gallop rhythm, dyspnoea and feeble heart sounds which are the classical signs of myocarditis. Myocarditis is not well do- cumented in literature as an important.
INDIAN
PEDIATRICS Volume 6 Number 3 March 1969
Cardiac and Behavioral
Effects of Scorpion
Venom in Experimental
Animals
Purshowtham Rao, G., * Premalatha, and Haranath, P.S.R.K. ****
B.K., ** Venkatakrlshna
scorpions in Kurnool and Cuddapah Districts of Andhra Pradesh are notori .. ously poisonous. Each year nearly 40 to 50 children in the lower age groups die due to scorpion stings as could be seen from the records of Kurnool Medical College Hospital. The children invariably have local pain and swelling at the site of the sting in addition to restlessness, sweating, vomiting, cold extremities and rapid thready pulse. There is fall of blood pressure and tachycardia. All these symptoms are commonly associated with the diagnosis of peripheral circulatory failure. A few children have in .addition gallop rhythm, dyspnoea and feeble heart sounds which are the classical signs of myocarditis. Myocarditis is not well documented in literature as an important cause of death in scorpion stings.
THE
Read at the 5th National Conference of the Indian Academy of Pediatrics at Ahmedabad, January, 1%8.
Bhatt, H***
Only Peon-King 1 makes a definitive point that toxic myocarditis was the important cause of death in his series of cases of scorpion sting in West Indies. The other authors, Grasset+; Waterman 4; Bennett: Brown"; Manson-Baht", give neurotoxicity as the .cause of death. These paradoxical statements made the authors study the effect of scorpion venom administered intravenously in dogs and other animals to detect the role of the toxin on the myocardium, in the hope that once the cause of death is known the patients could get better management. Two types of scorpions are found in these parts. The small, red Buthus tamuIus and the large black Palamneus gravimonus. Of the two, Buthus is more toxic and invariably it is responsible for the children dying of scorpion stings. Hence this scorpion was used in this study on animals.
METHODS "Professor of Pediatrics, Kurnool Medical College, Kurnool , .\P. *'"Assiswnt Professor of Pharmacology, Kurnool The scorpion venom was collected by Medical College. Kurnool AP. ***Assislant- Research Officer. the method described by Deoras-, The ****Proiessor of Pharmacology, Kurnool Medi- . scorpion was held under a glass petri c•.1 college, Kurnool, AP.
95
P. Rao et al
Volume 6 Number 3 \ .
I
was dish with the tail protruding outside . quantities given intraperitone-! ally. into a glass test-tube. A six volt electric shock was given with a D.C. powerpack REsULTS to the last segment (Telson) of the scorpion tail. With each electric shock a few drops of scorpion venom were Out of fifteen dogs injected with ejected and collected in the test-tube. venom only two died. Out of three To each scorpion 4 t05 shocks were rabbits only one died, and out of three given at brief intervals till no more rats only one died. All these animals were observed for a period of four to venom appeared. The weight. of the venom was calculated by weighing the four and half hours after injecting the test-tubes before and after the electric venom. The animals that died did so . shocks. The scorpion venom was diluted within two and half hours. The animals with 0.9% saline and stored in a refrithat received larger doses of· venom gerator. died and those that received smaller doses merely suffered but did not die.. Fifteen dogs of both sexes with weights varying from 6.0 kg to .11.5 kg were This fact was brought out well in the used in these experiments. The dogs dogs. were anaesthetised with pentobarbitone sodium (30 mg/kg) intravenously. Bent EFFEcrs OF INTRA VENOUS INJECTION IN Hypodermic needles ~ere placed sub- ANAESTHETISED DOGS cutaneously into four limbs .and on the precardiac region. They served as elecThe dogs had profuse salivation and trodes to be connection to the electrolacrimation within a few minutes after cardiograph (Siemens Cardiostal Super). intravenous injection of the venom. They Only Standard Lead II was recorded also developed wide pupils. The two throughout. Carotid blood pressure was dogs that died developed almost imrecorded with a mercury manometer. mediately serious ECG changes in addiTracheal respirations were recorded with tion to signs mentioned above. These two dogs developed almost opaque corthe help of a tambour. The right femoral vein was cannulated to facilitate injec- nea, and voided urine frequently and tions. terminally had a large bowel moveThe E.C.G.s were recorded in all the ment. fifteen dogs. But ill only four dogs the blood pressure, and respirations were EFFECT ON .RESPIRATION recorded. The quantity of the venom injected ranged from 35 mgs to 225 mgs. Immediately after injecting the scorpion The two dogs that. died received more venom the respirations increased in rate than 200 mgs of venom, but two other but diminished in amplitude for four to .dogs received 100 and 150 rugs of venom five minutes (Fig 1 ABC). Subseand recovered. The rest eleven dogs quently . there was slowing aud proreceived less than 100 mgs of venom. gressive increase of the amplitude of Scorpion venom was also given in- respirations, till it attained the preinjecttravenously (75 mgs) into the marginal ion height roughly in half an hour's time. ear veins of three .conscious rabbits. In the 1\\'0 dogs that died there was .To three rats, scorpion venom in minute slow progressive decline in amplitude . 96
March,1969
Cardiac and Behavioral Effects of Scorpion Venom:
: :>-. :-.
Fig. 1 (B)
Fig. I (A)
Fig. 1 (C)
EFFECT ON BLOOD PRESSURE:
In the.two dogs that died and received more than two hundred rngms of venom the B.P. fell by about 10 mm immediately on injecting the venom. But within a few seconds the B.P~ started rising and rose by 50 to 60 mms of Hg by about the fifth minute. The B.P. tracing became very irregular : and showed abrupt falls suggestive of cardiac irregularities. In the two other dogs who did not die the B.P. showed a gradual decline after the initial rise which lasted for about 20 to 30 minutes. The B.P. in these dogs fell by an average of 30
mm below the pre injection level. After half an hour the B.P. became steady; Just before killing the.vdogs with pentobarbitone further injection of scorpion venom resulted in the rise of B.P. and depression of respiratory amplitude indicating that these were true actions of the venom and not artifacts. E. C. G.
CHANGES:
With small doses of scorpion venom (35 to 100 mgrns) only sinus tachycardia (Fig: 3) was noticed immediately following the injection of scorpion venom. The sinus trachycardia persisted for 97
Volume 6 Number 3
P. Roo et 01
Fig. 2. Normal (Dog under Pentobarbitone, (Heart Rate 100 P,M.)
Fig. 3 Sinus Tachycardia
(Rate 200 P.M.)
. Fig. 6.
Auriculo-Ventricular conduction, Defects with SiDUSArrest
Fig. 7. S-T Segment Elevation .
..
Fig. 4. Sinus Bradycardia
(Rate 70 P.M.)
Fig. 5. Ventricular Extra systoles with ·Coupling.
Fig. 8.
S-T Segmenf'Depression,
Fig. 9. T-Wave Inversion.
Cardiac and Behavioral Effects of Scorpion Venom
March, 1969
Fig. 10.
Fig.l1.
Bundle Branch Block
Ventricular Fibrillation.
Fig. 12. Ventricular Tachycardia with Tall T -Wave, Suggestive of Myocarditis. I.
about two hours. But in the two dogs on whom E.C.G. was repeated after 48 and 72 hours, even though the dogs appeared clinically perfectly normal, the. E.C.G: showed sinus tachycardia suggesting that the venom was probably still irritating the Sino-Auricular node. In' 'the two dogs injected with 100 and 150 mgms of scorpion venom sinus tachycardia appeared immediately following the injection of venom, but changed over to sinus bradycardia (Fig. 4) in about 10 minutes. The sinus brady cardia was replaced with ventricular extra systoles (Fig. 5) and auriculoventricular conduction defects with sinus arrest (Fig. 6) in about 45 minutes. These changes also reverted to normal in about 4 hours. With higher doses (200 mgms and above) the E.C.G. changes were dra-
matic from the onset and the E.C.G. changes were of greater variety with frequent changes. The initial sinus tachycardia rapidly changed to bradycardia and there were many ventricular extrasystoles (Fig. 5). In addition, changes typical of toxic myocarditis such as S-T segment .. depression (Fig. 8), SoT segment elevation (Fig. 7) and inversion of T-wave (Fig. 9) were noticed. In addition, Bundle Branch Block type of conduction defects (Fig. 10) were also noticed. These changes were ultimately replaced by ventricular fibrillation just before death. (Fig. 11) EFFECT
OF
CONSCIOUS
INTRA VENOUS
VENOM
IN
RABBITS:
All the three rabbits became critically ill as soon as the venom was given intra-
99
P. Rao et al venously. They became quiet and could not move to a painful stimulus. At first they were sitting but within 1- an hour they preferred to lie down though the two thatrsurvived could be made to sit up on giving a forcible stimulus. During this period the rabbits developed wide dilated pupils which were not reacting to light. They salivated profusely and refused to touch food. They frequently voided urine and stools indicating general stress. But roughly after an hour they started improving· and in four hours they became perfectly normal. The third rabbit which had received a larger dose of venom could never get up from the lying posture in about 20 minutes, salivated profusely and developed distension of abdomen and died in half an hour's time. EFFECTS OF INTRAPERITONEAL INJECTION OF VENOM IN CONSCIOUS RATS:
Of the three rats given venoms intraperitoneally only one died within half an hour. All the three rats behaved identical to rabbits and .with similar results. DISCUSSION
These experiments were carried out .firstly to find out if the scorpion venom was lethal to certain experimental animals. This is proved by the death of two dogs, one rabbit and one rat. This experiment also proved that only larger doses of venom kill the animals and that smaller doses make the animal ill. This is similar to the clinical experience in children: The second and important result obtained from the dog experiments was to detect whether there was any effect Onthe myocardium. As WaS mentioned· in the 100
Volume 6 Number 3 introduction it is the common belief of many authorities .5, 6, 7, that the scorpion venom has only neurotoxicity. The pain atthe site of the sting is explained by the local action of the toxin on the nerve endings. The rest of the symptoms are explained by the action on brain-stem nuclei, giving rise to death. Only PoonKing! makes a mention toxicmyocardhis as a cause of death .. The experiments in this series of dogs clearly brings out two points: The first is that smaller doses of venom (less than 100 mgs) produce some changes in B.P, respiration and in E.C.O. The changes were transitory and recovery sets in 3 to 4 hour: Of the two dogs in whom E.C.G. was taken on the 2nd and 3rd day, sinus tachycardia persisted in spite of normal behaviour and clinical normality of these dogs. With very large dose of' venom death occurred within two hours due to toxic myocarditis as was manifested in the E.C.G. by Bundle Branch Block and ventricular fibrillation. These two dogs also developed progressively smaller respiratory amplitude (? central) and fall of B.P. In other two dogs receiving medium size dose of venom similar respiratory and B.P. changes were noticed, but ventricular fibrillation and heart block was not noticed on the E.C.G. indicating that these two E.C.G. changes are probably not reversible and indicate to grave prognosis.
of
SUMMARY
The red scorpion venom was injected intravenously into fifteen dogs, three rabbits and intraperitoneally into three rats. Inthe two dogs, that died E.C.G. showed changes typical of toxic myocarditis which was probably the cause of death. The B.P. and the respiratory amplitude also fell in these dogs. The
March, 1969
Cardiac and Behavioral Effects of Scorpion Venom
.
two dogs that received smaller doses of venom had somewhat similar changes in B. P. and respiration. The E. C. G. changes were somewhat similar except that Bundle Branch Block and ventricular fibrillation was absent. Eleven dogs which had. received much smaller quantities of venom showed only sinus tachycardia. The rabbits and the rats also demonstrated that larger dose of venom is . lethal and the smaller doses only produce illness.
REFERENCES 1. Peon-King, T.: Brit. M. J., 1: 374, 1963. 2. Deoras,P.
J.: J. Uni. Bombay, 29: 1961.
3. Grasset, E. et al: Trans. Roy. Soc. Trap. Med. Hyg., 39: 397, 1946. 4. Waterman, J. A.: Ibid., 31: 607, 1938. 5. Bennet. I. L.: "Principles ofintemal medicine" 3rd edition, Edited by T. B. Harrison et alChapter 205, Me Graw-Hill, New York, 1958. 6. Brown H. W.: "Text Book of Medicine" 10th edition. Edited by Cecil & Loeb. P.414, Saundars Philadelphia, 1959. . 7. Manson-Bahr P: "Tropical diseases" edition, 831, Cassel, London, 1961.
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