title: Hexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.
abstract: OBJECTIVE
  Among 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.
  
  
  METHODS
  Treatment study.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Sprague-Dawley rats.
  
  
  METHODS
  We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Wen-Hsien
authors: WH
authors: Lu
authors: Kai-Sheng
authors: KS
authors: Hsieh
authors: Pei-Jung
authors: PJ
authors: Lu
authors: Yi-Shan
authors: YS
authors: Wu
authors: Wen-Yu
authors: WY
authors: Ho
authors: Chi-Cheng
authors: CC
authors: Lai
authors: Jyh-Seng
authors: JS
authors: Wang
authors: Luo-Ping
authors: LP
authors: Ger
authors: Michael
authors: M
authors: Hsiao
authors: Ching-Jiunn
authors: CJ
authors: Tseng
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D001933:Brain Stem / Q000187:drug effects / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D029821:Enterovirus A, Human / Q000472:pathogenicity; D004769:Enterovirus Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005730:Ganglionic Blockers / Q000008:administration & dosage; D018738:Hexamethonium / Q000008:administration & dosage*; D006973:Hypertension / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate
chemical_list: D002395:Catecholamines; D005730:Ganglionic Blockers; D018738:Hexamethonium