonlll1 ~atn~ pu.Lse circl.1it 82 whlcil produces ~ gflting waveform 84 of adJustabl.e widtll from 3 sec to Lnfinite length~ T}1e ~ating ~Javeform 84 is appLLed to radlo frequer1cy (r.f.) wave 86 in the pulse module circuit to generate a pul.sed radio frequency waveform 90. This pulsed r.f.
waveform 90 is amplified by the generator clrcult 92 and the amp].ified waveform 94 is applied to an ultrasonic transducer to produce ultrasonic energy at appropriate tisnes with respect to the cardiac cycle.
Furtl1er to the above circuits, a programmable defibrillator circuit (sho~l at 100 in figure 6) may he used for ultrasonic treatment tQ improve recovery irom de~ibrillation. Electrical de~ibrill.ation may he applied in the absence of EKG a~s occurs with ventricular fibrillation or synchronized ~o the EKG for inver.sion of atrial fibrillation by use of a mode switch 101. In eitl1er case, once tlle heart is beating, the ultra-sound may be applied at critical intervals withil1 the cardiac cycle asdescribed previously. The circuits descrlbed allow ultrasound to he applied ~or predetermined and accurate1.y controlled times with respect to the de~ibrillation pulse or accurately app~ied wLth respect to the con-traction of t)le heart and the elec~rical de~lbrillation pulse, in order to improve cardiac performance.
Tl1e operational se~luence 8hOWIl in figure 8 is init:iated by a short pulse 102 from the pushbutton switch 46 (figure 6) on the deflbril-lator 40. If EKG synchronizatiol1 has beer1 selected, tlle EKG signal 70, from patient electrodes 60 and 62, is formed into the discri.minated EKG
pulse 104. The rKG pulse 104 ln turn activates two delay circuits 108 and 110, the ultrasollnd timLng clrcult 114~ and tlle deflbrll].ator timing ci.rcuit 118 (shown in ~igure 6). The l.engLl1s oi tlle.se two del.ays 119 and 120 specify the order of occurrence of defibril1at:Lon ar1d ultrasound irradiat-Lon. Ir~ most ca.ses of vr.~ntrl.cl11.1r f:Lhri:Llation, appllcatLon of ultrasoulld :1s i.n-i.t~ated pr1Or to dei.ll-rl11atf.oll, where;1s l.n C.Ome ca.~es of - ~3 --atr-Lal fibrillatlon> the two evellts nee(l to be Losely syncllronized as descrihecl previously. The deFLhrLIlator clelay pulse 120 actuates a de-fLbrillator start clrcuit 118, whlcll sends a defLbrillator start pulse 121 to a deFLhrillator unit. Tlle ultrasound delay 108 actLvates an ultrasound gating circult, the output of which (125) is app]Led to the synchronized ultrasoulld gel-eratillg circn1ts (lescrLbed prevLollsly to produce ultrasoulld energy wllich Ls applled to the heart.

Claims (8)

CLAIMS:

1. An apparatus for ultrasonic enhancement of cardiac contractil-ity, comprising:
- means for detecting or programming a heart beat cycle, - means for generating ultrasound, - means for providing pulses of said ultrasound, and - means to time each said pulse to coincide with a selected event in the cardiac contraction cycle.

2. The apparatus of claim 1 wherein said means for detecting a heart beat cycle is an electrocardiograph.

3. The apparatus of claim 1 wherein said means for generating ultrasound is combined with one electrode of a pair of defibrillator electrodes.

4. The apparatus of claim 1 wherein a focussing element is pro-vided on said ultrasound generating means, for directing the ultrasound to pass between adjacent ribs in a patient's chest and then diverge to contact a greater area of the heart.

5. The apparatus of claim 1 wherein the ultrasound generating means is located in, or feeds into, a catheter probe.

6. The apparatus of claim 1 wherein a signal is acquired by EKG
electrodes and said means for providing timed pulses includes a discrim-inator circuit, a delay circuit, a ultrasound gating pulse circuit, and a radio frequency pulse module circuit for providing pulsed radio frequency to said means for generating ultrasound.

7. The apparatus of claim 1 wherein the ultrasound generator is adapted to generate ultrasound of frequency within the range of about 20 KHz to about 25 MHz.

8. An apparatus for heart defibrillation and ultrasonic enhance-ment of cardiac contractility comprising means for generating ultrasound combined with one electrode of a pair of electrical defibrillator electrodes.