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Critical care medicine · May 2013
Comparative StudyHexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.
- Wen-Hsien Lu, Kai-Sheng Hsieh, Pei-Jung Lu, Yi-Shan Wu, Wen-Yu Ho, Chi-Cheng Lai, Jyh-Seng Wang, Luo-Ping Ger, Michael Hsiao, and Ching-Jiunn Tseng.
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
- Crit. Care Med.. 2013 May 1;41(5):1276-85.
ObjectivesAmong enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model.DesignTreatment study.SettingResearch laboratory.SubjectsSprague-Dawley rats.InterventionsWe microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker.Measurements And Main ResultsThe time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours.ConclusionsEarly hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.
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