title: Increasing glutamate promotes ischemia-reperfusion-induced ventricular arrhythmias in rats in vivo.
abstract: BACKGROUND
  Glutamate mediates cerebral ischemia injury via N-methyl-D-aspartate (NMDA) receptor-coupled ion channels, but the activities of glutamate in the heart remain unclear.
  
  
  OBJECTIVE
  To investigate whether or not glutamate contributes to ischemia- and reperfusion (IR)-induced arrhythmias.
  
  
  METHODS
  Myocardial IR was induced by occlusion of the left anterior descending coronary artery for 30 min and reperfusion for another 30 min. A score system was used to quantify arrhythmias. MK801 (a noncompetitive NMDA receptor antagonist), dihydrokainate (DHK, a glutamate transporter inhibitor) and gabapentin (GBP, a glutamate release inhibitor) were used before ischemia. Serum glutamate levels, Ca(2+)-ATPase activity, SERCA2a protein expression and myocardial mitochondrial Ca(2+) content were assayed.
  
  
  RESULTS
  Myocardial IR caused a significant increase in serum glutamate and high incidences of ventricular arrhythmias. GBP and MK801 significantly ameliorated ventricular arrhythmias, improved SERCA2a expression and sarcoplasmic reticulum Ca(2+)-ATPase activity and reduced Ca(2+) accumulated in mitochondria. By contrast, DHK significantly exacerbated reperfusion-related arrhythmias and mitochondrial Ca(2+) overload while it decreased SERCA2a expression and activity.
  
  
  CONCLUSIONS
  This study showed that glutamate mediates reperfusion arrhythmias, and the corresponding mechanism may be associated with Ca(2+) overload via the NMDA receptor. Reperfusion arrhythmias may be prevented by inhibiting the release of glutamate or by antagonizing NMDA receptors.
authors.affiliation: Department of Cardiology, Anhui Provincial Hospital of Anhui Medical University, Hefei, PR China.
authors.forename: Xianlin
authors.initials: X
authors.lastname: Sun
authors.forename: Jingquan
authors.initials: J
authors.lastname: Zhong
authors.forename: Deguo
authors.initials: D
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Su
authors.forename: Chunsheng
authors.initials: C
authors.lastname: An
authors.forename: Hongjun
authors.initials: H
authors.lastname: Zhu
authors.forename: Ji
authors.initials: J
authors.lastname: Yan
mesh_terms: D000588:Amines / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D000077206:Gabapentin; D018698:Glutamic Acid / Q000097:blood / Q000502:physiology*; D006352:Heart Ventricles / Q000503:physiopathology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; C020889:dihydrokainic acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D016291:Dizocilpine Maleate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D007608:Kainic Acid; D002118:Calcium