The arrhythmogenic action of sympathomimetic amines

Abstract

Intravenous infusions of different sympathomimetic amines were given to cats under chloraloseurethane anaesthesia. It was found that the action of catecholamines (adrenaline, noradrenaline, isoproterenol) in producing arrhythmia appeared in two distinctly separate forms: 1. A mainly primary (in some cases early and transitory) increase in susceptibility to external stimuli, as indicated by the considerable fall of the electrical fibrillation threshold. 2. A secondary (in some cases late) ventricular arrhythmia. The two forms differ in their underlying mechanism and in their response to therapeutic measures. The first form is mainly due to a stimulation of the adrenergic beta receptors as shown by the fact that the lowering of the fibrillation threshold could be produced only by catecholamines which stimulate beta receptors such as isoproterenol, adrenaline and noradrenaline. The two latter drugs also stimulate the alpha receptors and they produced a biphasic action, i.e., an early transient decrease followed by a lasting increase in the fibrillation threshold. The primary decrease in the fibrillation threshold could be prevented by specific blockade of the adrenergic beta receptors with 1-INPEA, medium doses of MJ 1999 or small doses of propranolol, thus practically excluding the possibility of a nonspecific, ‘quinidine-like’ anti-arrhythmic action. The alpha receptor blocking agents phenoxybenzamine and hydergine were without effect. The secondary arrhythmia is mainly due to over-loading of the heart caused by increased blood pressure, as it appeared only after catecholamines possessing hypertensive effect and could be prevented by inhibiting the rise in blood pressure, e.g., by blockade of the adrenergic alpha receptors. Specific blockade of the beta receptors did not diminish, but sometimes increased the incidence of secondary arrhythmias, as it enhanced the rise in blood pressure caused by the catecholamines. Phenylephrine, methoxamine and synephrine, which act chiefly on the adrenergic alpha receptors, elevated auricular and ventricular fibrillation thresholds, thus showing primarily an anti-arrhythmic tendency. However, after repeated administration of phenylephrine (large doses of single intravenous injections to the anaesthetized dog) arrhythmias of a secondary type could also be seen.