Abstracts

Rationale: Status epilepticus (SE), a period of repeated or prolonged seizure activity, can lead to a number of cardiopulmonary complications including acute systemic and pulmonary hypertension, tachycardia, pulmonary edema, ventricular arrhythmias, generalized circulatory collapse, and cardiac failure. These complications contribute to an overall mortality of 21-22% in the period (up to several weeks) following SE. Furthermore, the aberrations in cardiac function are suggestive of autonomic dysregulation during and following SE. We propose SE produces an immediate increase in sympathetic nervous system (SymNS) activity that persists for several days and alters normal cardiac function and compensatory reflexes, contributing to morbidity and mortality following SE. Methods: Seizures were induced in male Sprague-Dawley rats using pilocarpine (pilo; 30 mg/kg) following LiCl (127 mg/kg), which continued for 90 min before administration of diazepam (DZ; 10 mg/kg) to diminish seizure activity. Seizures were monitored by direct observation and electroencephalogram (EEG) recordings made from unilateral electrodes placed dorsal to the temporal lobe. Animals recovered for one week before polyethylene catheters were placed in the femoral artery and vein. Arterial pulse pressure recordings were obtained and autonomic input to the heart (SymNS vs. parasympathetic nervous system, PsymNS) was evaluated by estimating heart rate variability (HRV) in both time (interbeat interval, R-R interval, RR) and frequency (low frequency, LF and high frequency, HF) domains. In addition, cardiac contractility was assessed by measuring the mean rate of pressure increase (dP/dt) during contraction. Results: All animals that received pilocarpine had repeated seizure activity, until administration of DZ. The root mean square of the standard deviation of RR intervals (RMSSD, a measure of HRV), was decreased, while both LF and the ratio LF/HF were significantly greater in pilo treated animals compared to control animals. All of these alterations in HRV are indicative of increased cardiac SymNS tone. Additionally, dP/dt was significantly greater in pilo animals.Conclusions: The increase in LF power and LF/HF observed in pilo-treated animals suggests increased SymNS tone one week following SE. Additionally, RMSSD has been previously correlated to PsymNS tone and was diminished in pilo animals. One functional effect of this autonomic difference is increased cardiac contractility observed in pilo treated rats. These data suggest that sympathovagal balance is shifted toward increased SymNS tone within one week following SE, and this has the functional effect of increasing cardiac contractility.