title: Increased intraventricular pressures are as harmful as the electrophysiological substrate of heart failure in favoring sustained reentry in the swine heart.
abstract: BACKGROUND
  Heart failure (HF) electrophysiological remodeling (HF-ER) often includes the effect of chronically increased intraventricular pressures (IVPs) and promotes ventricular tachycardia/ventricular fibrillation (VT/VF). In addition, acutely increased IVPs have been associated with a higher rate of VT/VF episodes in chronic HF.
  
  
  OBJECTIVE
  We hypothesized that increased IVPs and/or an ionic-imbalanced (acidified), catecholamine-rich (adrenergic) milieu (AA milieu) may contribute as much as HF-ER to the substrate for reentry in HF. We used a porcine model of tachycardiomyopathy and evaluated the individual/combined contributions of (1) increased IVPs, (2) HF-ER, and (3) an AA milieu.
  
  
  METHODS
  HF-ER was induced in 7 pigs by rapid pacing. Seven pigs were used as controls. Hearts were isolated and Langendorff perfused. Programmed ventricular stimulation was conducted under low or increased IVP and normal/AA milieu (4 combinations). Epicardial optical mapping was used to quantify conduction velocity (CV), action potential duration (APD), and dispersion of repolarization (DoR).
  
  
  RESULTS
  HF-ER decreased CV (-34%; P = .002) and increased APD (11%; P = .024) and DoR (21%; P = .007). Increased IVP amplified DoR (36%; P < .001) and decreased CV (-17%; P = .001) and APD (-8%; P < .001). The AA milieu consistently modified only APD (-9%; P < .001) and led to amplified inter-/intra-subject heterogeneity. Increased IVP similarly raised the odds of inducing sustained VT/VF as the presence of HF-ER (>6-fold).
  
  
  CONCLUSIONS
  By magnifying DoR, decreasing CV, and shortening APD, increased IVP was as harmful as HF-ER in favoring the substrate for sustained reentry in this model. The AA milieu contributed to a much lesser extent. Thus, a stricter control of IVP might be postulated as a useful add-on antiarrhythmic strategy in HF.
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Advanced Development in Arrhythmia Mechanisms and Therapy, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. Electronic address: jgarciaqui.hcsc@salud.madrid.org.
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Quintanilla
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Arrhythmia Unit, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Archondo
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Usandizaga
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Molina-Morúa
authors.affiliation: Experimental Medicine and Surgery Unit, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Cruz
authors.initials: C
authors.lastname: Rodríguez-Bobada
authors.affiliation: Experimental Medicine and Surgery Unit, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: González
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: García-Torrent
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Advanced Development in Arrhythmia Mechanisms and Therapy, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Filgueiras-Rama
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Nicasio
authors.initials: N
authors.lastname: Pérez-Castellano
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit, Cardiovascular Institute, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Pérez-Villacastín
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004562:Electrocardiography; D055724:Electrophysiological Phenomena / Q000502:physiology*; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology*; D017725:Ventricular Pressure / Q000502:physiology*; D020257:Ventricular Remodeling
keywords: Arrhythmias; Heart failure; Optical mapping; Reentry; Remodeling; Stretch