Haemodynamic and electrophysiologic actions of alinidine in the dog

Abstract

Alinidine (St 567, 2-[N-allyl-N-(2,6-dichlorophenyl)-amino]-2-imidazoline), the N-allyl derivative of clonidine which causes a specific bradycardia at the sinus node, has been investigated for cardiovascular effects. In a total of 7 mongrel dogs anaesthetized with piritramide and respirated with nitrous oxide 1.5 mg/kg alinidine was injected intravenously and 2 hr later, long before subsidence of the effects, a further dose of 3 mg/kg was given. Heart rate was reduced by both doses (-38, -50% of control) while arterial blood pressure decreased slightly only with 3 mg/kg (-13%). Cardiac output (thermodilution) was diminished (-33, -54%) and total peripheral resistance increased (+48, +101%). Simultaneously contractility (dp/dtmax.; -27, -46%), cardiac volume work (-34, -60%), tension time index (-23, -38%) and coronary sinus blood flow (electromagnetic flowmeter) decreased (-22, -48%). These results suggest a reduction in myocardial oxygen demand as is confirmed by the detection of reduced myocardial oxygen consumption (-14, -44%). Oxygen content of the coronary venous blood remained unchanged. In contrast to cardiac output and femoral artery flow (-37, -37%) renal blood flow was not affected. In another group of 9 dogs anaesthetized with pentobarbitone His bundle EG and ECG were reported. Alinidine (1.5 mg/kg i.v.) prolonged the A-H interval under spontaneous contraction (+65%) as well as at atrial pacing with 120 stimuli/min (+64%), thus pointing to a retarded AV conduction. Two hr after the drug administration bradycardia and A-H prolongation were still fully developed. The intervals P-A, H-V and the QRS complex were not influenced. In 4 further dogs atrial pacing rate was increased in stages up to 300 stimuli/min and the maximal ventricular follow frequency determined. Alinidine (1.5 mg/kg i.v.) reduced the maximal follow frequency from 215 to 125 beats/min (-43%). This effect is considered as a consequence of the retarded conduction in the AV node.