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Dilated cardiomyopathy is a global myocardial abnormality in which it is likely that there are relatively homogeneous electrical conditions. The pattern of arrhythmic complications, especially atrial ectopic beats, ventricular ectopic beats and the brief salvoes of polymorphic ventricular tachycardia which are characteristic of the condition, suggest that triggered automaticity is a more likely arrhythmia mechanism than reentry. Although treatment with 'conventional' antiarrhythmic agents has an important place, drugs which alter myocardial loading conditions (and thus, thereby, a possible mechanism of triggered automaticity) may be effective. Therapeutic strategies directed against the basic disease processes are in an early stage of clinical development but they hold great promise for the future.

The magnitude of tolerance to the anti-anginal efficacy of transdermal nitroglycerin and the efficacy and safety of short (4 h) and long (10 h) nitrate-free intervals for its prevention, were investigated in a randomized, double-blind, placebo-controlled crossover trial of 4 week-long treatment regimens: placebo, continuous therapy with a 50 mg patch (10 mg.24 h-1), and 4 h and 10 h nitrate-free periods. Only patients showing greater than 1 min increase in time to 1 mm ST depression after acute patch administration were eligible. Twelve men completed the study. One other anti-anginal medication (a beta-blocker in nine and calcium antagonist in two) was permitted in a constant dose throughout the study. Patients underwent exercise testing on days 1 and 7 of each treatment period, and 24 h ambulatory ECG monitoring on day 6. Compared to placebo, transdermal nitroglycerin on day 1 significantly improved time to 1 mm ST depression by 35%, and time to angina, exercise duration and maximal workload by 21%, 13% and 9% respectively. These improvements were totally lost after 7 days' continuous therapy, but completely maintained by a 10 h nitrate-free period (improvements of 35%, 25%, 16% and 11% respectively) but not by a 4 h nitrate-free period (non-significant improvements of 15%, 2%, 4% and 1% respectively). The differences between 10 and 4 h nitrate-free were significant for each end-point. Neither duration of ambulatory ischaemia, nor the proportion of patients experiencing greater than or equal to 5 min ischaemia during the scheduled nitrate-free interval differed between treatments.(ABSTRACT TRUNCATED AT 250 WORDS)