Pharmacokinetics and antiarrhythmic activity of ajmaline in rats subjected to coronary artery occlusion

Abstract

1 The pharmacokinetics and the antiarrhythmic action of intravenous ajmaline were investigated in anaesthetized rats subjected to coronary artery occlusion. 2 Ajmaline (0.125-2mg kg', i.v. given just after occlusion) suppressed arrhythmias in a dosedependent manner, judged by the reduction of premature ventricular complexes. The incidence of malignant arrhythmias (ventricular tachycardia and fibrillation) was preferentially suppressed at the higher doses of ajmaline (I and 2 mg kg-'). 3 Coronary occlusion induced a change in pharmacokinetics of ajmaline (2 mg kg-) and its total body blood clearance was significantly decreased from 56.6 ml min -'kg-' in sham-operated rats to 43.1 ml min-'kg-' in rats after coronary occlusion. 4 Ajmaline exhibited a significantly increased negative dromotropic action (increased PQ interval) in rats after coronary occlusion compared with that in sham-operated rats. The difference seems to be due to the pharmacokinetic change since the concentration-effect relationship was similar in the two groups of rats. 5 We suggest that the measurement of drug levels is important in the assessment of antiarrhythmic agents.

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

“…Hence the AV conduction system might also be a possible site of drug action in rats subjected to coronary artery occlusion; and drugs which slow AV conduction might exert an antiarrhythmic effect. In this respect we have already shown that ajmaline slows AV conduction and that left coronary artery occlusion does not affect the negative dromotropic activity of ajmaline (Hashimoto et al, 1986).…”

“…It is known that in anaesthetized rats, ischaemic arrhythmias start 5 min after coronary artery occlusion and last for about 10min (Hashimoto et al, 1986). On the other hand, the incidence of reperfusion-induced arrhythmias is dependent on the duration of the preceding occlusion.…”

“…In a previous study, we have shown that ajmaline given post-occlusion protects against ischaemiainduced arrhythmias in a dose-related manner (Hashimoto et al, 1986). The present study was designed to compare the effect of ajmaline on ischaemia-and reperfusion-induced arrhythmias in rats.…”

Pharmacokinetics and dromotropic activity of ajmaline in rats with hyperthyroidism

“…We have shown that the negative dromotropic action of ajmaline for the AV conduction system can be quantitatively assessed by measuring the PQ interval in rats (Hashimoto et al, 1986) and dogs (Yasuhara et al, 1987). On the other hand, changes in the extent of the plasma protein binding have been shown to affect the responses of some antiarrhythmic drugs, including lignocaine (Rick et al, 1987) and disopyramide (Huang & 0ie, 1982).…”

“…As a model drug, we selected a Class I antiarrhythmic drug ajmaline, the dromotropic action of which on atrioventricular conduction can be assessed by measuring PQ intervals on the electrocardiogram in rats (Hashimoto et al, 1986). Because the pharmacological effects of ajmaline have been shown to be affected by plasma protein binding (Yasuhara et al, 1987), the dromotropic activity in hyperthyroid rats was determined from the plasma unbound concentration.…”