Atenolol offers better protection than clonidine against cardiac injury in kainic acid‐induced status epilepticus

Abstract

BACKGROUND AND PURPOSEStatus epilepticus is increasingly associated with cardiac injury in both clinical and animal studies. The current study examined ECG activity for up to 48 h following kainic acid (KA) seizure induction and compared the potential of atenolol and clonidine to attenuate this cardiac pathology. EXPERIMENTAL APPROACHSprague-Dawley rats (male, 300-350 g) were implanted with ECG and electrocorticogram electrodes to allow simultaneous telemetric recordings of cardiac and cortical responses during and after KA-induced seizures. Animals were randomized into saline controls, and saline vehicle-, clonidine-or atenolol-pretreated KA groups. KEY RESULTSKA administration in the saline-pretreated group produced an immediate bradycardic response (maximal decrease of 28 ± 6%), coinciding with low-level seizure activity. As high-level seizure behaviours and EEG spiking increased, tachycardia also developed, with a maximum heart rate increase of 38 ± 7% coinciding with QTc prolongation and T wave elevation. Both clonidine and atenolol pretreatment attenuated seizure activity and reduced KA-induced changes in heart rate, QTc interval and T wave amplitude observed during both bradycardic and tachycardic phases in saline-pretreated KA animals. Clonidine, however, failed to reduce the power of EEG frequencies. Atenolol and to a lesser extent clonidine attenuated the cardiac hypercontraction band necrosis, inflammatory infiltration, and oedema at 48 h after KA, relative to the saline-KA group. CONCLUSIONS AND IMPLICATIONSSevere seizure activity in this model was clearly associated with altered ECG activity and cardiac pathology. We suggest that modulation of sympathetic activity by atenolol provides a promising cardioprotective approach in status epilepticus. Abbreviationsb.p.m., beats per minute; HR, heart rate; KA, kainic acid; PSD, power spectral density; SE, status epilepticus; WDS, wet dog shakes BJP British Journal of Pharmacology

Improved cardiac outcomes with combined atenolol and diazepam intervention in seizure

“…Previous work by our group demonstrated that SE resulted in an immediate elevation in sympathetic activity, leading to structural cardiac damage and seizure‐induced cardiomyopathy . Our group also confirmed that pretreatment with sympatholytics could protect the heart during seizure . This current study broadens our understanding by investigating whether intervening in seizure progression with diazepam has any beneficial impact on the associated development of cardiomyopathy in seizure.…”

“…Clinical studies have shown that atenolol is effective at attenuating ischemic damage and improving left ventricular function . Prophylactic atenolol administration has been shown to prevent tachycardia and protect against seizure‐induced QTc prolongation in rat models of SE …”

Early cardiac electrographic and molecular remodeling in a model of status epilepticus and acquired epilepsy

“…8,11 Furthermore, pharmacologic blockade of the β-adrenergic receptors prior to seizure induction have prevented QTc prolongation and T-wave abnormalities, decreased arrhythmogenic potential and myocardial damage, and preserved left ventricular function in SE animals. 32,33 Together, these findings suggest that cardiac sympathetic activation may play a significant role in SE-associated pathologic changes of the myocardium. Indeed, in our study, the SE animals exhibited decreased β1-AR protein levels, a finding that is consistent with adrenergic receptor desensitization due to persistent sympathetic stimulation and a common pathologic alteration in heart failure.…”

Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure

“…Finally, RDN has been demonstrated to attenuate sympathetic outflow via the central nervous system to the heart and other organs 9. It has been reported that noninvasive methods of central sympathetic inhibition, such as clonidine, might have a cardioprotective effect 39. Therefore, this noninvasive method may yield results similar to RDN.…”

“…Therefore, this noninvasive method may yield results similar to RDN. However, it has been considered that high doses of clonidine are required to regulate sympathetic activity and adverse effects (eg, sedation and dry mouth) will be commonly caused 39, 40. Therefore, the effect of RDN might be still better than that in drugs in terms of sympathetic inhibition.…”