当前位置： SCI文献检索 > CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY期刊下所有文献 > Effects of amiodarone and L8040, novel antianginal and antiarrhythmic drugs, on cardiac and coronary haemodynamics and on cardiac intracellular potentials.

Effects of amiodarone and L8040, novel antianginal and antiarrhythmic drugs, on cardiac and coronary haemodynamics and on cardiac intracellular potentials.

Abstract：

:1. The effects on the coronary and systemic haemodynamics of intravenous and intracoronary injections of two benzfuran derivatives, amiodarone and its brominated analogue (L8040), were studied in open-chest anaesthetized dogs. The effects of L8040 on cardiac intracellular potentials after 6 weeks of 20 mg/kg intraperitoneal injections in rabbits were also investigated. 2. Both compounds produced dose-related and quantitatively similar decreases in coronary vascular resistance following their intracoronary administration; threshold effects occurred with about 0-25 mg of each drug and maximal effects with 4 mg. Larger intracoronary doses produced measurable systemic effects. 3. Intravenous injections of amiodarone and L8040 (2-5-10 mg/kg) produced dose-related decreases in heart rate and aortic pressure with a fall in total peripheral resistance. The left ventricular output was either unaffected or increased with a consistent augmentation in stroke volume. 4. The bradycardia produced by both drugs was associated with prolongation of the P-R interval of the electrocardiogram with no significant effect on the QRS duration or the Q-T interval. 5. Each drug produced a decrease in the total peripheral vascular resistance with no change in left ventricular end diastolic pressure except after 10 mg/kg doses which led to an increase in this parameter. 6. Cardiac contractile force and peak LV dp/dt were reduced by both drugs in a dose-related manner. 7. Chronic intraperitoneal administration of L8040 in rabbits caused a prolongation of the duration of the atrial and ventricular intracellular potential without an effect on the maximal rate of depolarization. 8. The effect of amiodarone or L8040 on the coronary circulation and arterial pressure may be attributed to their vasodilator properties but their depressant actions on cardiac contractile force and peak LV dp/dt with an increase in left ventricular end diastolic pressure at high doses, also suggest intrinsic negative inotropic propensity for both compounds. 9. It is concluded that the overall effects on coronary and systemic haemodynamics of amiodarone and its brominated analogue are likely to permit a favourable influence on the balance of oxygen supply and demand in myocardial ischaemia; in addition, their actions on sino-atrial and atrio-ventricular conduction as well as those on cardiac repolarization suggest potential antiarrhythmic properties which merit investigation.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Singh BN,Jewitt DE,Downey JM,Kirk ES,Sonnenblick EH

doi

10.1111/j.1440-1681.1976.tb00620.x

subject

Has Abstract

pub_date

1976-09-01 00:00:00

pages

427-42

issue

eissn

0305-1870

issn

1440-1681

journal_volume

pub_type

杂志文章

在线工具

Effects of amiodarone and L8040, novel antianginal and antiarrhythmic drugs, on cardiac and coronary haemodynamics and on cardiac intracellular potentials.