Abstracts

Rationale: Status epilepticus (SE), a period of repeated or prolonged seizure activity, can activate the autonomic nervous system and consequently affect cardiovascular function. Responses of the sympathetic nervous system (SymNS) tend to predominate over parasympathetic nervous system (PsymNS) during SE. This shifts the balance between autonomic divisions (sympathovagal balance) toward SymNS dominance, and therefore increases the risk for cardiac morbidity and mortality. Interestingly, many deaths related to SE often do not occur during or immediately following seizures, but rather in the subsequent days and weeks, and are often associated with cardiac events. Although we previously reported a change in heart rate variability suggesting decreased PsymNS activity 1 week following SE, chronic effects of SE on sympathovagal control of the heart are unknown. Therefore, we tested the hypothesis that SE induces a lasting shift in sympathovagal balance toward SymNS dominance, which diminishes cardiac reflexes, and therefore increases risk of cardiac arrhythmias. Methods: Seizures were induced in male Sprague-Dawley rats using intraperitoneal (i.p.) injections of pilocarpine (30 mg/kg), following LiCl (i.p., 127 mg/kg) and methyl-scopolamine (i.p., 2 mg/kg) pretreatment. Seizures were allowed to continue for 90 min before administration of valproic acid (i.p., 400 mg/kg). Following SE, at 1 or 2 weeks, animals were implanted with femoral venous and arterial catheters, and tested. PsymNS and SymNS tone were evaluated by measuring changes in HR following cardiac autonomic blockade with atropine and/or atenolol. Sympathovagal balance was quantified by comparing basal HR to HR during total autonomic blockade (intrinsic HR). Furthermore, we evaluated baroreflex sensitivity (BRS) and variability in both HR and BP. Results: Sympathovagal balance was shifted toward SymNS dominance at both 1 and 2 weeks following SE. This shift was associated with a decline in intrinsic HR. PsymNS control of HR was decreased following SE. In addition, the operating set point of the baroreflex was increased 1 week following SE, and the maximum bradycardia in response to acute hypertension, which is mediated by PsymNS, was diminished 2 weeks following SE. Finally, blood pressure variability was increased in the high-frequency domain following SE. Conclusions: Autonomic control of HR and BP is chronically altered following SE. First, there is a shift in sympathovagal balance toward SymNS dominance. Second, this shift results from decreased PsymNS activity, with no effect on SymNS tone. Third, reduced PsymNS activity likely contributes to diminished BRS. Fourth, BPV is increased, possibly resulting from decreased baroreflex control. These observations demonstrate how SE has a lasting detrimental effect on autonomic regulation of the heart, characterized by increased SymNS influence and decreased BRS, both of which increase the risk of lethal ventricular arrhythmias. These changes in HR and BP control likely contribute to cardiovascular morbidity and mortality following SE.