title: Absolute beat-to-beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia-induced ventricular fibrillation.
abstract: OBJECTIVE
  Predicting lethal arrhythmia liability from beat-to-beat variability and instability (BVI) of the ECG intervals is a useful technique in drug assessment. Most investigators use only arrhythmia-free ECGs for this. Recently, it was shown that drug-induced torsades de pointes (TdP) liability can be predicted more accurately from BVI measured irrespective of rhythm, even during arrhythmias (absolute BVI). The present study tested the broader applicability of this assessment by examining whether absolute BVI parameters predict another potential lethal arrhythmia, ischaemia-induced ventricular fibrillation (VF).
  
  
  METHODS
  Langendorff-perfused rat hearts were subjected to regional ischaemia for 15 min. Absolute BVI parameters were derived from ECG intervals measured in 40 consecutive ventricular complexes (irrespective of rhythm) immediately preceding VF onset and compared with time-matched values in hearts not expressing VF.
  
  
  RESULTS
  Increased frequency of non-sinus beats and 'R on T' arrhythmic beats, shortened mean RR and electrical diastolic intervals, and increased BVI of cycle length and repolarization predicted VF occurrence. Absolute BVI parameters that quantify variability of repolarization (e.g. 'short-term variability' of QT interval) had the best predictive power with high sensitivity and specificity. In contrast, VF was not predicted by any BVI parameter derived from the last arrhythmia-free interlude before VF.
  
  
  CONCLUSIONS
  The novel absolute BVI parameters that predicted TdP in rabbit also predict ischaemia-induced VF in rat, indicating a diagnostic and mechanistic congruence. Repolarization inhomogeneity represents a pivotal biomarker of ischaemia-induced VF. The newly validated biomarkers could serve as surrogates for VF in pre-clinical drug investigations.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
authors.forename: Annamária
authors.initials: A
authors.lastname: Sarusi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Rárosi
authors.forename: Mónika
authors.initials: M
authors.lastname: Szűcs
authors.forename: Norbert
authors.initials: N
authors.lastname: Csík
authors.forename: Attila S
authors.initials: AS
authors.lastname: Farkas
authors.forename: Julius Gy
authors.initials: JG
authors.lastname: Papp
authors.forename: András
authors.initials: A
authors.lastname: Varró
authors.forename: Tamás
authors.initials: T
authors.lastname: Forster
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Curtis
authors.forename: András
authors.initials: A
authors.lastname: Farkas
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D010477:Perfusion; D011237:Predictive Value of Tests; D051381:Rats; D012307:Risk Factors; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology
keywords: ECG intervals; Langendorff-perfused rat heart; absolute beat-to-beat variability and instability parameters; ischaemia-induced ventricular fibrillation; repolarization