EFFECT

OF

VAGUS

NERVE

ON C O A G U L A B I L t T Y B.

I.

Kuznik

OF and

V.

STIMULATION

THE

BLOOD

P.

Mishchenko

IN CATS

UDC 612.115-06:612.819.911

E l e c t r i c a l stimulation of the vagus n e r v e in c a t s leads to the d e v e l o p m e n t of h y p e r c o a g u l a tion, a c c o m p a n i e d by an i n c r e a s e in the t h r o m b o p l a s t i c activity of the blood. I n c r e a s e d fib r i n o t o y s i s under these conditions is evidently p r o t e c t i v e in c h a r a c t e r and a i m e d at d i s s o l v ing the clots that m a y be f o r m e d in the blood s t r e a m as a r e s u l t of the d e v e l o p m e n t of h y p e r coagulation. KEY WORDS: vagus nerve; hypercoagulation; fibrinolysis.

Different w o r k e r s have given e x t r e m e l y c o n t r a d i c t o r y accounts of the role of the p a r a s y m p a t h e t i c n e r v o u s s y s t e m in the regulation of h o m e o s t a s i s . W h e r e a s s o m e w o r k e r s [4, 5, 18] c o n s i d e r that excitation of cholinergie s t r u c t u r e s leads to delay of blood clotting, a c c o r d i n g to o t h e r s [2, 10] stimulation of the vagus n e r v e m a y be a c c o m p a n i e d both by quickening and by slowing of blood clotting. In e x p e r i m e n t s on dogs the w r i t e r s showed that vagus n e r v e stimulation, like a d m i n i s t r a t i o n of choline chloride, leads to the d e v e l o p m e n t of hypercoagulation and to i n c r e a s e d f i b r i n o l y s i s [7-9, 12]. The c o n t r a d i c t o r y nature of the data in the l i t e r a t u r e is p r e s u m a b l y explained by the fact that the e x p e r i m e n t s w e r e c a r r i e d out on different animals. To investigate this p r o b l e m e x p e r i m e n t s w e r e p e r f o r m e d in which the vagus n e r v e was stimulated in cats. EXPERIMENTAL

METHOD

E x p e r i m e n t s w e r e e a r r i e d out on 16 c a t s . Under h e x o b a r b i t a l a n e s t h e s i a the vagus n e r v e was e x t e r i o r i z e d in the neck and s t i m u l a t e d by an e l e c t r i c c u r r e n t (frequency 8 / m i n , pulse duration 3 m s e c , strength 5 mA) for 1 h. Blood for investigation was taken a f t e r stimulation for 30 and 60 min and again 30 min a f t e r the end of stimulation of the nerve. The clotting time [17], r e c a l c i f i c a t i o n time [15], p l a s m a heparin t o l e r a n c e [1, 19], p r o t h r o m b i n time (Leningrad B l o o d - T r a n s f u s i o n Institute method), thrombin time, and f r e e heparin [20], the fibrin c o n c e n t r a t i o n [11, 14], the r e t r a c t i o n time [16], and the r e t r a c t i o n of the blood clot and f i b r i n o l y s i s [6] w e r e d e t e r m i n e d in the blood s a m p l e . EXPERIMENTAL In the ening of the and, during tration was (P > 0.05).

RESULTS

e x p e r i m e n t s of s e r i e s I (Table 1) the intact vagus n e r v e was stimulated. This r e s u l t e d in s h o r t blood clotting and p l a s m a r e c a l c i f i c a t i o n t i m e s , an i n c r e a s e in the p l a s m a heparin t o l e r a n c e , the f i r s t 30 rain, a d e c r e a s e in the p r o t h r o m b i n time. A slight d e c r e a s e in the fibrin c o n c e n o b s e r v e d 30 rain a f t e r stimulation but the changes in the o t h e r p a r a m e t e r s w e r e not significant

In three e~periments slowing of blood clotting was observed 60 rain after the beginning of stimulation. However, this reaction developed after preliminary hypereoagulation. D e p a r t m e n t of N o r m a l Physiology, Chita Medical Institute. ( P r e s e n t e d by A c a d e m i c i a n V. N. C h e r n i govskii,) T r a n s l a t e d f r o m Byulleten' E k s p e r i m e n t a l ' n o i Biologii i Meditsiny, Vol. 78, No. 7, pp. 7-9, July, 1974. Original a r t i c l e submitted S e p t e m b e r 18, 1973.

9 1974 Consultants Bureau, a division of Plenum Publishing Corporation, 227 West 17th Street, New York, N. Y. 10011. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission of the publisher. A copy of this article is available from the publisher for $15.00.

723

TABLE 1. Effect of Vagus Nerve Stimulation on Coagulability of the Blood in Cats {M + m) Duringnervestimulation Parameter 'etudied

Control

30 rain

Blood clotting time (in see) plasma mealcification time (in see] prothrombin time fin see) Plasma heparin tolerance (in sec)

178,0 56,0 18,0 182,0

110,02"*-30,0 48,0-'3,2 16,72-,--0,4 120,0"-27,0

Thrombin time (in sec) Free n.eparin {in see) Fibrin (in rag) Retraction time (in rain) Retraction and fibdnolysis (in ~

31,6 8,6 3,7 5~7,0 68,0

31,9-----1,1 9,0m0,7 3,2-"0,5 50,0"+'7,6 72,0"~2,2

60 rain

30 rain af- i

ter ilerve

stimulation

I24,0~29,0 121,0~21,0 48.02+-2,9 46,0~4,9 18,02 1,0 17,4~0.4 107,0~29.0 88,02---34,0 31,721,3 8,820,6 3,6• 47,02+-4,5 72,022,3

3,020,3 5t,02t1,6 65,023,6

In the experiments of s e r i e s II the effect of division of the right vagus nerve on the blood clotting indices was studied. Unilateral division of the vagus nerve in cats had virtually no effect on blood clotting. In the e x p e r i m e n t s of s e r i e s III, after division of the vagus nerve the p e r i p h e r a l end was stimulated electrically. In these experiments shortening of the blood clotting and plasma recalcification times, a dec r e a s e in the prothrombin time, and an increase in the p l a s m a heparin tolerance were observed. The changes found a r e evidence of increased thromboplastic activity of the blood a f t e r stimulation of the p e r i p h e r a l end of the vagus nerve. The r e s u l t s a r e s i m i l a r in many r e s p e c t s with those of the analogous experiments c a r r i e d out by the authors on dogs [8, 12, 13]. The statements in the l i t e r a t u r e that blood clotting in cats is delayed in response to stimulation of the vagus nerve [18] can probably be explained by the development of s e c o n d a r y hypocoagulation in this case, Numerous experiments p e r f o r m e d on different animals in the w r i t e r s ' d e p a r t m e n t have shown that the c o agulability of the blood is always i n c r e a s e d and fibrinolysis intensified initially during excitation of both the sympathetic and the parasympathetic divisions of the autonomic nervous s y s t e m [3, 7-9, 12, 13], These r e sults suggested that p r i m a r y hypocoagulation does not exist in man and higher animals under physiological conditions [7, 8, 12]. Stimulation of the vagus nerve in cats thus leads to a c c e l e r a t i o n of blood clotting. The increased fib r i n o l y s i s in these c a s e s is protective in c h a r a c t e r and is aimed at dissolving the clots that may form in the blood s t r e a m as a result of the development of hypercoagulation. LITERATURE 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

724

CITED

V . P . Baluda, V. N. Malyarovskii, and I. A. Oivin, L a b o r a t o r y Methods of Investigation of the Blood Clotting System [in Russian], Moscow (1962), T . N . Belyavskaya and A. I. Kovaleva, Fiziol. Zh. SSSR, 5.~2, 1315 (1966). V . V . Bochkarnikov, in: The Blood Clotting System and Fibrinolysis [in Russian], Kiev (1969), p. 26. S . A . Georgieva, in: Theoretical and Clinical P r o b l e m s in Blood Coagulation [in Russian], Saratov (1968), p. 25. E . S . Ivanitskii-Vasilenko, in: P r o b l e m s in Nervous Regulation of the Functions of the Animal and Human O r g a n i s m under Normal and Pathological Conditions fin Russian], Chits (1956), p. 21. M . A . Kotevshchikova and B. I. Kuznik, A b s t r a c t s of Proceedings of the Fifth All-Union Conference of L a b o r a t o r y Medical Officers [in Russian], Leningrad (1961), p. 18. B. L Kuznik, in: The Blood Clotting System and Fibrinolysis [in Russian], Kiev (1969), p. 88. B . I . Kuznik, V. V. Al'fonsov, V. P. Mishchenko, et al., P r o b l e m s in N e u r o - H u m o r a l Regulation of Blood Clotting under N o r m a l and Pathological Conditions [in Russian], Chita (1971), p. 73. B . I . Kuznik, V. P. Mishchenko, and V. F. Rusyaev, C o t et Vasa (Prague), 1~1, 146 (1969). A . A . Markosyan, The Physiology of Blood Clotting [in Russian], Moscow (1966). M.S. Machabeli, Clinical P r o b l e m s of Blood Coagulation [in Russian], Tbilisi (1962). V . P . Mishehenko, The Vascular Wall as an Efferent Regulator of Blood Clotting and Fibrinolysis, Doctoral Dissertation [in Russian], Chita (1972). V . P . Mishchenko, B. I. Kuznik, and V. V. Bochkarnikov, C o r e t Vasa (Prague), 14, 223 (1972).

14. 15. 16. 17. 18. 19. 20.

R . A . Rutberg, Lab, Delo, No. 1, 6 (1961). H . D . B e r g e r h o f and L. Roka, Z. Vitamin.-, H o r m o n - , F e r m e n t f o r s c h . , No. 6, 25 (1954). I. Hirschboek, J. Lab. Clin. Med., 38._.,347 (1948). R. Lee and P. White, Am. J. Med. Sci., 14._~5,495 (1913}. F. P l a t t n e r and V. Kodera, Pfliig. Arch. ges. Physiol., 219, 264 (1928). L. P o l l e r , Angiology, 5, 21 (1954). 1~. Sirmai, Probl. Gematol., No. 6, 38 (1957).

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Effect of vagus nerve stimulation on coagulability of the blood in cats.

Electrical stimulation of the vagus nerve in cats leads to the development of hypercoagulation, accompanied by an increase in the thromboplastic activ...
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