title: Contractile function assessment by intraventricular balloon alters the ability of regional ischaemia to evoke ventricular fibrillation.
abstract: OBJECTIVE
  In drug research using the rat Langendorff heart preparation, it is possible to study left ventricular (LV) contractility using an intraventricular balloon (IVB), and arrhythmogenesis during coronary ligation-induced regional ischaemia. Assessing both concurrently would halve animal requirements. We aimed to test the validity of this approach.
  
  
  METHODS
  The electrocardiogram (ECG) and LV function (IVB) were recorded during regional ischaemia of different extents in a randomized and blinded study.
  
  
  RESULTS
  IVB-induced proarrhythmia was anticipated, but in hearts with an ischaemic zone (IZ) made deliberately small, an inflated IVB reduced ischaemia-induced ventricular fibrillation (VF) incidence as a trend. Repeating studies in hearts with large IZs revealed the effect to be significant. There were no changes in QT interval or other variables that might explain the effect. Insertion of an IVB that was minimally inflated had no effect on any variable compared with 'no IVB' controls. The antiarrhythmic effect of verapamil (a positive control drug) was unaffected by IVB inflation. Removal of an inflated (but not a non-inflated) IVB caused a release of lactate commensurate with reperfusion of an endocardial/subendocardial layer of IVB-induced ischaemia. This was confirmed by intracellular (31) phosphorus ((31) P) nuclear magnetic resonance (NMR) spectroscopy.
  
  
  CONCLUSIONS
  IVB inflation does not inhibit VF suppression by a standard drug, but it has profound antiarrhythmic effects of its own, likely to be due to inflation-induced localized ischaemia. This means rhythm and contractility cannot be assessed concurrently by this approach, with implications for drug discovery and safety assessment.
authors.affiliation: Cardiovascular Division, King's College London, London, UK.
authors.forename: Catherine D E
authors.initials: CD
authors.lastname: Wilder
authors.affiliation: Cardiovascular Division, King's College London, London, UK.
authors.forename: Radwa
authors.initials: R
authors.lastname: Masoud
authors.affiliation: Cardiovascular Division, King's College London, London, UK.
authors.forename: Duygu
authors.initials: D
authors.lastname: Yazar
authors.affiliation: Cardiovascular Division, King's College London, London, UK.
authors.forename: Brett A
authors.initials: BA
authors.lastname: O'Brien
authors.affiliation: Cardiovascular Division, King's College London, London, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Eykyn
authors.affiliation: Cardiovascular Division, King's College London, London, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Curtis
mesh_terms: D000818:Animals; D062906:Cardiac Catheters; D004562:Electrocardiography; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology*; D016277:Ventricular Function, Left; D014700:Verapamil / Q000627:therapeutic use
chemical_list: D010758:Phosphorus; D019344:Lactic Acid; D014700:Verapamil