title: Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome.
abstract: OBJECTIVE
  We examined the modulatory effects of autonomic nervous system and antiarrhythmic drugs on the ST segment in patients with Brugada syndrome to gain an insight into the mechanism of ST segment elevation.
  
  
  BACKGROUND
  Right bundle branch block, ST segment elevation and ventricular tachyarrhythmias define a distinct clinical and electrocardiographic (ECG) syndrome (Brugada syndrome). However, the mechanism of ST segment elevation and the causes of this syndrome are unknown.
  
  
  METHODS
  The study included four patients in whom structural heart or coronary artery disease was excluded by noninvasive and invasive tests. High take-off ST segment elevation of either the coved or saddle-back type in precordial leads V1, V2 and V3 was seen in all patients. Three patients experienced recurrent episodes of syncope or aborted sudden cardiac death, and the remaining patient had palpitation. Autonomic receptor stimulation and blockade and intravenous administration of antiarrhythmic drugs were performed during sinus rhythm while the 12-lead ECG was recorded. Metaiodobenzylguanidine (MIBG) scanning and Holter monitoring were also performed.
  
  
  RESULTS
  Beta-adrenoceptor stimulation by intravenous isoproterenol consistently reduced (> or = 0.1 mV) ST segment elevation at or 80 ms after the J point in all four patients. Selective alpha-adrenoceptor stimulation by intravenous norepinephrine in the presence of propranolol or by intravenous methoxamine consistently augmented, whereas alpha-adrenoceptor blockade reduced, ST segment elevation in three patients. Intracoronary acetylcholine 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 patients), whereas class IB drugs had no effect on (two patients) ST segment elevation. No abnormality was found on MIBG imaging or heart rate variability in three patients, suggesting that autonomic dysfunction is not a primary disease process. Class IA drugs had no effect on ST segment in three control patients, suggesting that the ST segment elevation seen in patients with Brugada syndrome in response to the drugs is not a nonspecific response.
  
  
  CONCLUSIONS
  ST segment elevation in patients with Brugada syndrome was augmented by selective stimulation of alpha-adrenoceptors or muscarinic receptors or by class IA drugs but was mitigated by beta-adrenoceptor stimulation or alpha-adrenoceptor blockade. These responses might be explained by postulating the presence of an area of early repolarization or a local "depolarized" area in the ventricle causing ST segment elevation in this syndrome. Because only a small number of patients were studied, these possibilities need further evaluation.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miyazaki
authors.forename: H
authors.initials: H
authors.lastname: Mitamura
authors.forename: S
authors.initials: S
authors.lastname: Miyoshi
authors.forename: K
authors.initials: K
authors.lastname: Soejima
authors.forename: Y
authors.initials: Y
authors.lastname: Aizawa
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004206:Disopyramide / Q000627:therapeutic use; D004562:Electrocardiography; D006801:Humans; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D008801:Mexiletine / Q000627:therapeutic use; D008875:Middle Aged; D011342:Procainamide / Q000627:therapeutic use; D013577:Syndrome; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000503:physiopathology*; D014700:Verapamil / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D008801:Mexiletine; D008012:Lidocaine; D014700:Verapamil; D004206:Disopyramide; D011342:Procainamide