Effect of orally administrated sodium valproate on alternations in the electrocardiogram of the cat

Subject Areas : Veterinary Clinical Pathology

مهرداد Neshat Gharamaleky ¹ , M.H Khayat Nouri ² , یعقوب Shams Param ³

1 - Department of Clinical Science, Faculty of Veterinary Medicine, Islamic Azad University, Tabriz Branch, Tabriz, Iran
2 - Department of Basic Science, Faculty of Veterinary Medicine, Islamic Azad University, Tabriz Branch, Tabriz, Iran
3 - Graduate of Veterinary Medicine, Faculty of Veterinary Medicine, Islamic Azad University, Tabriz Branch, Tabriz, Iran

Received: 2009-01-19 Accepted : 2009-03-12 Published : 2008-11-21

Keywords: Cat, Sodium valproate, Electrocardiogram,

Abstract :

     Valproic acid is a fatty acid with antiseizure. Currently the salts of valproic acid are used to treat seizure, bipolar disorders and to prevent migraine in human and animals. Valproate sodium inhibits repetitive bursting action potentials of cells. Furthermore it has been shown that high concentrations of valproate can increase potassium transmission across cellular membranes while in low concentrations it can lead to cellular hyperpolarisation. Considering that there are Na+ and K+ channels on the surface of cardiomyocytes, it is probable that sodium valproate can affect these channels as well. Therefore in the present study it was attempted to investigate the effect of orally administered sodium valproate on alterations in the electrocardiogram of the cat. In this experimental study, 8 domestic short hair male cats that were selected randomly were used. valproate sodium was administered orally to all animals at the dose of 50 mg/kg daily for 3 weeks and the electrocardiogram was recorded at days 0 ( prior to drug administration) , 7, 14 and 21 during drug administration in lead II. Heart rate (HR) , P wave duration (PD) , P wave amplitude ( PA) , PR interval (PR- interval), QRS duration( QRS D), R amplitude (RA), ST segment ( ST seg.) and QT interval( QT int.) were evaluated from the electrocardiogram. The results indicate that heart rate and R amplitude(RA) at days 7, 14 and 21 had significantly increased and decreased respectively compared with day 0 (P≤0.05) . These results revealed that valproic acid induces sinus tachycardia in the cat. It is evident from this finding together with the decrease in R wave amplitude that this drug has positive inotropic and negative chronotropic effects and it seems that through these effects it may bring about proarrythmic effect in the cat.  

References:

کاتزونگ و تروور (1377): فارماکولوژی پایه و بالینی کاتزونگ، ترجمه مژدهی آذر و همکاران، انتشارات ارجمند، صفحات: 354-329.

2.       Abdikaliev, N.A., Shabunina, E.V. and Meerson, F.Z. (1989): Elimination of disorders in the electrical stability of the heart during postinfarct cardiosclerosis by using a factor that induces GABA accumulation in the brain. Biull. Eksp. Biol. Med., 107(2): 152-4.

3.       Belkina, L.M., Korchazhkina, N.B., Kamskova, Iu.G. and Fomin, N.A. (1997): The cardioprotective action of the anticonvulsant preparation sodium valproate in disorders of cardiac contractile function caused by acute myocardial infarct in rats. Patol. Fiziol. Eksp. Ter., 2: 18-21.

4. Chong, S.A. and Mahendran, R. (2001): Cardiac effects of psychotropic drugs. Ann. Acad. Med. Singapore, 30(6): 625-31.


5. Gougoux, A. and Vinay, P. (1989): Metabolic effects of valproate on dog renal cortical tubules. Can. J. Physiol. Pharmacol., 67(2): 88-97.


6. Jaffe, R., Leavitt, R. and Wind, T. (2004): QTc prolongation in multiple drug overdoses. J. Clin. Psychopharmacol., 24(3): 348-50.

7.       Jia, H.J., Liu, X., Yan, Y.F. and Ye, Y.W. (1988): Comparison of anti-arrhythmic activities of valproic acid derivatives in animals. Zhongguo Yao Li Xue Bao., 9(1): 37-40.

8. Joseph, R., Calabrese, J.W., Goethe, A., Kayser, D.B., Marcotte, J., et al. (2008): Adverse events in 583 valproate-treated patients. Depression, 3(5): 257-262.


9. Katzung, B.G. (2004): Basic & Clinical Pharmacology. 9^th ed., International Edition, USA, pp: 392-393.


10. Kwon, S., Lee, S., Hyun, M., Choe, B.H., Kim, Y., Park, W. and Cho, Y. (2004): The potential for QT prolongation by antiepileptic drugs in children. Pediatr. Neurol., 30(2): 99-101.


11. Meerson, F.Z., Gimrikh, E.O., Gutsol, L.Ia., Popov, S.V. and Plekhanov, I.G. (1992): The anti-arrhythmic efficacy of sodium valproate. Kardiologiia, 32(7-8): 19-21.


12. Meerson, F.Z., Shabunina, E.V. and Malyshev, IIu. (1988): Direct cardiotropic anti-arrhythmic effect of sodium valproate. Kardiologiia, 28(6): 100-2.

13.    Meyer, S., Kuhlmann, M.K., Peters, F.T., Limbach, H.G. and Lindinger, A. (2005): Severe valproic acid intoxication is associated with atrial tachycardia: secondary detoxication by hemoperfusion. Klin. Padiatr, 217(2): 82-5.

14. Roberts-Thomson, K.C., Teo, K.S. and Young, G.D. (2007): Drug-induced Brugada syndrome with ST-T wave alternans and long QT. Intern. Med. J., 37(3): 199-200.


15. Samhita, P. and Radhakrishnan, K. (2004): Two cases of valproate-induced hyperammonemic encephalopathy without hepatic failure. JAPI, 52: 746-748.

16.    Shabunina, E.V. (1990): The effect of sodium valproate on the electrical stability of the heart in experimental myocardial infarct. Patol. Fiziol. Eksp. Ter., 1: 23-5.

17. Steve, S., Chung, N., Wang, D. and Treiman, M. (2007): Comparative efficacy and safety of antiepileptic drugs for the treatment of status epilepticus. Journal of Pharmacy Practice, 20: 137-146.


18. Thomas, D., Maureen, G., Tremblay, R. and Rodgers, L. (2004): Effects of valproic acid on cardiac metabolism. Can. J. Physiol. Pharmacol., 82(10): 927–933.


19. Triggs, W.J., Gilmore, R.L., Millingtone, D.S., Cibula, J., Bunch, T.S. and Harman, E. (1997): Valproate-associated carnitine deficiency and malignant cerebral edema in the absence of hepatic failure. International Journal of Clinical Pharmacology and Therapeutics, 35(9): 353-356.


20. Venkataraman, V. and Wheless, J.W. (1999): Safety of rapid intravenous infusion of valproate loading doses in epilepsy patients. Epilepsy Res., 35(2): 47-53.


21. Xie, J.T. and Li, C.L. (1992): Induction and termination of after depolarizations and triggered arrhythmias by drugs in cat heart In vivo. Methods Find Exp. Clin. Pharmacol., 14(5): 347-54.