Regional myocardial ajmaline concentration and antiarrhythmic activity for ischaemia- and reperfusion-induced arrhythmias in rats.

1. Antiarrhythmic actions of ajmaline against ischaemia (left coronary artery occlusion for 15 min) and subsequent reperfusion-induced arrhythmias were investigated in anaesthetized rats. 2. Ajmaline (2 mg kg-1, i.v.) was effective in suppressing ischaemia-induced arrhythmias whether given pre- or post-occlusion. 3. Ajmaline diminished the reperfusion-induced arrhythmias completely when given pre-occlusion but had little effect when given post-occlusion. 4. Reperfusion-induced increases in plasma enzyme activities of lactate dehydrogenase, glutamate-oxaloacetate transaminase and creatine phosphokinase were prevented more effectively when ajmaline was given pre-occlusion rather than post-occlusion. 5. Fifteen min post-occlusion, the ajmaline concentrations in the ischaemic ventricle were 18.42 +/- 1.66 and 1.18 +/- 0.15 micrograms g-1 for pre- and post-occlusion administration, respectively. However, ajmaline concentrations in whole blood and normal ventricle were not significantly different between pre- and post-occlusion administration. 6. We suggest that the beneficial effect of ajmaline against reperfusion-induced arrhythmias is related to the ischaemic myocardial concentration of ajmaline which is markedly affected by the time of drug administration (i.e. pre- and post-occlusion).