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

Antiarrhythmic actions of ajmaline against ischaemia (left coronary artery occlusion for 15 min) and subsequent reperfusion‐induced arrhythmias were investigated in anaesthetized rats. Ajmaline (2 mg kg⁻¹, i.v.) was effective in suppressing ischaemia‐induced arrhythmias whether given pre‐ or post‐occlusion. Ajmaline diminished the reperfusion‐induced arrhythmias completely when given pre‐occlusion but had little effect when given post‐occlusion. 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. Fifteen min post‐occlusion, the ajmaline concentrations in the ischaemic ventricle were 18.42 ± 1.66 and 1.18 ± 0.15 μg 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. 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). 1988 British Pharmacological Society