Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death

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Johnston SC, Siedenberg R, Min JK, Jerome EH, and Laxer KD (1997) Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol 42:4 588–94.

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Abstract: The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and central hypoventilation could not be determined because airway flow and respiratory effort were not monitored. In this study, status epilepticus was induced in unsedated sheep with tracheostomies monitored by electrocardiography, electroencephalography, arterial line, serial blood gases, and airway flowmeter. All 8 animals demonstrated central apnea and hypoventilation, which resulted in the death of 1 and contributed to the death of another. A third animal died of acute heart failure within 2 minutes of seizure onset, accompanied by a large septal myocardial hemorrhage, contraction bands, and signs of global cardiac ischemia. More subtle contraction bands, subendocardial hemorrhage, and signs of acute myocardial ischemia were seen in other animals as well, none of which died of cardiac causes. Malignant arrhythmia was not seen in any of the sheep. Central hypoventilation and apnea accompany generalized status epilepticus and may be an important cause of sudden death in epileptics. Acute cardiac failure may also be a cause of epileptic sudden death.


  • Periods of central apnea were seen in all cases, though the duration varied widely. Apnea was always present during the tonic segment and sometimes occurred later. Minute ventilation increased but hypercapnia was still seen. Overall conclusions are a bit unclear; 3 animals died during the experiment, but the causes of death were different for each of the three. It is unclear whether authors favor central apnea or pulmonary edema as the cause of death in their system. They propose the following model seizures → sympathetic overactivity → cardiac ischemia and contraction bands → left atrial hypertension → pulmonary endothelial cell injury → acute pulmonary edema but discuss central apnea repeatedly throughout the article.