Ryan B Budde1, Muhammad A Arafat2, Daniel J Pederson2, Thelma A Lovick3, John G R Jefferys4, Pedro P Irazoqui5. 1. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, US. 2. Department of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, US. 3. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, US; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK. 4. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, US; Department of Pharmacology, Oxford University, Oxford, UK; Department of Biochemistry, Oxford University, Oxford, UK. 5. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, US; Department of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, US. Electronic address: pip@purdue.edu.
Abstract
OBJECTIVE: Recent research suggests that obstructive laryngospasm and consequent respiratory arrest may be a mechanism in sudden unexpected death in epilepsy. We sought to test a new hypothesis that this laryngospasm is caused by seizures driving reflux of stomach acid into the larynx, rather than spontaneous pathological activity in the recurrent laryngeal nerve. APPROACH: We used an acute kainic acid model under urethane anesthesia to observe seizure activity in Long-Evans rats. We measured the pH in the esophagus and respiratory activity. In a subset of experiments, we blocked acid movement up the esophagus with a balloon catheter. MAIN RESULTS: In all cases of sudden death, terminal apnea was preceded by a large pH drop from 7 to 2 in the esophagus. In several animals we observed acidic fluid exiting the mouth, sometimes in large quantities. In animals where acid movement was blocked, sudden deaths did not occur. No acid was detected in controls. SIGNIFICANCE: The results suggest that acid movement up the esophagus is a trigger for sudden death in KA induced seizures. The fact that blocking acid also eliminates sudden death implies causation. These results may provide insight to the mechanism of SUDEP in humans.
OBJECTIVE: Recent research suggests that obstructive laryngospasm and consequent respiratory arrest may be a mechanism in sudden unexpected death in epilepsy. We sought to test a new hypothesis that this laryngospasm is caused by seizures driving reflux of stomach acid into the larynx, rather than spontaneous pathological activity in the recurrent laryngeal nerve. APPROACH: We used an acute kainic acid model under urethane anesthesia to observe seizure activity in Long-Evans rats. We measured the pH in the esophagus and respiratory activity. In a subset of experiments, we blocked acid movement up the esophagus with a balloon catheter. MAIN RESULTS: In all cases of sudden death, terminal apnea was preceded by a large pH drop from 7 to 2 in the esophagus. In several animals we observed acidic fluid exiting the mouth, sometimes in large quantities. In animals where acid movement was blocked, sudden deaths did not occur. No acid was detected in controls. SIGNIFICANCE: The results suggest that acid movement up the esophagus is a trigger for sudden death in KA induced seizures. The fact that blocking acid also eliminates sudden death implies causation. These results may provide insight to the mechanism of SUDEP in humans.
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