title: Ventricular cycle length irregularity affects the correlation between ventricular rate and coronary flow in isolated, Langendorff perfused guinea pig hearts.
abstract: BACKGROUND
  Heart rate affects coronary flow, but the mechanism is complex. The relationship between rhythm and flow is unclear, especially in experimental settings used for determining drug actions. The present study examined whether ventricular irregularity influences coronary flow independently of heart rate.
  
  
  METHODS
  Guinea pig hearts were perfused (Langendorff mode) at constant pressure. Hypokalemic Krebs solution facilitated spontaneous development of arrhythmias. The ECG, left ventricular and perfusion pressures were recorded, and the coronary flow was measured. Beat-to-beat ventricular cycle length variability was quantified. Hearts were retrospectively allocated to arbitrary 'Low' or 'High' RR variability groups.
  
  
  RESULTS
  A positive linear correlation was found between mean ventricular rate and coronary flow. The slope of the regression line was significantly greater in the 'High' versus 'Low' RR variability group, with greater coronary flow values in the 'High' RR variability group in the physiological heart rate range. During regular rhythm, left ventricular pressure exceeded perfusion pressure and prevented coronary perfusion at peak systole. However, ventricular irregularity significantly increased the number of beats in which left ventricular pressure remained below perfusion pressure, facilitating coronary perfusion.
  
  
  CONCLUSIONS
  In isolated hearts, cycle length irregularity increases the slope of the positive linear correlation between mean ventricular rate and coronary flow via producing beats in which left ventricular pressure remains below perfusion pressure. This means that changes in rhythm have the capacity to influence coronary flow independently of heart rate in isolated hearts perfused at constant pressure, which should be noted in drug studies on arrhythmias performed in Langendorff hearts.
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Hedvig
authors.initials: H
authors.lastname: Takács
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Kui
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Attila S
authors.initials: AS
authors.lastname: Farkas
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Annamária
authors.initials: A
authors.lastname: Sarusi
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Forster
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary; MTA-SZTE Research Group for Cardiovascular Pharmacology, Hungarian Academy of Sciences, Hungary.
authors.forename: Julius Gy
authors.initials: JG
authors.lastname: Papp
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Varró
authors.affiliation: King's College, London, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Curtis
authors.affiliation: King's College, London, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shattock
authors.affiliation: Second Department of Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary. Electronic address: farkas.andras@med.u-szeged.hu.
authors.forename: András
authors.initials: A
authors.lastname: Farkas
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D003326:Coronary Circulation / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000502:physiology*; D006352:Heart Ventricles / Q000503:physiopathology*; D009200:Myocardial Contraction / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D010477:Perfusion / Q000379:methods
keywords: Coronary flow; Guinea pig; Irregular rhythm; Isolated hearts; Langendorff perfusion; Left ventricular pressure; Methods; Perfusion pressure; Ventricular cycle length variability; Ventricular rate