The effect of generalized seizure activity on ischemia-induced cardiac arrhythmias and myocardial injury with histopathological evaluation in anesthetized rats

Background/aim: Epileptic seizure leads to sudden unexpected death in epilepsy (SUDEP) among affected patients. The causes of SUDEP are still unclear. The aim of this study was to research the effect of epilepsy on myocardial injury and arrhythmias during experimentally induced acute myocardial ischemia. Materials and methods: Wistar albino rats were divided into four groups: sham, pentylentetrazole (PTZ) + sham, ischemia, and PTZ + ischemia groups. PTZ (65 mg/kg, ip) was given 2 h before ischemia. Seizure scoring was conducted by evaluating the PTZ-induced behavioral changes in the rats. The left main coronary artery was ligated in anesthetized rats for 30 min. The incidence and the number of ventricular arrhythmias were determined. Histopathological scoring was performed for tissue injury by using a microscope. Results: Seizure scores were not different among the groups (P ≻ 0.05). The incidence and number of ventricular tachycardia (VT) episodes were significantly higher in the PTZ + ischemia group than in the ischemia group (P ≻ 0.05). More prominent myocardial damage was observed in the PTZ + ischemia group than in the other groups (histopathological scores: PTZ + ischemia; 2.5 ± 0.5 versus ischemia; 1.2 ± 0.4, P ≺ 0.05). Conclusion: PTZ-induced seizure in rats increased myocardial injury and the incidence and number of VT episodes in myocardial ischemia. These results reveal that seizure in epilepsy patients may increase ventricular arrhythmia and myocardial injury during heart attack.

Keywords:

Epilepsy, pentylentetrazole ventricular arrhythmias, myocardial injury, rat,

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Scorza FA, Cysneiros RM, de Albuquerque M, Scattolini M, Arida RM. Sudden unexpected death in epilepsy: an important concern. Clinics 2011; 66: 65-69.
Nashef L, Walker F, Allen P, Sander JW, Shorvon SD, Fish DR. Apnea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg 1996; 60: 297- 300.
Nei M, Ho RT, Sperling MR. EKG abnormalities during partial seizures in refractory epilepsy. Epilepsia 2000; 41: 542-548.
Janszky I, Hallqvist J, Tomson T, Ahlbom A, Mukamal KJ, Ahnve S. Increased risk and worse prognosis of myocardial infarction in patients with prior hospitalization for epilepsy- the Stockholm Heart Epidemiology Program. Brain 2009; 132: 2798-2804.
Tigaran S, Mølgaard H, McClelland R, Dam M, Jaffe AS. Evidence of cardiac ischemia during seizures in drug refractory epilepsy patients. Neurology 2003; 60: 492-495.
P-Codrea Tigaran S, Dalager-Pedersen S, Baandrup U, Dam M, Vesterby-Charles A. Sudden unexpected death in epilepsy: is death by seizures a cardiac disease? Am J Forensic Med Pathol 2005; 26: 99-105.
Arroja JD, Pignat JM, Sunthorn H, Vulliemoz S. Seizure suspicion; sustained ventricular tachycardia diagnosed by video EEG. Int J Cardiol 2013; 25: 589.
Read MI, Andreianova AA, Harrison JC, Goulton CS, Sammut IA, Kerr DS. Cardiac electrographic and morphological changes following status epilepticus: effect of clonidine. Seizure 2014; 23: 55-61.
Metcalf CS, Poelzing S, Little JG, Bealer SL. Status epilepticus induces cardiac myofilament damage and increased susceptibility to arrhythmias in rats. Am J Physiol Heart Circ Physiol 2009; 297: 2120-2127.
Damasceno DD, Savergnini SQ, Gomes ER, Guatimosim S, Ferreira AJ, Doretto MC, Almeida AP. Cardiac dysfunction in rats prone to audiogenic epileptic seizures. Seizure 2013; 22: 259-266.
Tavares JG, Vasques ER, Arida RM, Cavalheiro EA, Cabral FR, Torres LB, Menezes-Rodrigues FS, Jurkiewicz A, Caricati- Neto A, Godoy CM, Gomes da Silva S. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats. Braz J Med Biol Res 2015; 48: 140-145.
Sahin D, Ilbay G, Imal M, Bozdogan O, Ates N. Vagus nerve stimulation suppresses generalized seizure activity and seizure- triggered postictal cardiac rhythm changes in rats. Physiol Res 2009; 58: 345-350.
Velisek L, Kubova H, Pohl M, Stankova L, Mares P, Schickerova R. Pentylenetetrazol-induced seizures in rats: an ontogenetic study. Naunyn Schmiedebergs Arch Pharmacol 1992; 346: 588- 591.
Goyal SN, Sharma C, Mahajan UB, Patil CR, Agrawal YO, Kumari S, Arya DS, Ojha S. Protective effects of cardamom in isoproterenol-induced myocardial infarction in rats. Int J Mol Sci 2015; 16: 27457-27469.
Gervasi SF, Bianco M, Palmieri V, Cuccaro F, Zeppilli P. QTc interval in adolescents and young athletes: influence of correction formulas. Int J Sports Med 2017; 38: 729-734.
Curtis MJ, Hancox JC, Farkas A, Wainwright CL, Stables CL, Saint DA, Clements-Jewery H, Lambiase PD, Billman GE, Janse MJ, Pugsley MK, Ng GA, Roden DM, Camm AJ, Walker MJ. The Lambeth Conventions (II): guidelines for the study of animal and human ventricular and supraventricular arrhythmias. Pharmacol Ther 2013; 139: 213-248.
Tigaran S, Molgaard H, McClelland R, Dam M, Jaffe AS. Evidence of cardiac ischemia during seizures in drug refractory epilepsy patients. Neurology 2003; 60: 492-495.
Park J, Shin JH, Kim SH, Lim YH, Lee JU, Kim KS, Kim SK, Kim JH, Lim HK, Shin J. Type 2 myocardial infarction following generalized tonic-clonic seizure. Korean Circ J 2011; 41: 681-684.
Farkas A, Curtis MJ. Does QT widening in the Langendorff- perfused rat heart represent the effect of repolarization delay or conduction slowing? J Cardiovasc Pharmacol 2003; 42: 612- 621.
Jansen K, Lagae L. Cardiac changes in epilepsy. Seizure 2010; 19: 455-460.
Kloster R, Engelskjon T. Sudden unexplained death in epilepsy (SUDEP): a clinical perspective and a search for risk factors. J Neurol Neurosurg Psychiatry 1999; 67: 439-444.
Opherk C, Coromilas J, Hirsch LJ. Heart rate and EKG changes in 102 seizures: analysis of influencing factors. Epilepsy Res 2002; 52: 117-127.
Sevcencu C, Struijk JJ. Autonomic alterations and cardiac changes in epilepsy. Epilepsia 2010; 51: 725-737.
Krishnamurthy P, Subramanian V, Singh M, Singh K. β1 integrins modulate β-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling. Hypertension 2007; 49: 865-872.
Nwokocha C, Palacios J, Simirgiotis MJ, Thomas J, Nwokocha M, Young L,Thompson R, Cifuentes F, Paredes A, Delgoda R. Aqueous extract from leaf of Artocarpus altilis provides cardio-protection from isoproterenol induced myocardial damage in rats: negative chronotropic and inotropic effects. J Ethnopharmacol 2017; 203: 163-170.
Jahnel U, Nawrath H, Shieh RC, Sharma VK, Williford DJ, Sheu SS. Modulation of cytosolic free calcium concentration by alpha 1-adrenoceptors in rat atrial cells. Naunyn-Schmiedeberg’s Archives of Pharmacology 1992; 346: 88-93.
Jansen K, Lagae L. Cardiac changes in epilepsy. Seizure 2010; 19: 455-460.
Opherk C, Coromilas J, Hirsch LJ. Heart rate and EKG changes in 102 seizures: analysis of influencing factors. Epilepsy Res 2002; 52: 117-127.
Damasceno DD, Ferreira AJ, Doretto MC, Almeida AP. Cardiovascular dysautonomia after seizures induced by maximal electroshock in Wistar rats. Seizure 2012; 2: 711-716.
Crawford MW, Ho DS, Shams M, Gow R. Magnesium deficiency alters the threshold for epinephrine-induced arrhythmias during halothane or sevoflurane anesthesia in the rat. J Cardiothorac Vasc Anesth 2004; 18: 313-316.
Patterson E, Scherlag BJ, Szabo B, Lazzara R. Facilitation of epinephrine-induced afterdepolarizations by class III antiarrhythmic drugs. J Electrocardiol 1997; 30: 217-224.
Antzelevitch C. Basic mechanisms of reentrant arrhythmias. Curr Opin cardiol 2001; 16: 1-7.
Tristani-Firouzi M. The long and short of it: insights into the short QT syndrome. J Am Coll Cardiol 2014; 63: 1309-1310.
Surges R, Scott CA, Walker MC. Enhanced QT shortening and persistent tachycardia after generalized seizures. Neurology 2010; 74: 421-426.
Tse G, Chan YW, Keung W, Yan BP. Electrophysiological mechanisms of long and short QT syndromes. Int J Cardiol Heart Vasc 2016; 26: 8-13.
Kong L, Wei M, Sun N, Zhu J, Su X. Role of melatonin in calcium overload-induced heart injury. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2017; 28: 611-616.
Baumeister P, Quinn TA. Altered Calcium Handling and Ventricular Arrhythmias in Acute Ischemia. Clin Med Insights Cardiol 2016; 14: 61-69.
Fink M, Noble PJ, Noble D. Ca² + -induced delayed afterdepolarizations are triggered by dyadic subspace Ca² + affirming that increasing SERCA reduces aftercontractions. Am J Physiol Heart Circ Physiol 2011; 301: 921-935.