AUTONOMIC AND ANTIARRHYTHMIC DRUG MODULATION OF ST SEGMENT ELEVATION IN PATIENTS WITH BRUGADA SYNDROME

Objectives. We examined the modulatory effects of autonomic nervous sy stem and antiarrhythmic drugs on the ST segment in patients with Bruga da syndrome to gain an insight into the mechanism of ST segment elevat ion. Background. Right bundle branch block, ST segment elevation and v entricular tachyarrhythmias define a distinct clinical and electrocard iographic (EGG) syndrome (Brugada syndrome). However, the mechanism of ST segment elevation and the causes of this syndrome are unknown, Met hods. The study included four patients in whom structural heart or cor onary artery disease was excluded by noninvasive and invasive tests. H igh take off ST segment elevation of either the coved or saddle-back t ype in precordial leads V-1, V-2 and V-3 was seen in all patients, Thr ee patients experienced recurrent episodes of syncope or aborted sudde n cardiac death, and the remaining patient had palpitation. Autonomic receptor stimulation and blockade and intravenous administration of an tiarrhythmic drugs were performed during sinus rhythm while the 12-lea d ECG was recorded, Metaiodobenzylguanidine (MIBG) scanning and Holter monitoring were also performed, Results. Beta adrenoceptor stimulatio n by intravenous isoproterenol consistently reduced (greater than or e qual to 0.1 mV) ST segment elevation at or 80 ms after the J point in all four patients. Selective alpha-adrenoceptor stimulation by intrave nous norepinephrine in the presence of propranolol or by intravenous m ethoxamine consistently augmented, whereas alpha-adrenoceptor blockade reduced, ST segment elevation in three patients. Intracoronary acetyl choline or intravenous edrophonium or neostigmine augmented ST segment elevation without inducing coronary spasm in three of four patients. Class IA antiarrhythmic drugs also consistently augmented (three patie nts), whereas class IB drugs had no effect on (two patients) ST segmen t elevation. No abnormality was found on MIBG imaging or heart rate va riability in three patients, suggesting that autonomic dysfunction is not a primary disease process. Class IA drugs had no effect on ST segm ent in three control patients, suggesting that the ST segment elevatio n seen in patients with Brugada syndrome in response to the drugs is n ot a nonspecific response. Conclusions. ST segment elevation in patien ts with Brugada syndrome was augmented by selective stimulation of alp ha adrenoceptors or muscarinic receptors or by class IA drugs but was mitigated by beta-adrenoceptor stimulation or alpha-adrenoceptor block ade. These responses might be explained by postulating the presence of an area of early repolarization or a local ''depolarized'' area in th e ventricle causing ST segment elevation in this syndrome. Because onl y a small number of patients were studied, these possibilities need fu rther evaluation.