Cici Chenliu1, Xiaoye Sheng1, Pauline Dan1, Yang Qu1, Victoria E Claydon2, Eric Lin1, Leif Hove-Madsen3, Shubhayan Sanatani4, Glen F Tibbits5. 1. Cardiovascular Sciences, Child and Family Research Institute, Vancouver, BC, Canada; Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada. 2. Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, BC, Canada. 3. Cardiovascular Research Centre CSIC-ICCC, Hospital de Sant Pau, Barcelona, Spain. 4. 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. 5. 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.
Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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: Lukas Peter Mileder; Nicholas Mark Morris; Stefan Kurath-Koller; Jasmin Pansy; Gerhard Pichler; Mirjam Pocivalnik; Bernhard Schwaberger; Ante Burmas; Berndt Urlesberger Journal: Children (Basel) Date: 2021-05-20