Altered autonomic balance drives the increase in cardiac output and arterial pressure during convulsive seizures in nonanesthetized sheep.

OBJECTIVE

Preclinical and human studies suggest that ictal and interictal modulation of the sympathetic and parasympathetic systems contributes to cardiovascular changes that may induce sudden unexpected death in epilepsy. We therefore investigated the effects of convulsive seizures on cardiovascular and autonomic function in nonanesthetized sheep.

METHODS

Adult female sheep were instrumented to record arterial pressure, heart rate, electroencephalogram, electrocardiogram, and either cardiac output or cardiac and renal sympathetic nerve activity (SNA). Arterial blood samples were collected to assess blood biochemistry. Seizures were induced in nonanesthetized sheep by intravenous infusion of the proconvulsant pentylenetetrazol (PTZ; 5.0 mg/kg/min for 4 min).

RESULTS

PTZ induced consistent generalized tonic-clonic seizures associated with abnormal activity on electroencephalogram. Convulsive seizures increased mean arterial pressure (79.1 ± 4.5 mmHg to 128.5 ± 5.6 mmHg, p < .0001) and cardiac output (4.1 ± .2 to 7.9 ± .5 L/min, p < .0001) at 10 min postseizure; these remained significantly above baseline for 60 min (both n = 12). Heart rate variability decreased (4826.1 ± 766.6 to 210.9 ± 97.7 ms, n = 6, p = .0155) at 10 min and corrected QT interval increased (399 ± 9.1 to 449.7 ± 11 ms, p = .003) at 30 min postictally. Seizures increased cardiac SNA (682 ± 86 to 7558 ± 3955 spikes/min, n = 4, p = .007), whereas renal SNA decreased (4296 ± 784 to 1139 ± 284 spikes/min (p = .047). Seizures decreased blood potassium (3.9 ± .1 to 3.4 ± .1 mmol·L-1, p = .0268) and increased lactate (.68 ± .05 to 12.2 ± 1.39 mmol·L-1; p < .0001).

SIGNIFICANCE: Seizures induced by PTZ in nonanesthetized sheep caused autonomic and cardiovascular disturbances, including postictal tachycardia and arrhythmias, which may contribute to an increased risk of sudden unexpected death in epilepsy.