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BACKGROUND: The efficacy of drugs used to treat inducible monomorphic sustained ventricular tachycardia (VT) has been assessed by investigating their ability to suppress inducibility, but the mechanism of the drug action remains to be determined. OBJECTIVES: To determine electrophysiological variables that predict inducibility, divided doses of class I antiarrhythmic drugs were given and their effects were analysed, particularly the ability of the final dose to suppress inducibility. METHODS: The excitable gap was estimated by the zone of entrainment, which was defined as the difference between the cycle length of VT and the longest paced cycle length that interrupted VT during entrainment of VT with rapid pacing at paced cycle lengths in decrements of 10 ms. The cycle length of VT, the block cycle length, and the zone of entrainment were measured in the drug free state and after intermediate and final doses of procainamide, disopyramide, cibenzoline, and mexiletine. RESULTS: Sustained monomorphic VT with a mean (SD) cycle length of 285 (43) ms was induced in 8 patients. It was entrained and interrupted at the block cycle length of 231 (31) ms. The width of the zone of entrainment was 54 (23) ms. In 8 studies VT was not inducible at final doses of procainamide in 4, cibenzoline in 1, and mexiletine in 3. In another 10 studies (procainamide in 4, disopyramide in 1, cibenzoline in 2, and mexiletine in 3), VT remained inducible at the intermediate dose and at the final dose. The cycle length of VT was prolonged to a similar degree in studies of effective and ineffective drugs, but the cycle length that blocked VT was longer at the intermediate dose of the effective drugs. Consequently, the width of the zone of entrainment was significantly narrowed at the intermediate dose of effective drugs and the width of the zone of entrainment was narrower than when ineffective drugs were given (22 (13) ms v 76 (18) or 75 (37) ms at the intermediate and final doses respectively (P < 0.02). CONCLUSION: Drugs that narrowed the zone of entrainment were associated with non-inducibility of VT after the final dose of the drug was given. The baseline variables did not predict the responses to class I antiarrhythmic drugs.