Temperature modulation of ventricular arrhythmogenicity in a canine tissue model of Brugada syndrome

Hiroshi Morita, Douglas P. Zipes, Shiho T. Morita, Jiashin Wu

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


Background: Fever promotes ventricular arrhythmias in Brugada syndrome (BrS). Hypothermia can induce BrS electrocardiogram (ECG) and arrhythmia. However, the mechanisms are unclear. Objective: We evaluated the hypothesis that pathological temperatures promoted arrhythmogenesis by modulating the spatial heterogeneity and functional dynamics of right ventricular electrophysiological activity. Methods: We mapped action potentials (APs) on the epicardial or cut-exposed transmural surfaces and recorded transmural ECGs in 27 arterially perfused canine right ventricular preparations before and after inducing BrS at 32°C, 36.5°C, and 40°C. Results: We observed major intraepicardial dispersion of AP duration (APD) and reversal of transmural gradient of APD in association with manifestation of BrS at 36.5°C. Reducing the temperature to 32°C prolonged APDs and enhanced the phase 1 notch of epicardial APs, while 40°C caused opposite changes. Prominent phase 2 domes of APs frequently led to spontaneous premature ventricular activations (PVAs), which conducted to surrounding regions having shorter APDs. Longer APDs at 32°C and 36.5°C frequently blocked reentry, although they promoted PVA, while shortened APDs at 40°C facilitated reentrant ventricular tachycardia. During bradycardia (2,000 ms), the J-ST elevation in the ECG was enhanced at 32°C and attenuated at 40°C. Rapid pacing (500 ms) eliminated the dome of epicardial APs and enhanced J-ST elevation at each temperature. Blocking the transient outward current, Ito, with 4-aminopyridine reduced J-ST elevation and eliminated the PVA and reentry. Conclusions: In this BrS model, prolongation and increased dispersion of APDs promoted spontaneous activation during hypothermia, while APD abbreviation facilitated reentry during hyperthermia. Ito mediated the arrhythmogenicity.

Original languageEnglish
Pages (from-to)188-197
Number of pages10
JournalHeart Rhythm
Issue number2
Publication statusPublished - Feb 2007
Externally publishedYes


  • Action potentials
  • Brugada syndrome
  • Electrophysiology
  • Mapping
  • Temperature modulation
  • Tissue
  • Ventricular arrhythmia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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