title: Ischemia-reperfusion destabilizes rhythmicity in immature atrioventricular pacemakers: A predisposing factor for postoperative arrhythmias in neonate rabbits.
abstract: Postoperative arrhythmias such as junctional ectopic tachycardia and atrioventricular block are serious postoperative complications for children with congenital heart disease. We hypothesize that ischemia-reperfusion (I/R) related changes exacerbate these postoperative arrhythmias in the neonate heart and administration of postoperative inotropes is contributory.
  
  
  
  The purpose of this study was to study the effects of I/R and postischemic dopamine application on automaticity and rhythmicity in immature and mature pacemaker cells and whole heart preparations.
  
  
  
  Single pacemaker cells and whole heart models of postoperative arrhythmias were generated in a rabbit model encompassing 3 primary risk factors: age, I/R exposure, and dopamine application. Single cells were studied using current clamp and line scan confocal microscopy, whereas whole hearts were studied using optical mapping.
  
  
  
  Four responses were observed in neonatal atrioventricular nodal cells (AVNCs): slowing of AVNC automaticity (from 62±10 to 36 ± 12 action potentials per minute, P<.05); induction of arrhythmicity or increased beat-to-beat variability (0.08 ± 0.04 to 3.83 ± 1.79, P<.05); altered automaticity (subthreshold electrical fluctuations); and disruption of calcium transients. In contrast, these responses were not observed in mature AVNCs or neonatal sinoatrial cells. In whole heart experiments, neonatal hearts experienced persistent postischemia arrhythmias of varying severity, whereas mature hearts exhibited no arrhythmias or relatively transient ones.
  
  
  
  Neonatal pacemaker cells and whole hearts demonstrate a susceptibility to I/R insults resulting in alterations in automaticity, which may predispose neonates to postoperative arrhythmias such as junctional ectopic tachycardia and atrioventricular block.
authors.affiliation: Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Cici
authors.initials: C
authors.lastname: Chenliu
authors.affiliation: Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Pauline
authors.initials: P
authors.lastname: Dan
authors.affiliation: Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Claydon
authors.affiliation: Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Lin
authors.affiliation: Cardiovascular Research Centre CSIC-ICCC, Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Leif
authors.initials: L
authors.lastname: Hove-Madsen
authors.affiliation: Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada; Division of Pediatric Cardiology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Shubhayan
authors.initials: S
authors.lastname: Sanatani
authors.affiliation: Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada. Electronic address: tibbits@sfu.ca.
authors.forename: Glen F
authors.initials: GF
authors.lastname: Tibbits
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D054537:Atrioventricular Block / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D001283:Atrioventricular Node / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006330:Heart Defects, Congenital / Q000503:physiopathology / Q000601:surgery*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D011183:Postoperative Complications / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D011817:Rabbits; D013613:Tachycardia, Ectopic Junctional / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control
keywords: Atrioventricular node; Automaticity; Junctional ectopic tachycardia; Neonate heart; atrioventricular block