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The effects of antimony on the heart
4S2 "I'II\N~,.'~C'I'IO",S ()1,' 'I'HI~ ])tC)YAI. ~Ot:li
V~fl, :N.~. N(). (~. 2
'~'HF F.I:I"t~;C'F.<, ()I: A N T I M O N Y
ON THE HEART
I;Y
\V. O'BRIEN R(~yal :~rmy Medical College, ~'Iillbank
In \'Vest Africa during the second World War over 5,000 soldiers were treated for schistosomiasis. Amongst those receiving 40 - 60 ml. of stibophen the relapse rate was 86 per cent. compared with a relapse rate of 10 per cent. amongst those receiving tartar emetic. Similar poor results were obtained during the war with anthiomaline, the relapse rate after one course being between 70 and 80 per cent. Unfortunately tartar emetic was found to cause acute fatal liver necrosis in a small proportion of these men. Recent experience in treating West African soldiers has confirmed these poor results. Schistosoma haematobium infection in West Africa tends to become inactive by the time that the patients have reached the age of 40 years, and so this lack of effective treatment did not appear to be a matter for serious concern. More recently however, it has been shown by I'2DINGTON(1957) that the late effects of prolonged infection are a serious cause of death amongst West Africans, more serious in fact than malignant tertian malaria, and were due to chronic irreversible renal, ureteric and vesical changes. Vesical schistosomiasis is extremely c o m m o n amongst West African soldiers and in an attempt to deal with this problem an intensive course of
Fic. 1.
Standard lead 2 from patient having multiple Stokes-Adams attacks.
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.
7 .
.
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...............
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. . . . . . . . .
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Fie.
2.
Precordial
c h e s t ]cads V 1-7 i~n 6 c o n s e c l . l l i \ e
c a s e s ',ruder t r e a t m e n t
~
w i t h sti!,~pl~c~
V
FIG. 3.
7
V
I
3
5
7
Precordial chest leads V 1, 3, 5, 7, in 14 consecutive cases under treatment with stibophen
,,,.. {.,'IW, I I{N
~-Y~5
stibophen was given. These patients xvcrc all fit, well-nourished young men of ~,:~,od physique, and in view of Edington's work it seemed justifiable to proceed with this type ~:i" cou,sc. Over a period of 20 days 95 ml. of stibophcn were given. After initial graded d;~:..:.~, 5 ml. (4.2.5 rag. of trivalent antimony) of stibophen wcrc given daily bv the {~tra:~' ~ ( ~ rotltc.
One man during the course of treatme'.;t developed nndtiple Stokcs-Aciams attack:~ wi;ici~ the electrocardiograph (Fig. l) showed w~re due to gross vcntricular dysrhythmia. Tlic patic,~t recovered completely after the a&ninistra{ion of B.A.I, Following this experience an electrocardiograph was recorded towards the end of the course in all cases. "l'wcnty successive graphs were all abnormal (t:igs. 2 and 3). This abnormality was rcmarka~lv constant and consisted of an elevation of the ST segment followed by a sharp inversion ~f the T wave in the right ventricular nnipolar precordial leads. The T wave inversion ~)r depression sometimes extended over into the left ventricular leads. These chat~ges arc those of underlying heart muscle damage apparently of a temporary nature, for the graphs when repeated 3 months later had all returned to normal. Besides the usual toxic effects of antimony such as anorexia, nausea, vomiting, substcrnal constriction and dyspnoea, one patient developed severe sulphaemoglobinaernia, l:nfortunately the results of this intensive course after 3 months did not appear any better than the poor results previously obtained after the usual standard course of stibophen. I) ISCUSSION
MAINZER and KRAUSE (1940) had noticed sudden unexpected death of patients receiving standard doses of antimony, and they recorded electrocardiograms showing the standard multipolar leads of four patients receiving antimony. These revealed depression of the T wave in three and inversion in one, and they considered that the action of antimony on the heart muscle was the likely cause of such fatalities. AZAR and PIPKIN (1951) recorded the full electrocardiogram in a single case, which showed inversion of the T wave in the precordial leads V5 and V6. There appear to have been no other published electrocardiograms showing these changes in the British literature, though fuller graphs have been published from America and China. The remarkably constant changes seen in these cardiograms taken from West African soldiers may in part be due to the well-known ease with which ST elevation and inversion of the T wave may be induced in Africans, in response to many causes, and it is likely that stibophen would not cause such consistent changes in other races. The gross ventricular dysrhythmia illustrated in Fig. 1 suggests the probable mode of sudden death after intravenous antimony. HUANG MING, HSlN et al. (1958) have shown that gross ventricular dysrhythmias associated with Stokes-Adams attacks are common in Chinese patients receiving standard doses of tartar emetic, and sudden death during tartar emetic treatment in standard doses is known to occur in 0.2 per cent. of those receiving this treatment. The treatment of S. haematobium infection in West Africa remains unsatisfactory and, in particular, intensive courses are associated with constant and gross electrocardiographic changes in \Vest Africans. SUMMARY
Stibophen in large doses was given to West African soldiers as standard courses of treatment had been found ineffective. Constant electrocardiographic abnormalities were
486
T I l E FI:FI'X!TS (?,!: A N T I . \ t O N Y
ON TIlE
ttEART
recorded and one patient developed a severe ventricular dysrhythmia. treatment docs not appear advisable in W e s t Africans.
S u c h intensive
I),EI;I.'RENCES AZAR, J. E., TABJ~ARA,R. & PIp~4_IN,A. (1951). ~l)aizs. R. ,%c. tro#. 3led. tly~% 45, 383. EDINCTON, (;. M. (1957). W. :lfr. reed. ft., 2, 45. it.au~;(; :MIy~;, ItsIN et al. (1958). Cki~t. mad. J., 76, I(!3. Malxz~:n, F. & Knaus~, M. (1940). 7)'a~ts. R. So~. trop. ~,~led. 1tr,~., 33, 405.
V~fl, :N.~. N(). (~. 2
'~'HF F.I:I"t~;C'F.<, ()I: A N T I M O N Y
ON THE HEART
I;Y
\V. O'BRIEN R(~yal :~rmy Medical College, ~'Iillbank
In \'Vest Africa during the second World War over 5,000 soldiers were treated for schistosomiasis. Amongst those receiving 40 - 60 ml. of stibophen the relapse rate was 86 per cent. compared with a relapse rate of 10 per cent. amongst those receiving tartar emetic. Similar poor results were obtained during the war with anthiomaline, the relapse rate after one course being between 70 and 80 per cent. Unfortunately tartar emetic was found to cause acute fatal liver necrosis in a small proportion of these men. Recent experience in treating West African soldiers has confirmed these poor results. Schistosoma haematobium infection in West Africa tends to become inactive by the time that the patients have reached the age of 40 years, and so this lack of effective treatment did not appear to be a matter for serious concern. More recently however, it has been shown by I'2DINGTON(1957) that the late effects of prolonged infection are a serious cause of death amongst West Africans, more serious in fact than malignant tertian malaria, and were due to chronic irreversible renal, ureteric and vesical changes. Vesical schistosomiasis is extremely c o m m o n amongst West African soldiers and in an attempt to deal with this problem an intensive course of
Fic. 1.
Standard lead 2 from patient having multiple Stokes-Adams attacks.
'~'. ~,'1~:I~c>,
-1 -
} •
i,-~
4 - ~
'
5
,
~
~
6 :
.
.
7 .
.
b
2;~A2-.,L,
I
45;3
...............
i:
"---7
:
:
"
-
;
. . . . . . . . .
"; ........
7"
7
~r/=~-~]~
Fie.
2.
Precordial
c h e s t ]cads V 1-7 i~n 6 c o n s e c l . l l i \ e
c a s e s ',ruder t r e a t m e n t
~
w i t h sti!,~pl~c~
V
FIG. 3.
7
V
I
3
5
7
Precordial chest leads V 1, 3, 5, 7, in 14 consecutive cases under treatment with stibophen
,,,.. {.,'IW, I I{N
~-Y~5
stibophen was given. These patients xvcrc all fit, well-nourished young men of ~,:~,od physique, and in view of Edington's work it seemed justifiable to proceed with this type ~:i" cou,sc. Over a period of 20 days 95 ml. of stibophcn were given. After initial graded d;~:..:.~, 5 ml. (4.2.5 rag. of trivalent antimony) of stibophen wcrc given daily bv the {~tra:~' ~ ( ~ rotltc.
One man during the course of treatme'.;t developed nndtiple Stokcs-Aciams attack:~ wi;ici~ the electrocardiograph (Fig. l) showed w~re due to gross vcntricular dysrhythmia. Tlic patic,~t recovered completely after the a&ninistra{ion of B.A.I, Following this experience an electrocardiograph was recorded towards the end of the course in all cases. "l'wcnty successive graphs were all abnormal (t:igs. 2 and 3). This abnormality was rcmarka~lv constant and consisted of an elevation of the ST segment followed by a sharp inversion ~f the T wave in the right ventricular nnipolar precordial leads. The T wave inversion ~)r depression sometimes extended over into the left ventricular leads. These chat~ges arc those of underlying heart muscle damage apparently of a temporary nature, for the graphs when repeated 3 months later had all returned to normal. Besides the usual toxic effects of antimony such as anorexia, nausea, vomiting, substcrnal constriction and dyspnoea, one patient developed severe sulphaemoglobinaernia, l:nfortunately the results of this intensive course after 3 months did not appear any better than the poor results previously obtained after the usual standard course of stibophen. I) ISCUSSION
MAINZER and KRAUSE (1940) had noticed sudden unexpected death of patients receiving standard doses of antimony, and they recorded electrocardiograms showing the standard multipolar leads of four patients receiving antimony. These revealed depression of the T wave in three and inversion in one, and they considered that the action of antimony on the heart muscle was the likely cause of such fatalities. AZAR and PIPKIN (1951) recorded the full electrocardiogram in a single case, which showed inversion of the T wave in the precordial leads V5 and V6. There appear to have been no other published electrocardiograms showing these changes in the British literature, though fuller graphs have been published from America and China. The remarkably constant changes seen in these cardiograms taken from West African soldiers may in part be due to the well-known ease with which ST elevation and inversion of the T wave may be induced in Africans, in response to many causes, and it is likely that stibophen would not cause such consistent changes in other races. The gross ventricular dysrhythmia illustrated in Fig. 1 suggests the probable mode of sudden death after intravenous antimony. HUANG MING, HSlN et al. (1958) have shown that gross ventricular dysrhythmias associated with Stokes-Adams attacks are common in Chinese patients receiving standard doses of tartar emetic, and sudden death during tartar emetic treatment in standard doses is known to occur in 0.2 per cent. of those receiving this treatment. The treatment of S. haematobium infection in West Africa remains unsatisfactory and, in particular, intensive courses are associated with constant and gross electrocardiographic changes in \Vest Africans. SUMMARY
Stibophen in large doses was given to West African soldiers as standard courses of treatment had been found ineffective. Constant electrocardiographic abnormalities were
486
T I l E FI:FI'X!TS (?,!: A N T I . \ t O N Y
ON TIlE
ttEART
recorded and one patient developed a severe ventricular dysrhythmia. treatment docs not appear advisable in W e s t Africans.
S u c h intensive
I),EI;I.'RENCES AZAR, J. E., TABJ~ARA,R. & PIp~4_IN,A. (1951). ~l)aizs. R. ,%c. tro#. 3led. tly~% 45, 383. EDINCTON, (;. M. (1957). W. :lfr. reed. ft., 2, 45. it.au~;(; :MIy~;, ItsIN et al. (1958). Cki~t. mad. J., 76, I(!3. Malxz~:n, F. & Knaus~, M. (1940). 7)'a~ts. R. So~. trop. ~,~led. 1tr,~., 33, 405.