The Effects of Sodium Channel Inhibitors on Early Arrhythmias Associated with Acute Myocardial Ischaemia

Abstract

The initial discovery that a compound possesses antiarrhythmic activity is usually made in simple screening models involving the use of arrhythmogenic chemicals like aconitine, chloroform or ouabain. If promising results are obtained in these tests then the potential antiarrhythmic drug may be tested (usually in conscious dogs) for its ability to suppress ventricular ectopic activity ensuing 1–2 days after the production of myocardial ischaemia. Historically this sequence of events holds especially for the group of drugs variously described as ‘membrane stabilisers’, ‘sodium channel blockers’ or ‘class 1 agents’ (Vaughan Williams, 1970). Consequently, there is comparatively little literature describing the effects of sodium channel blocking agents on the early experimental ventricular arrhythmias and fibrillation which occur within minutes of the onset of myocardial ischaemia. The reasons for this are many but surely include the difficulties involved in producing a consistent quantitative model in which to assess the protective actions of putative antiarrhythmic drugs. For instance, our own experiences have shown that one-stage coronary artery ligation does not produce ventricular ectopic activity in every species — rabbits and guineapigs being particularly resistant. In addition even in those species which demonstrate early ventricular arrhythmias (for example, the dog), ligation of the same coronary artery can be associated with a range of incidence of ventricular fibrillation (VF) of between zero and 100 per cent depending on the laboratory (see Stephenson et al., 1960, for review of early literature, and chapter 6 of this book).