Anti Beta-Adrenoceptors Autoantibodies and idiopathic arrhythmias: functional effect

Human antibodies against the second extracellular loop of \uf062-adrenoceptors (AA\uf062A) 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\uf062A 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\uf062A (ELISA method), were functionally tested for possible chronotropic effects on spontaneously beating rat myocardiocytes. Pharmacological (bisoprolol and atropine) effects on AA\uf062A 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\ub16.36 SD, beats/min), up to 63.2% of the maximal effect of isoproterenol (10-5M). Such response was antagonised by \uf0621-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\uf06dM) to exclude inhibitory effects mediated by muscarinic receptors stimulation, no change was found. In conclusion, 46.7% of the AA\uf062A purified from seropositive pts with IA were functionally active, inducing tachycardia of rat myocardiocytes. This suggests a possible arrhythmogenic role of AA\uf062A, either by inducing a catecholamine-like automaticity enhancement by \uf0621-adrenoceptor stimulation (8 cases, blocked by bisoprolol), or affecting other molecular targets (6 cases unaffected by bisoprolol)