期刊
HEART RHYTHM
卷 1, 期 2, 页码 210-217出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.hrthm.2004.03.061
关键词
ECG; right ventricular (RV) wedge; terfenadine; flecainide; ajmaline; procainamide; 4-aminopyridine
资金
- NHLBI NIH HHS [R01 HL047678, HL47678] Funding Source: Medline
- NHLBI NIH HHS [HL47678] Funding Source: Medline
OBJECTIVE We hypothesized that a combination of I-Na and I-Ca blockade may be more effective in causing loss of the epicardial action potential (AP) dome and precipitating the Brugada syndrome (BS). The present study was designed to test this hypothesis in an in vitro model of BS. BACKGROUND The Brugada syndrome is characterized by an ST segment elevation in the right precordial ECG leads and a high risk of sudden death. The ECG sign of BS is often concealed, but can be unmasked with potent sodium channel blockers. Using canine right ventricular (RV) wedge preparations, we previously developed an experimental model of BS using flecainide to depress the AP dome in RV epicardium. METHODS Intracellular APs and a transmural ECG were simultaneously recorded from canine RV wedge preparations. RESULTS Terfenadine (5-10 muM)-induced block of I-Ca and I-Na caused heterogeneous loss of the epicardial AP dome, resulting in ST segment elevation, phase 2 reentry (12/16), and spontaneous polymorphic VT/VF (6/16). Flecainide (less than or equal to7.5 muM), ajmaline (less than or equal to20 muM), and procainamide (less than or equal to300 muM) failed to generate polymorphic VT in any preparation except when combined with a calcium channel blocker (verapamil, less than or equal to20 muM). Terfenadine-induced ST segment elevation was normalized and arrhythmias suppressed following It. block with 4-aminopyridine (0.5-2 mM). CONCLUSION Our data suggest that combined sodium and calcium channel block may be more effective than sodium channel block alone in unmasking the Brugada syndrome and that pharmacologic agents that inhibit I-to may be useful in preventing lethal arrhythmias in patients with the syndrome. (C) 2004 Heart Rhythm Society. All rights reserved.
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