Temperature modulation of ventricular arrhythmogenicity in a canine tissue model of Brugada syndrome.
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 degrees C, 36.5 degrees C, and 40 degrees 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 degrees C. Reducing the temperature to 32 degrees C prolonged APDs and enhanced the phase 1 notch of epicardial APs, while 40 degrees 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 degrees C and 36.5 degrees C frequently blocked reentry, although they promoted PVA, while shortened APDs at 40 degrees C facilitated reentrant ventricular tachycardia. During bradycardia (2,000 ms), the J-ST elevation in the ECG was enhanced at 32 degrees C and attenuated at 40 degrees C. Rapid pacing (500 ms) eliminated the dome of epicardial APs and enhanced J-ST elevation at each temperature. Blocking the transient outward current, I(to), 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. I(to) mediated the arrhythmogenicity.
Morita
Hiroshi
H
Krannert Institute of Cardiology, Indiana University School of Medicine, IN 46202, USA.
Zipes
Douglas P
DP
Morita
Shiho T
ST
Wu
Jiashin
J
D000200:Action Potentials; D000818:Animals; D001831:Body Temperature; D053840:Brugada Syndrome / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005334:Fever / Q000503:physiopathology*; D007036:Hypothermia, Induced; D008012:Lidocaine / Q000031:analogs & derivatives; D018754:Ventricular Dysfunction / Q000503:physiopathology*
D008012:Lidocaine; C042288:pilsicainide