The role of hypoventilation in a sheep model of epileptic sudden death

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Johnston SC, Horn JK, Valente J, and Simon RP (1995) The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 37:4 531–7.

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Abstract: Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.

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  • Study of induced seizures in sheep, with sudden death occurring in some animals. Arrhythmias were observed in animals who died as well as in those who survived. Pulmonary edema also was not signifcantly different between the two groups. Central apnea was seen in the animals who died but not those who survived. A similar mechanism could be at work in SUDEP, but it is difficult to translate this status epilepticus model to patient deaths that occur without seizure. In R.P. Simon 1997 there was also an increase in pulmonary artery and left atrial pressures with the sheep suffering from SUDEP. Another study conducted by Johnston et al found with seizure induction there was a increase in hypercarbia, hypoxia, and irregular breathing associated with the seizures, however reason for death is not fully clear.

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