Anti Beta-Adrenoceptors Autoantibodies and idiopathic arrhythmias: functional effect

Human antibodies against the second extracellular loop of -adrenoceptors (AAA) might increase the beating rate of isolated neonatal rat myocardiocytes. In a previous study, 56.7% of patients (pts) with "idiopathic" arrhythmias (IA) were positive for those antibodies. Aim of this study was to evaluate the functional (chronotropic) effect of AAA of pts with IA on rat myocardiocytes. Methods: The sera of 30 pts, 16 with Lown 2-4 ventricular arrhythmias (VA) and 14 with supraventricular arrhythmias (SVA), idiopathic or due to cardiomyopathy, all positive for AAA (ELISA method), were functionally tested for possible chronotropic effects on spontaneously beating rat myocardiocytes. Pharmacological (bisoprolol and atropine) effects on AAA functional activity were also evaluated. Results: The sera of 14/30 (46.7%) arrhythmic pts, 7 with SVA (5 paroxysmal atrial fibrillation, 1 atrial flutter and 1 focal atrial tachycardia) and 7 with VA (6 Lown4 and 1 Lown2) induced a positive chronotropic effect of rat myocardiocytes (mean heart rate increase: 27.77±6.36 SD, beats/min), up to 63.2% of the maximal effect of isoproterenol (10-5M). Such response was antagonised by 1-selective blocker bisoprolol (10-6M) in 8/14 pts (2 VA and 4 SVA). In 6/16 pts sera without chronotropic effect (3 of VA and 3 of SVA pts) tested in the presence of atropine (1M) to exclude inhibitory effects mediated by muscarinic receptors stimulation, no change was found. In conclusion, 46.7% of the AAA purified from seropositive pts with IA were functionally active, inducing tachycardia of rat myocardiocytes. This suggests a possible arrhythmogenic role of AAA, either by inducing a catecholamine-like automaticity enhancement by 1-adrenoceptor stimulation (8 cases, blocked by bisoprolol), or affecting other molecular targets (6 cases unaffected by bisoprolol).