title: IKs protects from ventricular arrhythmia during cardiac ischemia and reperfusion in rabbits by preserving the repolarization reserve.
abstract: BACKGROUND
  The function of the repolarization reserve in the prevention of ventricular arrhythmias during cardiac ischemia/reperfusion and the impact of ischemia on slowly activated delayed rectifier potassium current (I(Ks)) channel subunit expression are not well understood.
  
  
  RESULTS
  The responses of monophasic action potential duration (MAPD) prolongation and triangulation were investigated following an L-768,673-induced blockade of I(Ks) with or without ischemia/reperfusion in a rabbit model of left circumflex coronary artery occlusion/reperfusion. Ischemia/reperfusion and I(Ks) blockade were found to significantly induce MAPD90 prolongation and increase triangulation at the epicardial zone at 45 min, 60 min, and 75 min after reperfusion, accompanied with an increase in premature ventricular beats (PVBs) during the same period. Additionally, I(Ks) channel subunit expression was examined following transient ischemia or permanent infarction and changes in monophasic action potential (MAP) waveforms challenged by β-adrenergic stimulation were evaluated using a rabbit model of transient or chronic cardiac ischemia. The epicardial MAP in the peri-infarct zone of hearts subjected to infarction for 2 days exhibited increased triangulation under adrenergic stimulation. KCNQ1 protein, the α subunit of the I(Ks) channel, was downregulated in the same group. Both findings were consistent with an increased incidence of PVBs.
  
  
  CONCLUSIONS
  Blockade of I(Ks) caused MAP triangulation, which precipitated ventricular arrhythmias. Chronic ischemia increased the incidence of ventricular arrhythmias under adrenergic stimulation and was associated with increased MAP triangulation of the peri-infarct zone. Downregulation of KCNQ1 protein may be the underlying cause of these changes.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Guo
authors.forename: Xiuren
authors.initials: X
authors.lastname: Gao
authors.forename: Yesong
authors.initials: Y
authors.lastname: Wang
authors.forename: Longyun
authors.initials: L
authors.lastname: Peng
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D001570:Benzodiazepinones / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000473:pathology; D051657:KCNQ1 Potassium Channel / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology; D010496:Pericardium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology; D013997:Time Factors
chemical_list: D000081:Acetamides; D001570:Benzodiazepinones; D051668:Delayed Rectifier Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C109598:L 768673; D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta