Tzekov, Tz.

Uzunova, A.

English

Varna Medical University Press: Journals

ELECTROCARDIOGRAPHIC CHANGES IN EXPERIMENTAL MYOCARDITIS AND ARTHRITIS IN NEONATALLY THYMECTOMIZED RATSTz. Tzekov, A. UzunovaBy now the etiological role of streptococci in rheumatism is beyond any doubt but its pathogenesis notwithstanding the intense experimental stu-dies in course remains as yet unclarified. According to Bibikova and co-workers (1965) and Borisova (1967) allergy of the delayed (cellular) type is more characteristic of rheumatism than that of the early (rapid) form of allergy, under which heading it is classified by Cripe and assoc. (1966).Arnasan and assoc. (1962 a, b; 1964), Jankovic and assoc. (1962) and Waks- man and assoc. (1964) have demonstrated that neonatal thymectomy inhi-bits the reactions of hypersensitivity of delayed (cellular) type. According to Paul Kallos (1963) the study of the thymus is of interest not only for immunobiology in the strict sense of the word, but also for the better under-standing of allergic and autoimmune phenomena. This gives us sufficient ground to assume that the thymus as an immune reactivity organ is related also to the pathogenesis of rheumatism. Neonatal thymectomy which inhi-bits the reactions of hypersensitivity of delayed (cellular) type would sup-press the development of allergy of delayed type in rheumatism.It is known that the course run by rheumatism in humans and also expe-rimental myocarditis in animals, is accompanied in most of the cases by a change in electrocardiographic data. Hence the EC'G study appears to be one of the reliable indices for the activity of experimentally induced myo-carditis.The purpose of the present study is to carry out a comparative ECG in-vestigation on neonatally thymectomized and intact white rats with expe-rimentally induced myocarditis.fMaterial and MethodThe experiments were carried out on white rats Wistar breed of both sexes divided into two groups: a control one composed of 28 animals and experimental one — thirty one.In the animals of the control group thymectomy through aspiration was performed 24—48 hours after the birth.Experimental myocarditis was produced in both groups of animals upon completing of the age of three months according to the method deve-loped at the Chair of Pathophysiology — VMI, Varna. Intravenous inject-80 Tz. Tzekov, A. Uzunova 2ions were made three times at two-week intervals of 0,2 ml 1000 million suspension per ml of 24-hour culture fi-hemolytic streptococci group A.The initial electrocardiograms were made three days prior to the first administration of streptococci. In order to follow-up the dynamic process the subsequent ECG investigations were made on the fifth day after each streptococcus suspension injection. The rats were fixed in prone position over a wooden rack isolated by rubber padding. The elctrocardiographic recordings were made on unasthetized animals according to a method adopt-ed in the Chair of Pathophysiology — Higher Medical Institute (VMI), Varna (Z. Kemileva andassoc., 1963). Electrocardiograph PST 3 S300 Schwar- zer was employed at amplification 1 mV/cm and velocity of paper 100 mm/sec which enabled the obtaining of a clearcut recording of the P wave the in-terval ST and the T wave. The upper right and left limbs were recorded electrocardiographically on the first channel, the upper right and lower left — on the second channel and the upper left and lower left limbs — on the third channel.Results and DiscussionThe initial electrocardiograms of both animal groups — not thymec- tomized and thymectomized — reveal the following characteristic features. The average heart rate is 510 beats per minute (from 450 to 631) in not thy-mectomized and 512 beat/min (from 459 to 599) in the thymectomized ani-mals. The P wave in most of the cases of both groups is isoelectric or hardly discernible in the first lead. In the remaining two leads it is invariably po-sitive and tapered with average duration in the non-thymectomized ani-mals 0,013 sec and in the thymectomized — 0,0126 seconds. The average P2 height in the non-thymectomized rats is 1,74 mm and P3 — 1,14 mm. In the thymectomized the average height of P2 and P3 is 1,41 mm and 1,02 mm respectively. The PQ interval for the non-thymectomized animals ave-rages 0,037 sec, and for the thymectomized 0,036 seconds (shorter than the interval value given by Kemileva and Vasilev — 0,045 sec, and by Bosh- kov and co-workers — 0,04 sec). The Q wave in all three leads in most ca-ses was not recorded and that is why its starting values are not reported in the paper. The QRS complex averaged 0,0165 sec in the non-thymectomized rats and 0,0173 sec in the thymectomized group (according to Kemileia and Vassilev, the average duration is 0,019 sec). The average duration of the R wave in the non-thymectomized rats is as follows: R1 — 0,0095 sec, R„ — 0,0094 sec and R3 — 0,0096 sec. In the thymectomized animals the data obtained show 0,0097 sec for Rx, 0,0096 sec — for R, and 0,0097 sec — for R3. The height of the same wave in the group of unoperated rats averages 5,10 mm for R1( 8,40 mm for R2 and 4,50 mm for R3 whereas in the thymec-tomized, the height of R2 averages 3,62 mm, R2 — 6,72 mm and R3 — 3,40 mm. The figures just cited are higher than those reported by Kemi-leia and 1 assilev (R2 — 2,51 mm, R, — 5,9 mm and R3 — 4,9 mm) and by Lepeshin (R2 — 4,6 mm). The duration of the S wave in the non-thymec- tomized animals is on the average 0,0067 sec for Sj, 0,0063 sec for S2 and 0,0058 sec for S3. In the thymectomized animals the average duration of the S wave in the three leads is respectively 0,0075, 0,0074 and 0,0074 seconds. The3 Electrocardiographic changes in experimental. . 81depth of this same wave averaged 2,14 mm for S,, 3,24 mm for S2 and 2,66 for S3 and for the thymectomized animals respectively — 2,06 mm, 4,32 mm and 2,40 mm for the first, second and third leads. The terminal part of the electrocardiographic complex is set on a wide base with average duration in the intact rats 0,056 sec and in the thymectomized rats — 0,058 seconds. The T wa\Ie is rounded. Its average duration in non-thymectomized rats is 0,049 sec, and in the thymectomized — 0,051 seconds. The height of the same wave in the first lead in both animal groups is either isoelectric or hard to detect. In the second and third lead in the group of non-thymecio- mized animals it is accordingly 2,01 mm for T2 and 1,51 mm T3 and in the thymectomized — 1,48 mm for T2 and 0,88 mm for T3.The results of the ECG investigation after each single injection of 6-hemolytic streptococci, group A, are presented in Table 1. The patholo-gic changes are classified in two degrees: first and second. The first degree includes slighter deviations from the normal value — decrease of P, R and T wave to 40% of the starting level, slight elongation of PQ without other pathological alternations. The second degree electrocardiograms dis-play a decrease of the T wave exceeding with 50% the starting level, sub-stantial fall of the P and R waves, manifested by changes in both leads and conductivity impairment.T a b l e  IStreptococciinjection ECGCONTROLS0/0THYMECTOMIZEDAfter the first unchanged 19,00 41,17I degree 57,14 52,94II degree 23,86 5,81After the second unchanged 7,14 41,17I degree 50,00 52,94II degree 42,86 5,81After the third unchanged — 20,00I degree 23,81 40,00II degree 76,19 40,00It is evident from the table that the ECG changes in the thymectomized animals show interesting dynamics as compared to that of non-thymecto-mized control rats. Following the first injection of streptococci 19% of the non-thymectomized rats show no deviations whatsoever from the initial electrocardiograms the same percentage for the thymectomized being 41,17, i. e. twice as higher. The percentage of changes of I degree is approxi-mately equal whereas the percentage of II degree changes in non-thymecto-mized animals is 23.86 and in thymectomized — only 5,81. Following the secondary streptococci introduction this percentage in the non-thymecto-mized rats augments up to 42,86 whilst in the thymectomized it is main-tained unaltered — 5,81. After the thrid injection all non-thymectomized animals disclose ECG data characteristic of myocardial impairment. In6 Scripta scientiflea medico82 Tz. Tzekov, A. Uzunova 420°o of the thymectomized animals there were no changes whatsoever. The pathological ECG changes of II degree in the control, non-thymectomized animals amounts to 76,91 °o and in the group of thymectomized — 40,0%,i. e. almost twice as less.The statistical elaboration of the data regarding the changes in the indi-vidual teeth and sections of the electrocardiograms confirmed the reliabi-lity of the weaker affection of thymectomized animals as compared to non- thymectomized. In the latter group the lowering of the P, R and T waves is much greater and statistically reliable. Moreover in the thymectomized rats except for the R2 wave after the third injection of streptococci, it is not altered in the remaining leads after the first and second injection.The changes in the P and T waves are still more conspicuous and after the three streptococcal injections the lesults are statistically reliable. The P2 tooth in the controls (non-thymectomized) rats is reduced after the I, II and III injection respectively by 28,5%, 23,5%) and 35,2% from the ini-tial level whilst P2 in the thymectomized animals after the I and II inject-ion is reduced respectively by 12,7% and 8,9%> and is maintained at the same level — 18,9% — after the third injection. Much more striking are the results in the T wave. Thus for instance, T2 of the non-thymectomized rats is reduced after I, II and III injection of streptococci by 27,9%, 35,9% and 53,7%, whereas in the thymectomized after identical injections, it is reduced by 20°o, 34,6% and 37,3%. The same holds true for T3 where the reduction of the wave after the third injection amounts to 50°n, whereas T;, in the thymectomized rats is reduced after the same injection merely by 27,0% i. e. almost twice as less.The comparative study of electricardiographic changes and pathological data concerning myocardial impairment is of utmost interest and it will be discussed in a separate publication. In 85,7% of the control non-thy-mectomized animals, inflammatory changes in the myocardium were esta-blished in the course of pathohistological and histochemical investigations whilst in the group of thymectomized — 48,4%. Such a comparison indi-cates that 14,3% of the electrocardiographic changes in non-thymectomized rats are rather slight, promptly subsiding and lacking appropriate morpholo-gical substrate. Among the thymectomized animals the percentage of slight pathological ECG deflections is substantially higher — amounting to 40,0 per cent. The percentage of 11 degree changes in the same animals — 40,0% — virtually coincides with the percentage of the inflammatory changes in the myocardium, established during pathohistological investigation — 48,4 per cent.The ECG data established in the study of animals with experimentally induced myocarditis demonstrate a marked heavier affection of non-thy-mectomized animals as compared to those thymectomized.In all likelihood, neonatal thymectomy inhibits the development of allergic reaction of delayed (cellular) type which lies at the base of the myo-cardial lesions in experimental myocarditis and rheumatism in humans.There is some difference between the initial ECG data in thymectomized and non-thymectomized rats, but the extent to which thymectomy influ-ences the electrocardiogram will be the subject of further investigations.5 Electrocardiographic changes in experimental. . . 8 3R E F E R E N C E S1. Б и б и к o и a,  T. И. .  A.  M. Б о р и с о в  a. C. C. M у т и и, Я. A. C и-т и д и и. Опит дальнейшего изучения аллергии замедленного типа при рев- матизме. Современпие нроблемм ревматологии, ред. Е. М. Тареев, «Медицина», М., 19^5, 5 6 -6 1 .2. Б о ж к о в ,  Б. ,  С т. М и л а н о в ,  С т. Щ е р е в ,  X р. М а р и н о в .  Елек-грокарднографически изследвания при експериментален миокардит у плъхове, получен по различни методи. Експ. мед. и морф., 1965, 1, 53—60.3. Б о р и с о  в а, А. М. Некоторие итогн изучения аллергии замедленного типапри ревмагнзме. Вопр. ревмат., 1967, 3, 61—66.4. К е м и л е в а, 3 д р., Й. В а с и л е в .  ЕКГ изследвания на нормални и епн-нефректомирапи плъхове. Трудоче на ВМИ  — Варна, IV, 1965, 1, 56—97.5. К р а й  и, Л. Клиннческая нммунология и аллергия. Перевод с английското,«Медицина», М., 1966, 298.6. A r n a s o n ,  В. G.. В. D. .1 a n k о v i с, В. Н. W a k s m a n. Effect ofthymectomy on «delayed» hypersensitive reactions. Nature, 1962, 194, 99.7. A r n a s o n ,  B.  G. ,  B.  D.  J a n k o v i c, В.  H.  W a k s m a n, C. W e n-n e r s t e n .  Role of the thymus in immune reactions in rats. 11. Supressive ef-fects of thymectomy at birth on reactions of delayed (cellular) hypersensitivity and the circulating small lymphocyte. J. Exp. Med., 116, 177, 962.8 A r n a s o n ,  B. ,  D.  J a n k o v i c, В.  H.  W a k s m a n .  Role of the thymusin immune reactions in rats. In The thymus in immunobiology. R. A. Good andA. E. Gabrielsen. Eds., 492, Hoeber-Harper, New York 1964.!1. P a u l  K a 11 o s. Die Biologie des Thy mus nach dem heutigen Stande der For- schung.vonJ. F. G. P. Miller and P. Duker, S. Karger, Basel—New York, 1964, Vorwort.10. W a k s m a n, В. H. Sensitization reactions in thymectomized animals. In «The Thymus», edited by D. Metcalf and V. Defendi. Philadelphia, Wistar Inst. Press, W'ister Inst. Monogr., 1964. 2, 95.ЗЛЕКТР0КАРДИ0ГРАФИЧЕСКИЕ ИЗМЕНЕНИЯ ПРИ ЗКСПЕРИМЕНТАЛЬНОММИОКАРДИТЕ И АРТРИТЕ У НЕОНАТАЛЬНО ТИМЗКТОМИРОВАНН Ь1ХКРЬ1СЦ. Цеков, А . Узунова Р Е З Ю М ЕАвтори ставят перед собой цель пронзвестн сравнительное злектрокарднографи- ческое нзучение у н е о и а т а л ь н о  тнмзктомнрованннх и интактних белих крие с зкепе- риментальпо визванним миокарднтом по методу, разработанном в Кафедре патоло- гическон физиологии ВМИ города Варни.При записи злектрокарднограмми пспользован поликардиоскриит Шварцер», со скоростно движения бумагн 100 мм сек, что позволило получить более отчетлнвие зубец Р. растоянне ST н зубец Т.Изменения разделени на две степени — первучо и вторую. ЕКГ данние указивают на более тяжелое поражение нетнмзктомпровпнних животних п после трех введений стрептококковой суспеиснн. После третьего введения все нетимзктомпрованние жи- Honiue дали ЕКГ-пзмеиения и то в 76,19% П-ой степени, в то время как тнмзктоми- рованние в 20% случаев не дали измененин и только 40% дали изменения П-ой сте-пени.Представляет интерес сопоставление ЗКГ-данних с даниими патохистологиче- ского исследования на поражение миокарда. Из нетнмзктомированних животних у 85,7% били на лицо воспалительние изменения в миокарде, в то время как такие изменения у тимзктомпровапних животних наблюдалисъ только у 48,4%.ЗКГ-данние подтверждают вероятность, что неонатальная тимзктомия подавляет развитие аллергической реакции поздиего (клеточного) типа, которая лежит в основе миокардних пораженнй при зкепернментальном миокардите и ревматизме у человека.

ELECTROCARDIOGRAPHIC CHANGES IN EXPERIMENTAL MYOCARDITIS AND ARTHRITIS IN NEONATALLY THYMECTOMIZED RATS

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ELECTROCARDIOGRAPHIC CHANGES IN EXPERIMENTAL MYOCARDITIS AND ARTHRITIS IN NEONATALLY THYMECTOMIZED RATS

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