Objective      To investigate the effect of mexiletine combined with ibutilide on electrophysiological characteristics of myocardia.       Methods      Arterially perfused canine left ventricular wedge preparations were isolated from mongrel dogs and perfused with normal Tyrodes’ solution

ibutilide Tyrodes’ solution

and mexiletine-ibutilide Tyrodes’ solution sequentially. Action potential duration (APD) of epicardium

mid-myocardium

and endomyocardium was measured under basic cycle length (BCL) of 500

667

1 000

2 000

and 4 000 ms repeatedly after the perfusate was changed.       Results      Ibutilide prolonged APD of all layers of myocardium (class Ⅲ effect) in a manner of reverse rate dependency (RRD)

with the most prominent effect on mid-myocardium (10.8±2.1 

vs 

20.4±3.0 

vs 

17.3±3.1 ms; 15.8±4.0 

vs 

31.0±5.7 

vs 

21.5±3.4; 18.4±3.5 

vs 

42.3±5.4 

vs 

24.0±3.5 ms; 23.0±3.6 

vs 

53.8±5.4 

vs 

31.3±3.6 ms; 25.6±4.2 

vs 

55.9±4.4 

vs 

34.8±3.2 ms

P0.01). Ibutilide also prolonged transmural dispersion of repolarization (TDR) in a manner of RRD. Mexiletine suppressed class Ⅲ effect of ibutilide and its RRD on all layers of myocardium

especially on mid-myocardium and reduced TDR.       Conclusion      Mexiletine combined with ibutilide can suppress class Ⅲ effect of ibutilide and its RRD

and enhance the safety of ibutilide.