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Prophylactic use of lanatoside C in auricular paroxysmal arrhythmias
PROPHYLACTIC
USE OF LANATOSIDE C IN AURICULAR PAROXYSMAL ARRHYTHWAS RALPH &1. TANDOWSKY, JI.13. Los ANGELES, CALIF. IKTRODUCTIOX
D
IGITALIS preparations, particularly the most recently isolated glycosides, have been used for some time in the abortive treatment of the paroxysmal auricular arrhythmias.’ Published accounts of this therapy pay little attention to the use of these digitalis bodies as a means of preventing frequent recurrences of these disturbing arrhythmias. This report is concerned, in the main, with this phase of therapy. Although the data presented are meager, the results obtained offer encouragement for further st,udy. The use of lanatoside C* orally in preference to other preparations of digitalis seems reasonable because this drug acts with rapidity, yet with minimal toxic effect, and retains its pharmacologic potency it1 vivo for at least twenty-four hours.“’ 3 The effect, of this drug has been demonstrated both electrocardiographically and clinically* to be without variability, whereas other preparations of digitalis act with marked Furthermore, the toxic effects of this drug, when adinconsistency.5 ministered over a prolonged period of time, are less than those of other digitalis preparations iti common use.6 MECHAKISM OF .\CTION Digitalis and its derivatives have a tendency to slow the rate of the heart in auricular paroxysmal arrhythmias, and often restore normal rhythm. The effect, is not unlike vagal stimulation. Slowing of the heart rate without abolition of heterogenetic auricular activity, as demonstrated by the electrocardiogram (Figs. 1 and 2), may be noted either before the termination of an attack or as a fleeting change during the course of t.he arrhythmia. Digitalis acts directly on the heart muscle and indirectly by stimulating the vagus nerves. In the presence of auricular fibrillation and flutter. the increase in “circus rate” attributed to the action of this drug is apparently due to increased vagal tone, which shortens t,he refractory period of auricular muscle. The slowing effect on the venlricle is apparently due to both direct and indirect depression of conductivity in the atrioventricular node. In the presence of paroxysmal auricu1a.r taehycardia and flutter, t.he From the Medical Wards of the Los .\nwlw General Hospital. Colleecr~of Medical Evangelists’ Division. Received for publication March 20. 1944. *Lanatoside C is marketed by Sandoz Chemical Works, Inc., under the name OP Cedilanld. 71
TANDOWSKY
:
PROPHYLACTIC
USE
OF
L:\N;\TOSIDE
C
73
Fig. 2.-Lanatoside C in auricular flutter; Case 6. A, Taken prior to administration of drug. Auricular rate, approximately 250 per mmuce. Ventricular rate, approximately 122 per minute. B, Taken forty minutes after the administration of 1.6 mg. lanxtoside C intravenoualr. Auricular rate. 62. Vwtricular rate, 67 per minute. Note marked sinus effect with w-wtahlishtnent of sinus rhythm. C, Taken six Not*.: months after initial paroxysm. Patient receiving (I.5 nag. I:snatosidc (‘ &Lily. minimal digitrllis pffwt on the S-T srgments.
effect of digitalis c~~nc~f \pet*y LI-c~I!l)e d11r t,o shortening of the refra,ctory period of’ auricnlar i~~usclr. Its effect must depend on its nodal action, or IIII sot11(’ ~~nkno~\-n a(ation on the 1~ellI’OIIIlIs(:Ular mechanism. It has been S~ICIIV~Ithal cligibalis ac+s npon auricular muscle by increasing its effectiv(i rfbfl*a(,tot.y pc,riud :IIK~ by depressing it,s conductivity.‘-” The abolition 01 ;I ~)ar’os)sut of tachycardin 01’ flutter cannot well be due to this a~iion, t’or the irrclirt& vagal action of the drug upon aut*icalar mus(~le an(l the eRcc:ts (,I‘ digitalizat.ion and vagal stimulation in these arrhythmias are similar. I,ittle is known regarding the action of digitalis on the rate: of itnpulsc: l’ormation in aurieular muscle. It seems logical to ass~wte, with thcb litnitetl knowledge at Our disposal. t,hat digitalis abolishes these arrhythmias by exerting some effect, on the nodal tissues. Clinical observatjion has proved the usefulness of rapidly acting digitalis g~lyc~osirles iti the thcr*ap;v of supraventricular arrhythmias, and, although their motlc of action is still somewhat obscure, further clinical investigation offers the ot11y method that will reveal the unThe ftw~uet~cyv of recdnrrence of t,hese known physiologic f:tet ors. arrhythmias is tlifific*nlt to explaill, l)ut their appearanrr demands an rfficitlnt thel.;\peutic investigatioti. It is hoped that this mode of therilf)y \2.ill rceei\rcJ lllore attetitioli, atl(l that th(, pt~oc:c~(lure herein briefly onf lined will offthr ;I basis for fnt*t her study.
Wit,h the exception 01 on(‘, thoscl under observation were known to have had recurrent attacks of ;Illl’icular paroxTsma1 tachycardia and This was confirmed elW r~oc;rrdioet’apl~lcally. The immediate flutter. attack rectlivetl first consitlerntiolr. and was trtlatta(l I)y giving lanatoside C1 in a dose of 1.6 mp. int.l,avcriollslv. After cthssation of the paroxYStll, the dYLlg WAS givc,n Ol’~lll~. iill. ~1 the close was determined by elecIt \riis felt that, when lninimal sagging of troca,rtliogl.al)hic c~riteria. the I#-T segtnctlt ill one or I~OIY leads was present, there was adequate prophyl;~.ctic saturation with the tlrug. This minimal eRect 011 the electrocal~djo~~~an~ has been c*c,llsistcntly rlrltlonstrated when lanatoII 11~s been noted that, when this drug side C has bee11 administerBed.” is given over a prolonged periotl elf time in amounis in excess of that which produces the minimal rlrc,t.rocarcliographic effect, premature velltricular co111ractiotls oft,en i)roclucecl disturbing symptoms. Each patient in this series was seen at Ir;lst once ~:ery t,wo weeks through( ‘il t~~f111historical data were gathered out the entire period of study. at each visit, particnla~~ly relati\e f o Imtoward symptoms, produced of the arrhythmia. either by the drug OI‘ hp the r(l(‘nrr’erlc( Those under observatiot~ JV(JIY alI ambr~l;ltc~t~y. RIIC] WPI’C allowed to carry 011 In some. achcessory medication their normal envircmmrntnl routines. was administorecl whtstl tlrcessa J*J-. iitlfl consisted. in t,he main, of mild sedatives such as the barbitnrattc~s or I)rc)mitlrs. Of the eight patients paroxpsms of anricular
observed in t,his study, six had ON or IXON flutter. ;ln(l two had frequent, at,tacks of par-
Auricular paroxysmal tachycardia
flutter
flutter
flnttw
flutter
Auricular
Auricular
4urirular
4uriculnr
4
5
6
*V.P.('.zVentricular
Auricular flutter 6 Auricular paroxysuml tachycardia 2
DIAGNOSIS
Auricular paroxys ma1 tachyrardla
3
flutter
Auricular
2
flutter
grcmature
IA.+%;
52 M
32 F
49 F
72 M
32 F
62 M
53 M
51 M
AGE (YE.1 SEX
PROPHYLACTIC
Auricular
DIAGNOSIS
I.
1
NUMBER
TABLE
0
Coronary arteriosclerosis 3 Old infarction 1 Rheumatic 1
iNz"""
mitral and aortic endo. carditis t :oronary arteriosclerosis
I ~hcumat.ic
1
'zz
4
32
30
n
5
24
14
14
arte-
8
PERIOD )FOBSER VATION (MO.1
C IX
artrriosclerosis
(:oronary
0
anterior infarction
(31d
riosclerosis
contractions.
-.
ASSOCIATED CARDIAC DISEASE
OF LANATOSIDE
,Coronary
USE
ZZ
lam C
Totals
1.6 mg. lanatoside C
..6 mg. atoside
1.6 mg. lanat.oside C
xtoside C
1.6 mg. lan-
6.5 mg. lanat,oside C
I.6 mg. lanatoside C
..6 mg. Ianatoside C
1.6 mg. lanatoside C
PAROXYShIS
DRUGTREAT MENTOF
AVRICULAR
-
-
-
--
=
4.2
AVERAGE
0
3
4
A
8
3
4
6
-
--
-
MONTHS PRIOR T O MEDICATION
12
NUMBER CIF PAROX YSMS IN
PAROXYSMAL
-
_-
=Z
0.37
AVERAGE
0
0
0
0
1 Following Iaparotomp
1 Alcoholic debauch 1 Discontin1 ied,“,F;g
0
PAROXYSMS WHILE UNDER OBSERVATION
NUMBEROF
ARRHYTHMIAS
ON
1 Thiamin
0
1
2,000 R.U. estrogenic substance weekly Bromides 30 grains daily 2,000 R.U. estrogenic substance weekly Phenobarbital 1 grain daily
1% grains phenobarI bital daily
Phenobarbital 1 grain daily Thiamin 30 mg. daily
MEDICATION
ACCESSORY
DATA
ECG EFFECT
CASES
PROPIIYLACTIC DOSAGE
1.I)
0.5
0.5
0.5
0.5
0.5
0.5
DOSAGE MQ. DAILY
case
-I0.51 mg.mg.dailydaily 1 7
0
V.P.(‘.
n
0
0
V.P.C.
0
v.p.c.*
EFFECTS
WARD
UNTO-
OBSERVED
76
\.\I liliIf’.\S
It is ititereslitlg gtWUp
avelxp3I
that, l)rior 4.2
1111: \HT
.lOITRS,tI,
to tlita t:tnatc~sitle (’ tttrtlic7~tiott,
pal’osysttls
itt
ii t welve-ntonth
Iwriotl.
thf~
rutir*fL
.\l;lirltetl;iilw
therapy \vith Itt~~;ttc)sitlf: (’ o\‘t’r :III i~~et~~tgt~prt*io(l of fit’t~tt ntt)llths reduced the inc*idettc*tJ ot’ lwurt’efif~f~ to O.:i’i. l’titt r~iaittlf~tiat~vf~ tlow in all hut One CiMf’ clicl Irot eXtWd 0..5 lng. tlailj-. ‘t’hrct~ oi’ itt(b I);iticlnts hat1 one rt~~ll~rt~tt(*e 01’ tiltdhytxar(lia clm’ittg thr peCo(l 01’ c)l)set,v;ltion. In Ollf! CaSP it IJ~ltYJX~Slll l’OllO\~e~t 1111 alcc~liolic~ ~lt’lJiltlf’ll. iti iltlOthf’t’ it followed discontitlttattve 01’ the ~IYI: for ;I periotl 01’ ottv \\.ctBk. :III(I itt the third the at’rhythntia 11lat1r its ill)l)ral.altt*r itrtrrtc+liatrly itt’tet* Ial)Fll@OtOllly
for
gill1
tJlZltltl~1~
cliwaw.
‘I’hP
I’t’~lll’l’f’tl~‘t’S
itl
iltt
tllYf’P
\Vf’l’f’
exlrentely shot*t tlllral ion, illlfl (~;I(~11 ;th:~tc’tl witltotii sl)ecaial l~lc~~licilti0~1. The electl,ocartljo~t.;tl)hi(~ efiec*l of l;tll;tt(jsicle ( * \V;IS cJlJSf?l’\f’ll itl :I]] Of l-he CiMeS, atIt this f~EW1 iIt II0 titti(L CllJiltf?tl ulttit 1 IIt, tltYlg \\‘aS discontinued for il petGiocl of tllrec~ tl;lys ot’ ltl01’f’. This f&cd cv)mistecl of a slight sagging of the RS-T segment, will1 or without flattcnittg ot’ the T ~lrave. III three itistaticrs, l~(~zuse of gf~tlf~txl ilppt~eht~llSi0tl. it I$$ grains ot’ phellolt;trhit;tI it1 di\,itletl (lost’s, \I.ilS necessary to give One patient rcc*rivetl 30 gl’iliIlS Ol’ tripIf> tJtT~llliClCS tlilit.Y, iltlll t\VO womeliJ hecause of c*lim:rc+eric~ symptoms, receirc~c I ~~eckly i njt~ciions ()tie patietii, hecause of itttl~r~ltdiii~ ~~t~i~il~lit~ral of estrogeuic subst:tttce. neuritis, received 30 tttp. of thialtiiit CliLily. TllfJ Ollly ~]lltOIVitl’(L fltitlct tltitt CY)Ul(l ~HJSSihl?; l)(l attril~utetl 10 tilt’ use of this drug l~roph~~lacti~~~ll~-\f.its tlte ocf~~~t~t~f~ttf~ ot’ ~entric~rtl:rr premature contra&ions in three f+asw.
of
It appears that lanatoside (’ in SOllIe unknown way reduced the recurrence frequency of paroxysmal auricular tachgcardia and flutter in eight casesfrom 4.2 in n tu-elre-month period to 0.3’7in a fifteen-month period, following the use of ihe same drug in full cligitalizing dosage The amount of tlrug usetl prophyat the onset of an initial p;~r~r~systt~. lactically did ltot exceed 0.5 111~. claily in seren vases; in the eighth the dosage was 1 mg. Electrocardiographic evidence of the effect of the drug on the RS-T segment and T wave was noted. Associated
TANDOWSKY
:
PROPHYLACTIC
USE
OF
L.1SATOSIDE
C
77
cardiac lesions in no way altered the result. The only untoward effect was the appearance, from time to time, of ventricular premature conIn three instances one paroxysm occurred recurrently, and tractions. in each of these a definite causative factor was t~stablished. The results obtained constitute evidence of the value of this (Irug for prophylactic therapy in basks of pa~o~~~mal aul*icl\lal~ t;l(*hycardiil ancl fluttpr.
1. Lanatoside C appears to be of valut~ prophylactically in the treatment of paroxysmal auricular tachycardia and flutter, provided thtt therapy is commenced by giving it intravenously to stop a paroxysnl. 2. The effective prophylactic dose varied from 0.5 to I mg. daily. 3. Characteristic electrocardiographic changes may be used as a criterion of the effect of the drug. 4. Lanatoside (>, because of properties discussec! in this article, may be considered preferable to other digitalis preparations for prophylactic therapy. REFERENCES A Preliminary Investigation of the Therapeutic Value G., and La Due, J.: of Lanatoside C, AM. HEART J. 21: 133, 1941. 2. Chamberlain, F. L., and Sokolow, M.: Clinical Experience With the Oral Administration of Cedilanid and a Comparison of the Oral and Intravenous Preparations of Cedilanid With Digitalis Purpurea, AM. HEART J. 23: 245, 1942. 3. Kosenblum, H., Biskind, G., and Iirieger, H. E.: The Efietats of Repeated Administration of Lanatoside (1 on the MIpoc7irdium of the Dog, .1hc. HEART .T. 1. Fahr,
24:
73-I,
1942.
An Electroc*ar~liogr:tphic 4. Tandowsky, R. &I.: and Clinical Stutly of Lanatoside C, AM. HEART J. 24: 472, 19X 5. Tandowsky, R,. M., Anderson, Norma, and Vandeventer, J. E;.: An Electrocardil,graphic and Clinical Study of Various So-Called (!ardi:tca l)rugs, ,411. HEAK~I‘ J. 28: 29S, 1944. 6. Visscher, M. B., and Peters, H. C.: The Energy hletabolism of the Heart iu Failure and t,he Influence of Drugs rpon It, Akzr. HEART J. 11: 273, 1936. 7. Lewis, T., Drury, A. N., and Iliescu, C. C.: Some Observations Upon Atropine and Strophanthin, Heart 9: 21, 1921. Lewis, T., and Drury, A. N.: Revised Views of the Refractor>Period in Relation to the Drugs Reputed to Prolong It, and in Relation to Circus Nov+ ment, Heart 13: 1926. The hlrcllanisn~ of .~nyi(zul:lr 8. Barker, P. S., Wilson, F. N., and Johnston, F. D.: Paroxysmal Tachycardia, AX. HEART J. 26: 435, 19-l-R. 9. Author’s observations during the 1as.t three pears.
USE OF LANATOSIDE C IN AURICULAR PAROXYSMAL ARRHYTHWAS RALPH &1. TANDOWSKY, JI.13. Los ANGELES, CALIF. IKTRODUCTIOX
D
IGITALIS preparations, particularly the most recently isolated glycosides, have been used for some time in the abortive treatment of the paroxysmal auricular arrhythmias.’ Published accounts of this therapy pay little attention to the use of these digitalis bodies as a means of preventing frequent recurrences of these disturbing arrhythmias. This report is concerned, in the main, with this phase of therapy. Although the data presented are meager, the results obtained offer encouragement for further st,udy. The use of lanatoside C* orally in preference to other preparations of digitalis seems reasonable because this drug acts with rapidity, yet with minimal toxic effect, and retains its pharmacologic potency it1 vivo for at least twenty-four hours.“’ 3 The effect, of this drug has been demonstrated both electrocardiographically and clinically* to be without variability, whereas other preparations of digitalis act with marked Furthermore, the toxic effects of this drug, when adinconsistency.5 ministered over a prolonged period of time, are less than those of other digitalis preparations iti common use.6 MECHAKISM OF .\CTION Digitalis and its derivatives have a tendency to slow the rate of the heart in auricular paroxysmal arrhythmias, and often restore normal rhythm. The effect, is not unlike vagal stimulation. Slowing of the heart rate without abolition of heterogenetic auricular activity, as demonstrated by the electrocardiogram (Figs. 1 and 2), may be noted either before the termination of an attack or as a fleeting change during the course of t.he arrhythmia. Digitalis acts directly on the heart muscle and indirectly by stimulating the vagus nerves. In the presence of auricular fibrillation and flutter. the increase in “circus rate” attributed to the action of this drug is apparently due to increased vagal tone, which shortens t,he refractory period of auricular muscle. The slowing effect on the venlricle is apparently due to both direct and indirect depression of conductivity in the atrioventricular node. In the presence of paroxysmal auricu1a.r taehycardia and flutter, t.he From the Medical Wards of the Los .\nwlw General Hospital. Colleecr~of Medical Evangelists’ Division. Received for publication March 20. 1944. *Lanatoside C is marketed by Sandoz Chemical Works, Inc., under the name OP Cedilanld. 71
TANDOWSKY
:
PROPHYLACTIC
USE
OF
L:\N;\TOSIDE
C
73
Fig. 2.-Lanatoside C in auricular flutter; Case 6. A, Taken prior to administration of drug. Auricular rate, approximately 250 per mmuce. Ventricular rate, approximately 122 per minute. B, Taken forty minutes after the administration of 1.6 mg. lanxtoside C intravenoualr. Auricular rate. 62. Vwtricular rate, 67 per minute. Note marked sinus effect with w-wtahlishtnent of sinus rhythm. C, Taken six Not*.: months after initial paroxysm. Patient receiving (I.5 nag. I:snatosidc (‘ &Lily. minimal digitrllis pffwt on the S-T srgments.
effect of digitalis c~~nc~f \pet*y LI-c~I!l)e d11r t,o shortening of the refra,ctory period of’ auricnlar i~~usclr. Its effect must depend on its nodal action, or IIII sot11(’ ~~nkno~\-n a(ation on the 1~ellI’OIIIlIs(:Ular mechanism. It has been S~ICIIV~Ithal cligibalis ac+s npon auricular muscle by increasing its effectiv(i rfbfl*a(,tot.y pc,riud :IIK~ by depressing it,s conductivity.‘-” The abolition 01 ;I ~)ar’os)sut of tachycardin 01’ flutter cannot well be due to this a~iion, t’or the irrclirt& vagal action of the drug upon aut*icalar mus(~le an(l the eRcc:ts (,I‘ digitalizat.ion and vagal stimulation in these arrhythmias are similar. I,ittle is known regarding the action of digitalis on the rate: of itnpulsc: l’ormation in aurieular muscle. It seems logical to ass~wte, with thcb litnitetl knowledge at Our disposal. t,hat digitalis abolishes these arrhythmias by exerting some effect, on the nodal tissues. Clinical observatjion has proved the usefulness of rapidly acting digitalis g~lyc~osirles iti the thcr*ap;v of supraventricular arrhythmias, and, although their motlc of action is still somewhat obscure, further clinical investigation offers the ot11y method that will reveal the unThe ftw~uet~cyv of recdnrrence of t,hese known physiologic f:tet ors. arrhythmias is tlifific*nlt to explaill, l)ut their appearanrr demands an rfficitlnt thel.;\peutic investigatioti. It is hoped that this mode of therilf)y \2.ill rceei\rcJ lllore attetitioli, atl(l that th(, pt~oc:c~(lure herein briefly onf lined will offthr ;I basis for fnt*t her study.
Wit,h the exception 01 on(‘, thoscl under observation were known to have had recurrent attacks of ;Illl’icular paroxTsma1 tachycardia and This was confirmed elW r~oc;rrdioet’apl~lcally. The immediate flutter. attack rectlivetl first consitlerntiolr. and was trtlatta(l I)y giving lanatoside C1 in a dose of 1.6 mp. int.l,avcriollslv. After cthssation of the paroxYStll, the dYLlg WAS givc,n Ol’~lll~. iill. ~1 the close was determined by elecIt \riis felt that, when lninimal sagging of troca,rtliogl.al)hic c~riteria. the I#-T segtnctlt ill one or I~OIY leads was present, there was adequate prophyl;~.ctic saturation with the tlrug. This minimal eRect 011 the electrocal~djo~~~an~ has been c*c,llsistcntly rlrltlonstrated when lanatoII 11~s been noted that, when this drug side C has bee11 administerBed.” is given over a prolonged periotl elf time in amounis in excess of that which produces the minimal rlrc,t.rocarcliographic effect, premature velltricular co111ractiotls oft,en i)roclucecl disturbing symptoms. Each patient in this series was seen at Ir;lst once ~:ery t,wo weeks through( ‘il t~~f111historical data were gathered out the entire period of study. at each visit, particnla~~ly relati\e f o Imtoward symptoms, produced of the arrhythmia. either by the drug OI‘ hp the r(l(‘nrr’erlc( Those under observatiot~ JV(JIY alI ambr~l;ltc~t~y. RIIC] WPI’C allowed to carry 011 In some. achcessory medication their normal envircmmrntnl routines. was administorecl whtstl tlrcessa J*J-. iitlfl consisted. in t,he main, of mild sedatives such as the barbitnrattc~s or I)rc)mitlrs. Of the eight patients paroxpsms of anricular
observed in t,his study, six had ON or IXON flutter. ;ln(l two had frequent, at,tacks of par-
Auricular paroxysmal tachycardia
flutter
flutter
flnttw
flutter
Auricular
Auricular
4urirular
4uriculnr
4
5
6
*V.P.('.zVentricular
Auricular flutter 6 Auricular paroxysuml tachycardia 2
DIAGNOSIS
Auricular paroxys ma1 tachyrardla
3
flutter
Auricular
2
flutter
grcmature
IA.+%;
52 M
32 F
49 F
72 M
32 F
62 M
53 M
51 M
AGE (YE.1 SEX
PROPHYLACTIC
Auricular
DIAGNOSIS
I.
1
NUMBER
TABLE
0
Coronary arteriosclerosis 3 Old infarction 1 Rheumatic 1
iNz"""
mitral and aortic endo. carditis t :oronary arteriosclerosis
I ~hcumat.ic
1
'zz
4
32
30
n
5
24
14
14
arte-
8
PERIOD )FOBSER VATION (MO.1
C IX
artrriosclerosis
(:oronary
0
anterior infarction
(31d
riosclerosis
contractions.
-.
ASSOCIATED CARDIAC DISEASE
OF LANATOSIDE
,Coronary
USE
ZZ
lam C
Totals
1.6 mg. lanatoside C
..6 mg. atoside
1.6 mg. lanat.oside C
xtoside C
1.6 mg. lan-
6.5 mg. lanat,oside C
I.6 mg. lanatoside C
..6 mg. Ianatoside C
1.6 mg. lanatoside C
PAROXYShIS
DRUGTREAT MENTOF
AVRICULAR
-
-
-
--
=
4.2
AVERAGE
0
3
4
A
8
3
4
6
-
--
-
MONTHS PRIOR T O MEDICATION
12
NUMBER CIF PAROX YSMS IN
PAROXYSMAL
-
_-
=Z
0.37
AVERAGE
0
0
0
0
1 Following Iaparotomp
1 Alcoholic debauch 1 Discontin1 ied,“,F;g
0
PAROXYSMS WHILE UNDER OBSERVATION
NUMBEROF
ARRHYTHMIAS
ON
1 Thiamin
0
1
2,000 R.U. estrogenic substance weekly Bromides 30 grains daily 2,000 R.U. estrogenic substance weekly Phenobarbital 1 grain daily
1% grains phenobarI bital daily
Phenobarbital 1 grain daily Thiamin 30 mg. daily
MEDICATION
ACCESSORY
DATA
ECG EFFECT
CASES
PROPIIYLACTIC DOSAGE
1.I)
0.5
0.5
0.5
0.5
0.5
0.5
DOSAGE MQ. DAILY
case
-I0.51 mg.mg.dailydaily 1 7
0
V.P.(‘.
n
0
0
V.P.C.
0
v.p.c.*
EFFECTS
WARD
UNTO-
OBSERVED
76
\.\I liliIf’.\S
It is ititereslitlg gtWUp
avelxp3I
that, l)rior 4.2
1111: \HT
.lOITRS,tI,
to tlita t:tnatc~sitle (’ tttrtlic7~tiott,
pal’osysttls
itt
ii t welve-ntonth
Iwriotl.
thf~
rutir*fL
.\l;lirltetl;iilw
therapy \vith Itt~~;ttc)sitlf: (’ o\‘t’r :III i~~et~~tgt~prt*io(l of fit’t~tt ntt)llths reduced the inc*idettc*tJ ot’ lwurt’efif~f~ to O.:i’i. l’titt r~iaittlf~tiat~vf~ tlow in all hut One CiMf’ clicl Irot eXtWd 0..5 lng. tlailj-. ‘t’hrct~ oi’ itt(b I);iticlnts hat1 one rt~~ll~rt~tt(*e 01’ tiltdhytxar(lia clm’ittg thr peCo(l 01’ c)l)set,v;ltion. In Ollf! CaSP it IJ~ltYJX~Slll l’OllO\~e~t 1111 alcc~liolic~ ~lt’lJiltlf’ll. iti iltlOthf’t’ it followed discontitlttattve 01’ the ~IYI: for ;I periotl 01’ ottv \\.ctBk. :III(I itt the third the at’rhythntia 11lat1r its ill)l)ral.altt*r itrtrrtc+liatrly itt’tet* Ial)Fll@OtOllly
for
gill1
tJlZltltl~1~
cliwaw.
‘I’hP
I’t’~lll’l’f’tl~‘t’S
itl
iltt
tllYf’P
\Vf’l’f’
exlrentely shot*t tlllral ion, illlfl (~;I(~11 ;th:~tc’tl witltotii sl)ecaial l~lc~~licilti0~1. The electl,ocartljo~t.;tl)hi(~ efiec*l of l;tll;tt(jsicle ( * \V;IS cJlJSf?l’\f’ll itl :I]] Of l-he CiMeS, atIt this f~EW1 iIt II0 titti(L CllJiltf?tl ulttit 1 IIt, tltYlg \\‘aS discontinued for il petGiocl of tllrec~ tl;lys ot’ ltl01’f’. This f&cd cv)mistecl of a slight sagging of the RS-T segment, will1 or without flattcnittg ot’ the T ~lrave. III three itistaticrs, l~(~zuse of gf~tlf~txl ilppt~eht~llSi0tl. it I$$ grains ot’ phellolt;trhit;tI it1 di\,itletl (lost’s, \I.ilS necessary to give One patient rcc*rivetl 30 gl’iliIlS Ol’ tripIf> tJtT~llliClCS tlilit.Y, iltlll t\VO womeliJ hecause of c*lim:rc+eric~ symptoms, receirc~c I ~~eckly i njt~ciions ()tie patietii, hecause of itttl~r~ltdiii~ ~~t~i~il~lit~ral of estrogeuic subst:tttce. neuritis, received 30 tttp. of thialtiiit CliLily. TllfJ Ollly ~]lltOIVitl’(L fltitlct tltitt CY)Ul(l ~HJSSihl?; l)(l attril~utetl 10 tilt’ use of this drug l~roph~~lacti~~~ll~-\f.its tlte ocf~~~t~t~f~ttf~ ot’ ~entric~rtl:rr premature contra&ions in three f+asw.
of
It appears that lanatoside (’ in SOllIe unknown way reduced the recurrence frequency of paroxysmal auricular tachgcardia and flutter in eight casesfrom 4.2 in n tu-elre-month period to 0.3’7in a fifteen-month period, following the use of ihe same drug in full cligitalizing dosage The amount of tlrug usetl prophyat the onset of an initial p;~r~r~systt~. lactically did ltot exceed 0.5 111~. claily in seren vases; in the eighth the dosage was 1 mg. Electrocardiographic evidence of the effect of the drug on the RS-T segment and T wave was noted. Associated
TANDOWSKY
:
PROPHYLACTIC
USE
OF
L.1SATOSIDE
C
77
cardiac lesions in no way altered the result. The only untoward effect was the appearance, from time to time, of ventricular premature conIn three instances one paroxysm occurred recurrently, and tractions. in each of these a definite causative factor was t~stablished. The results obtained constitute evidence of the value of this (Irug for prophylactic therapy in basks of pa~o~~~mal aul*icl\lal~ t;l(*hycardiil ancl fluttpr.
1. Lanatoside C appears to be of valut~ prophylactically in the treatment of paroxysmal auricular tachycardia and flutter, provided thtt therapy is commenced by giving it intravenously to stop a paroxysnl. 2. The effective prophylactic dose varied from 0.5 to I mg. daily. 3. Characteristic electrocardiographic changes may be used as a criterion of the effect of the drug. 4. Lanatoside (>, because of properties discussec! in this article, may be considered preferable to other digitalis preparations for prophylactic therapy. REFERENCES A Preliminary Investigation of the Therapeutic Value G., and La Due, J.: of Lanatoside C, AM. HEART J. 21: 133, 1941. 2. Chamberlain, F. L., and Sokolow, M.: Clinical Experience With the Oral Administration of Cedilanid and a Comparison of the Oral and Intravenous Preparations of Cedilanid With Digitalis Purpurea, AM. HEART J. 23: 245, 1942. 3. Kosenblum, H., Biskind, G., and Iirieger, H. E.: The Efietats of Repeated Administration of Lanatoside (1 on the MIpoc7irdium of the Dog, .1hc. HEART .T. 1. Fahr,
24:
73-I,
1942.
An Electroc*ar~liogr:tphic 4. Tandowsky, R. &I.: and Clinical Stutly of Lanatoside C, AM. HEART J. 24: 472, 19X 5. Tandowsky, R,. M., Anderson, Norma, and Vandeventer, J. E;.: An Electrocardil,graphic and Clinical Study of Various So-Called (!ardi:tca l)rugs, ,411. HEAK~I‘ J. 28: 29S, 1944. 6. Visscher, M. B., and Peters, H. C.: The Energy hletabolism of the Heart iu Failure and t,he Influence of Drugs rpon It, Akzr. HEART J. 11: 273, 1936. 7. Lewis, T., Drury, A. N., and Iliescu, C. C.: Some Observations Upon Atropine and Strophanthin, Heart 9: 21, 1921. Lewis, T., and Drury, A. N.: Revised Views of the Refractor>Period in Relation to the Drugs Reputed to Prolong It, and in Relation to Circus Nov+ ment, Heart 13: 1926. The hlrcllanisn~ of .~nyi(zul:lr 8. Barker, P. S., Wilson, F. N., and Johnston, F. D.: Paroxysmal Tachycardia, AX. HEART J. 26: 435, 19-l-R. 9. Author’s observations during the 1as.t three pears.