Comparative effects of lignocaine and lorcainide on conduction in the Langendorff-perfused guinea-pig heart.

The effects of lignocaine and lorcainide on conduction through the AV node and the ventricular conduction system have been investigated in the Langendorff-perfused guinea-pig heart. Basal conduction times were estimated at 80 and 120/min; at each frequency extra-stimuli with variable coupling intervals were applied in order to determine the change in conduction velocity and estimate refractory periods. In most of the preparations paced at 80/min premature impulses were blocked at a site distal to the AV node (distal gate). In therapeutic concentrations (1 to 5 mg . litre-1) and at low frequency of stimulation lignocaine did not change basal conduction times but had a definite slowing effect on the conduction of extra-systoles. Slowing of basal conduction times became prominent at higher frequencies of stimulation or at concentrations above 5 mg . litre-1. In all conditions the effect on the ventricular conduction system was more pronounced than on the AV node. Compared with lignocaine, lorcainide was more effective and more selective. Important changes in basal conduction times and in conduction of premature impulses were observed at 0.31 and 0.63 mg . litre-1. The effect on conduction in the ventricular conduction system was more pronounced than on conduction in the AV node. The dose-effect relationship for different parameters was steeper with lorcainide than with lignocaine. At high concentrations of lorcainide (greater than 1.25 mg . litre-1) intermittent block, especially in the ventricular conduction system, was frequently observed.