E Oppenheimer1, E Akavia, S Shavit, A D Korczyn. 1. Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
Abstract
STUDY OBJECTIVE: The aim was to investigate the arrhythmogenic properties of several sympathomimetic amines and their antagonism by adrenergic blocking drugs. DESIGN: Arrhythmia was induced by the investigated drugs, injected intravenously: adrenaline (ADR); noradrenaline (NA); phenylephrine (PE); isoprenaline (IP); terbutaline (Tb) and salbutamol (Sb). ADR and PE were also tested for their arrhythmogenic properties after the administration of the adrenergic antagonists propranolol, phentolamine, or both. The dose required to induce arrhythmia and the proportion of animals that developed arrhythmia at a given dose were recorded. SUBJECTS: 63 anaesthetised cats of either sex, weight 2.0-4.3 kg, were used. MEASUREMENTS AND RESULTS: The electrocardiogram was recorded continuously. The arrhythmogenic potency sequence (expressed as arrhythmogenic dose, AD50 in micrograms) was: ADR 16; NA 24; PE 75; IP 133; Tb 500; Sb greater than 1000. The arrhythmogenic efficacy (in %) was: ADR 97; NA 91; PE 90; IP 82; Tb 50; and Sb 0. Propranolol and phentolamine were both effective in reducing the arrhythmogenic effects of ADR and PE. However, their combined administration was most effective and abolished the arrhythmias. CONCLUSIONS: Arrhythmogenicity is a property of sympathomimetic amines with either alpha or beta adrenergic effects, but simultaneous activation of both types of receptors is required for maximal manifestations. Similarly, antagonism at both sites is necessary in order to abolish arrhythmias induced by sympathomimetic amines completely.
STUDY OBJECTIVE: The aim was to investigate the arrhythmogenic properties of several sympathomimetic amines and their antagonism by adrenergic blocking drugs. DESIGN:Arrhythmia was induced by the investigated drugs, injected intravenously: adrenaline (ADR); noradrenaline (NA); phenylephrine (PE); isoprenaline (IP); terbutaline (Tb) and salbutamol (Sb). ADR and PE were also tested for their arrhythmogenic properties after the administration of the adrenergic antagonists propranolol, phentolamine, or both. The dose required to induce arrhythmia and the proportion of animals that developed arrhythmia at a given dose were recorded. SUBJECTS: 63 anaesthetised cats of either sex, weight 2.0-4.3 kg, were used. MEASUREMENTS AND RESULTS: The electrocardiogram was recorded continuously. The arrhythmogenic potency sequence (expressed as arrhythmogenic dose, AD50 in micrograms) was: ADR 16; NA 24; PE 75; IP 133; Tb 500; Sb greater than 1000. The arrhythmogenic efficacy (in %) was: ADR 97; NA 91; PE 90; IP 82; Tb 50; and Sb 0. Propranolol and phentolamine were both effective in reducing the arrhythmogenic effects of ADR and PE. However, their combined administration was most effective and abolished the arrhythmias. CONCLUSIONS: Arrhythmogenicity is a property of sympathomimetic amines with either alpha or beta adrenergic effects, but simultaneous activation of both types of receptors is required for maximal manifestations. Similarly, antagonism at both sites is necessary in order to abolish arrhythmias induced by sympathomimetic amines completely.