How to Induce Arrhythmias with Dobutamine

Abstract

In 1975, Tuttle and Mills published an article on a new catecholamine discovered in 1970: dobutamine. Tuttle, a pharmacologist, and Mills, a chemist, modified the structure of isoprenaline to obtain a new drug. Isoprenaline through its action on β adrenergic receptors increases the cardiac contractility with the cost of an increased heart rate and proarrhythmic effect associated with an increase in blood pressure. After removing the hydroxyl group from isoproterenol, the new compound had a positive chronotropic and inotropic effect. By substitution of the side chains, they obtained a compound with less chronotropic effect that reduced the arrhythmogenic properties of the product. Dobutamine has a direct ß1 and ß2 stimulation effect with a dose-related increase in heart rate, myocardial contractility, and blood pressure. Dobutamine increases regional myocardial blood flow but at a dose of 20 μg/kg/min induces coronary flow heterogeneity less than that induced by Dipyridamole or Adenosine. Since it has no action on dopamine receptors, to induce norepinephrine release, is less prone to induce hypertension than is dopamine. Dobutamine has also a mild ß2 agonist activity, making it useful as a vasodilator Dobutamine increases the automaticity of the sinoatrial node and decreases the refractory period of the atrium and atrio-ventricular node as well as the atrio-ventricular conduction time. It also decreases the refractory period of both ventricles, healthy or ischemic. It was also demonstrated in the study of Masoni et al. that dobutamine decreases the sinus cycle length, the SNRT, and corrected SNRT. At the atrial and nodal levels, it decreases the AH interval, Wenckebach cycle length, AV nodal functional and effective refractory periods. Dobutamine has no effect on the HV interval. Besides an increase in the heart rate, dobutamine induces ventricular premature contractions in 3–15% of patients. Ventricular tachycardia can be induced by dobutamine infusion in a small percentage of patients. Ischemic patients, those with heart failure and known arrhythmias, are at higher risk of proarrhythmia.