Valproic acid: Does it have an antiarrhythmic action?

Year 2013, Volume: 38 Issue: 4, 592 - 600, 01.12.2013

Osama Shukir Muhammed Amin Ali Mahmood

Abstract

Objective: The antiepileptic sodium valproate (valproic acid; VPA) is thought to possess an antiarrhythmic action. We aimed to explore whether this medication influences cardiac atrial ectopics or not. Methods: From December 1, 2009 to June 1, 2011, 80 consecutive patients who were newly diagnosed with cryptogenic generalized tonic-clonic seizures were enrolled in this prospective short-term longitudinal observational study, which was conducted at the Sulaimaniya General Teaching Hospital, Iraq. Forty patients were allocated to receive VPA and the rest (n=40) were given placebo. All patients underwent cardiac 24-hour Holter monitoring before and after one week of VPA or placebo administration. The minimum heart rate (MiHR) and maximum heart rate (MxHR) as well as the total number of atrial ectopics (TNAE) were evaluated. Results: VPA significantly reduced the MiHR, MxHR, and the TNAE. In the placebo group, the reduction in the MiHR was statistically significant while the reduction in the MxHR and the TNAE were not. However, the reduction in the target parameters in the VPA-treated group did not demonstrate a dose-dependent effect. When both groups were evaluated head-to-head for the reduction in the MiHR before and after week of therapy, there was no statistically significant difference between them. Conclusion: Sodium valproate therapy appears to be effective against atrial ectopic beats and may be used as an antiarrhythmic medication in patients who co-experience seizures and troublesome atrial ectopics.

Keywords

valproic acid; Holter monitoring; atrial ectopic; seizure

Valproik Asit Aritmiye Yol Açar mı?

Abstract

Amaç : Antiepileptik olan sodyum valproat (valproik asit: VPA) ın anti aritmik bir etkiye de sahip olduğu düşünülmektedir. Bu çalışmanın amacı VPA"ın ektopik kardiak aritmi tedavisi üzerine etkisinin olup olamadığını araştırmaktır. Materyal-Metod: 1 Aralık 2009 ile 1 Haziran 2011 tarihlerini kapsayan çalışmamızda kriptojenik generalize tonik klonik nöbet tanısı almış 80 hasta prospektif bir çalışmayla gözlemlenmiştir. Bu çalışma Irak Sulaimaniya Genel Eğitim Hastenesinde yapılmıştır. Kırk hastaya VPA verilirken ve geri kalan 40 hastaya plasebo verildi. VPA uygulaması başlamadan 1 hafta öncesinden başlayarak ve 1 hafta sonrasına kadar tüm hastalar 24 saat boyunca kardiyak holter ile gözlemlenmiştir. Minumum kalp hızı oranı (MiHR) ve maksimum kalp hızı oranı (MxHR) ile total ektopik atrial aritmi sayıları (TNAE) değerlendirildi. Bulgular: VPA nın MiRH, MxRH ve TNAE yi önemli derecede azalttığı görülmüştür. Plasebo grubunda; MiHR grubundaki azalma istatistiksel olarak anlamlı iken MxRH ve TNAE gruplarındaki azalma anlamlı değildi. Ancak VPA ile tedavi edilen grupta görülen azalma doza bağımlı bir etki oluşturmamıştır. Terapiden 1 hafta öncesinde ve sonrasında yapılan değerlendirmede iki grup arasındaki MiHR azalma oranı istatistiksel olarak bir farklılık göstermemiştir. Sonuç: Sodyum valproat tedavisinin atrial ektopik atımlara etkili olduğu görülmektedir, dolayısıyla ektopik aritmi ve nöbet görülen hastalarda antiaritmitik olarak VPA"nın kullanılabileceği düşünülmektedir.

Keywords

Sodyum valproat, holter ile gözlem, atrial ektopi, nöbet.

References

• Scollo-Lavizzari G, Proeckl D.Sodium valproate-still a current antiepileptic agent?. Praxis 1994;83:1098
• Agrawal RP, Goswami J, Jain S, et al. Management of diabetic neuropathy by sodium valproate and glyceryl trinitrate spray: a prospective double-blind randomized placebo-controlled study. Diabetes Res Clin Pract. 2009;83:371-8.
• Spasic M, Zivkovic M, Lukic H. Prophylactic treatment of migraine with valproate. Med Biol 2003;10: 106-10.
• El-Mallakh RS, Huff MO. Mood stabilizers and ion regulation. Harv Rev Psychiatry 2001; 9: 23-32.
• Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience. CNS Drugs. 2002; 16:695-714.
• Meerson FZ, Shabunina EV, Malyshev IIu. Direct cardiotropic anti-arrhythmic effect of sodium valproate. Kardiologiia. 1988; 28:100-2.
• Meerson FZ, Gimrikh EO, Gutsol LIa, et al. The antiarrhythmic efficacy of sodium valproate. Kardiologiia. 1992; 32:19-21.
• Ding BC, Gao ZY, Wu M, et al. Comparison of effects of magnesium valproate and sodium valproate on the action potential of isolated papillary muscle from guinea pigs and dogs. J Tongji Med Univ. 1990; 10:248-52.
• McNamara JO. Drugs effective in the therapy of the epilepsies. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG (Eds.) Goodman & Gilman's The pharmacological basis of therapeutics, 9th edition. New York: McGraw-Hill. 1996; 476.
• Pousti A, Zare Jahromi A, Malihi G, et al. Effect of sodium valproate on ouabain-induced arrhythmia in isolated Guinea pig atria. Ira J Pharm Therap. 2007; 6:41Shabunina EV. [The effect of sodium valproate on the electrical stability of the heart in experimental myocardial infarct]. Patol Fiziol Eksp Ter. 1990; 23-5.
• Bowes AJ, Khan MI, Shi Y, et al. Valproate attenuates accelerated atherosclerosis in hyperglycemic apoE-deficient mice: evidence in support of a role for endoplasmic reticulum stress and glycogen synthase kinase-3 in lesion development and hepatic steatosis. Am J Pathol. 2009; 174:330-42.
• Fedorov VV, Glukhov AV, Ambrosi CM, et al. Effects of K(ATP) channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts. J Mol Cell Cardiol. 2011; 51: 215-25.
• Brodsky M, Wu D, Denes P, et al. Arrhythmias documented by 24 hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol. 1977; 39:390-5.
• Folarin VA, Fitzsimmons PJ, Kruyer WB. Holter monitor findings in asymptomatic male military aviators without structural heart disease. Aviat Space Environ Med. 2001; 72:836-8.
• Dionne MV, Kruyer WB, Snyder QC Jr. Results of Holter monitoring U.S. Air Force aircrew with ectopy on 12-lead electrocardiograms. Aviat Space Environ Med. 2000;71:1190-6.
• Lopinto-Khoury C, Mintzer S. Antiepileptic drugs and markers of vascular risk. Curr Treat Options Neurol 2010; 12:300-8.
• Andersen GO, Ritland S. Life threatening intoxication with sodium valproate. J Toxicol Clin Toxicol. 1995; 33:279-84.
• Sidorenko GI. Neurocirculatory dystonia (does this disease exist?). Kardiologiia. 2003; 43:93-8.
• Yazışma Adresi / Address for Correspondence: Dr. Osama Shukir Muhammed Amin Sulaimaniya Post-Office, PO BOX 196, Sulaimaniya City, Iraq E-mail: [e-mail]. geliş tarihi/received :20.02.2013 kabul tarihi/accepted:25.03.2013