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3. Worth HM: Principles and Practice of Oral Radiographic Interpretation. Chicago: Yearbook Medical, 1963, pp 420-424 4. Moloney F, Worthington P: The origin of the Le Fort I maxillary osteotomy: Cheevers operation. J Oral Surg 39:731, 1981 5. Archer DJ, Young S, Uttley D: Basilar aneurysms: A new transclival approach via maxillotomy. J Neurosurg 67:54, 1987 6. Sndor GK, Charles DA, Lawson VG, et al: Oral approach to the nasopharynx and clivus using the Le Fort I osteotomy with midpalatal split (translation). Int J Oral Maxillofac Surg 19:352, 1990 7. Owens BM, Scuman NJ, Mincer HH, et al: Dental odontomas: A retrospective study of 104 cases. J Clin Pediatr Dent 21:261, 1997 8. Regezi JA, Kerr DA, Courtney R: Odontogenic tumors: Analysis of 706 cases. J Oral Surg 36:771, 1978 9. Toretti EF, Miller AS, Peezick B: Odontomas: An analysis of 167 cases. J Pedod 8:282, 1984 10. Kaugars GE, Miller ME, Abbey LM: Odontomas. Oral Surg Oral Med Oral Pathol 67:172, 1989
J Oral Maxillofac Surg 67:2021-2025, 2009

provides the superior access needed for removal of large lesions in the posterior maxilla. The Le Fort I down-fracture is a routine procedure in oral and maxillofacial surgery. Its postoperative morbidity is low, and the results are predictable, without changes to the occlusion after surgery. The Le Fort I down-fracture approach also gives an excellent view of the entire maxillary sinus, allowing well-visualized, safe, and thorough removal of the tumor.

References
1. Kramer IRH, Pindborg JJ, Shear M: WHO International Histological Classication of Tumors: Histological Typing of Odontogenic Tumors (ed 2). Berlin, Springer-Verlag, 1992, pp 21-22 2. Singer SR, Mupparapu M, Milles M, et al: Unusually large complex odontoma in maxillary sinus associated with unerupted tooth. N Y State Dent J 73:51, 2007

Brugada Syndrome (Sudden Unexpected Death Syndrome): Perioperative and Anesthetic Management in Oral and Maxillofacial Surgery
Nicholas Theodotou, BDS, DDS,* and Joseph E. Cillo, Jr, DMD, MPH
Brugada syndrome (BrS), rst described by Brugada and Buogada1 in 1992, is a rare genetic disease characterized by abnormal electrocardiogram (ECG) ndings and an increased risk of sudden cardiac death (SCD) by ventricular brillation. It is also known as sudden unexpected death syndrome. We report on the case of a patient with this disease and provide an overview of the perioperative and anesthetic treatment of the oral and maxillofacial surgery patient.

Report of a Case
A 55-year-old man presented to the oral and maxillofacial surgery clinic at Allegheny General Hospital (Pittsburgh, PA) with a chief complaint of pain and intraoral swelling of the right side of his mouth. The clinical and radiographic examinations revealed an odontogenic infection from numerous grossly carious and nonrestorable teeth. His medical history was signicant for myocardial infarction associated with occlusion of the right coronary artery 5 years before presentation, hypertension, stable angina, mitral valve prolapse without regurgitation, claudication pain, hypercholesteremia, hiatal hernia, and Brugada syndrome. His surgical history was signicant for 2 stents placed in the right coronary artery 5 years previously and an internal cardioverter-debrillator (ICD) placed 1 year before presentation. The oral medications routinely taken by the patient were metoprolol 12.5 mg twice daily, aspirin 81 mg daily, pantoprazole 75 mg daily, and atorvastatin 40 mg daily. His social history was positive for tobacco, alcohol, and marijuana abuse. His medical history included myocardial infarction in 2001 and numerous visits to the emergency department with complaints of chest pain and dyspnea dating back to 1999. In 2005, he presented to the emergency department complaining of mid-chest pain and pressure and associated dyspnea. He had experienced occasional palpitations and

Received from the Division of Oral and Maxillofacial Surgery, Allegheny General Hospital, Pittsburgh, PA. *Resident. Associate Program Director and Director of Research. Address correspondence and reprint requests to Dr Cillo: Division of Oral and Maxillofacial Surgery, Allegheny General Hospital, 320 East North Avenue, Suite 0107, Pittsburgh, PA 15212; e-mail: jecdna@aol.com
2009 American Association of Oral and Maxillofacial Surgeons

0278-2391/09/6709-0034$36.00/0 doi:10.1016/j.joms.2009.04.043

2022
episodes of lightheadedness and near-syncope during the previous 3 months, with more recent chest pain during the previous 2 weeks. The initial ECG ndings were within normal limits; however, after a few hours, a follow-up ECG showed 5 beats of ventricular tachycardia (VT) and was diagnosed as nonspecic VT. A more detailed family history revealed the presence of Brugada syndrome with SCD in 3 family members: a paternal rst cousin and 2 paternal second cousins. He was subsequently admitted to the hospital, during which time he experienced persistent near-syncopal episodes for the next 5 days. Transthoracic echocardiography revealed that the left and right ventricles were of normal size and function, with a left ventricular ejection fraction of 60%. All cardiac valves were normal, except for a mitral valve that was focally calcied with mildly thickened leaets and calcied aortic valve leaets. A nuclear perfusion test was performed using the Myoview stress test (technetium-99m tetrofosmin, GE Healthcare, Piscataway, NJ), a cardiac imaging agent useful in the diagnosis and localization of regions of reversible myocardial ischemia in the presence or absence of infarction in exercise and rest conditions. The results showed normal myocardial perfusion and normal left ventricular systolic function compared with a study done 4 years earlier. An adenosine stress test with myocardial perfusion imaging was performed, with ndings of sinus bradycardia within normal ECG ndings at baseline, with no ST-segment changes occurring during stress and recovery. The impression was that no ischemic ST-segment changes, no dysrhythmias other than rare premature ventricular contractions, and nonspecic chest discomfort associated with the adenosine infusion were present, similar to the ndings of a study performed 4 years earlier. Additionally, an electrophysiology study was performed that revealed polymorphic re-entry-type VT of less than 30 seconds in duration. The conclusions were that the abnormal sinoatrial node, atrioventricular node, and bundle of His conduction contributed to the inducible VT. Because of the previous symptoms of lightheadedness and presyncope, the positive family history for Brugada syndrome, and the results of the electrophysiology study, it was recommended by his cardiologist that an ICD be placed prophylactically to protect from VT and SCD. A Medtronic7278 ICD (Medtronic, Minneapolis, MN) generator implant was placed with the patient under general anesthesia; the initial rhythm was set at sinus bradycardia of 55 beats per minute. The denitive treatment plan for the patient was intraoral incision and drainage and extraction of the associated grossly carious teeth. Consultation with the patients cardiologist was initiated, and recommendations were received to turn off the patients ICD and have the procedure completed under general anesthesia in the operating room. Subsequently, before entry to the operating room, the patients ICD was turned off, and external debrillator pads were applied in the usual fashion and connected to a cardioverter/debrillator unit. The patient was given a rapidsequence intravenous general anesthesia induction of 50 mg lidocaine, 160 mg propofol, and 100 mg succinylcholine. No nondepolarizing neuromuscular blocking drug was administered during surgery. Sevourane anesthetic gas (1.0% end-tidal percentage) was used with an oxygen/nitrous oxide gas mixture (ratio of 1:1 L/min) for maintenance of general anesthesia; 15 mg lidocaine with 1:100,000 epinephrine was injected intraorally for local anesthesia at the surgery site. This resulted in a slight decrease in blood pressure that was successfully treated with 10 mg of ephedrine intravenously. No intraoperative complications or adverse cardiac situations developed. After completion of the

BRUGADA SYNDROME surgical procedure, the patient emerged uneventfully from anesthesia and was extubated and transferred to the postanesthesia care unit in stable condition. The ICD was turned on in the postanesthesia care unit, and the device functioned normally on reactivation. The patients heart rate was 58 beats per minute with nonspecic T-wave changes compared with his ECG from 9 months previously. The patient recovered uneventfully and was discharged the same day in stable condition following the standard hospital discharge criteria.

Discussion
Brugada and Buogada,1 in 1992, were the rst to identify a distinct clinical entity that caused SCD in patients by ventricular brillation. Their report presented data from 8 patients with recurrent episodes of aborted SCD. A syncopal episode without any prodrome was the rst manifestation of the disease. With 1 exception, all the patients had had normal ndings on physical examination, with no evidence of any cardiac or intracardiac disease. Other than the episode of ventricular arrhythmias, all patients had normal sinus rhythm. A sustained polymorphic ventricular tachycardia was documented to be the cause of the SCD in all 8 patients. The arrhythmia was not preceded by short-long sequences, and the initiating ventricular premature beat had a short coupling interval. Before the arrhythmia, no additional changes in repolarization were observed, suggesting ischemia or QT interval prolongation.1 BrS is generally characterized by a typical ECG pattern of right bundle branch block and persistent ST-segment elevation in leads V1 to V3 (Fig 1), with a structurally normal heart.2 Although the presence of a structurally normal heart in patients with BrS has been considered standard, recent evidence has challenged this notion. Frustaci et al3 have shown that despite an apparently normal heart during a noninvasive evaluation, histopathologic examination of endomyocardial biopsy specimens detected structural alterations, such as microaneurysms and myocyte cytoplasm degeneration, in all 18 patients with BrS in their study. They concluded that mutations in the SCN5A gene, which were identied in a portion of their patients, might have induced concealed structural abnormalities of myocardiocytes that accounted for paroxysmal arrhythmic manifestations. As an autosomal dominantly inherited arrhythmogenic disease, BrS is a cardiac channelopathy, with the underlying cause a dysfunction in the sodium ion channels of myocytes, and is caused, in part, by genetic defects in the -subunits of the cardiac sodium channel SCN5A located on the short arm of the third chromosome (3p21).4-7 Most SCN5A mutations lead to loss of function of the Nav1.5 channel by reducing the sodium current available during phase 0 (up-

THEODOTOU AND CILLO

2023 vidual study has compared the risks directly. BrS is the most common cause of sudden death in Southeast Asia in those younger than 50 years with no underlying cardiac disease.12 In BrS, ventricular brillation and SCD mainly occur in the resting state, predominantly during sleep.13,14 In patients with BrS, the ST-segment elevation was augmented during bradycardia to a similar extent in both symptomatic and asymptomatic patients. An inhibited prolongation of the QT interval during bradycardia was characteristic of symptomatic patients.15 Triggering mechanisms have been speculated to be bradycardia dependent. This could explain the greater incidence of SCD at night in those with the syndrome. It was brought about by autonomic nerve modulation, particularly vagal stimulation. This created ventricular tachyarrhythmias in BrS, as reported by several investigators.16-18 Additionally, it was found that characteristic changes diagnostic of BrS were augmented by a large meal. These data are associated with a history of life-threatening events in those with BrS.19 It has been suggested that a positive large meal test could be used for risk stratication between high- and low-risk patients.20 BrS could also be induced by Class Ia antiarrhythmic drugs such as ajmaline,21 epidural bupivacaine,22 ecainide, disopyramide, and procaineamide,23 which worsen the ST-segment elevation. Class IIa antiarrhythmic drugs such as mexiletine and lidocaine appear to have no effect on ST-segment elevation in these patients.24 BrS was relieved by low-dose isoproterenol.25 Fever has also been described as a trigger for BrS, because the sodium channel ionic mechanisms responsible for the ECG phenotype are temperature dependent.26 Additionally, the vagal stimulation associated with nausea and vomiting has also been shown to be a trigger for BrS.27 A meta-analysis study for risk stratication28 found that a history of syncope or SCD, the presence of spontaneous type I Brugada ECG ndings, and male gender predict a more malignant natural history. The results of that meta-analysis support the implantation of an ICD in symptomatic patients with type I Brugada ECG ndings. Data were insufcient to measure the overall risk of events in asymptomatic women with type I Brugada ECG ndings or asymptomatic patients with only drug-induced type I Brugada ECG ndings; however, it was suggested that these patients likely had a low risk of future events and could be closely followed up with no additional intervention. The only effective method of management for BrS is an ICD.7,29 According to the report, Brugada syndrome: Report of the Second Consensus Conference,30 patients with spontaneous drug-induced type I Brugada ECG ndings and a history of syncope or SCD should undergo ICD implantation. Asymptomatic patients with drug-induced type I Brugada ECG ndings or asymptomatic patients with drug-induced

FIGURE 1. Typical ECG of patient with BrS. Note, pattern resembling right bundle branch block, P-R prolongation, and ST elevation in leads V1 to V3. Reprinted, with permission, from Brugada, available from: http://www.brugada.org/about/disease-denition .html. Theodotou and Cillo. Brugada Syndrome. J Oral Maxillofac Surg 2009.

stroke) and phase 1 (early repolarization) of the cardiac action potential. Loss-of-function mutations in this gene lead to a loss of the action potential dome of some epicardial areas of the right ventricle, resulting in transmural and epicardial dispersion of repolarization. The transmural dispersion underlies ST-segment elevation and the development of a vulnerable window across the ventricular wall. In contrast, the epicardial dispersion of repolarization facilitates the development of phase 2 re-entry, which generates a phase 2 re-entrant extrasystole that captures the vulnerable window to precipitate ventricular tachycardia and/or brillation, which often results in SCD.8 The cases described have involved an autosomal dominant mode of transmission, and a family history of sudden death or malignant arrhythmia has often been present. Although the syndrome is inherited by both males and females, an 8:1 predilection for males has been reported.9-11 Although the incidence of BrS is not well established, it might cause 4 to 10 sudden deaths per 10,000 people annually in the United States. Data are suggestive that Asians (particularly those of Thai and Laotian descent and almost exclusively targeting males), compared with Europeans, might have a greater risk of events, although no indi-

2024 ECG ndings and a family history of SCD should undergo an electrophysiologic study to guide the selection for ICD implantation. Patients with this syndrome have a very poor prognosis when left untreated, because one third of the patients who experience syncopal episodes, or who are resuscitated from near-sudden death, develop additional episodes of polymorphic VT within 2 years.31 However, the prognosis of asymptomatic individuals with typical ECG ndings is also poor. Despite not having any previous symptoms, one third of these individuals will also present with a rst polymorphic VT or ventricular brillation within 2 years of followup. The cumulative proportion of ventricular brillation or cardiac arrest occurred in approximately 60% of the patients within 1 year, and 40% were likely to die suddenly if untreated. Furthermore, patients who have recurrent events but do not die face the risk of experiencing anoxic encephalopathy in mild to disabling forms. Because antiarrhythmic drugs (amiodarone or -blockers) do not protect against SCD, the only available treatment is the ICD. This device effectively recognizes and treats the ventricular arrhythmias. When provided with the ICD, the total mortality of patients with BrS has been 0% with up to 10 years of follow-up.31 In light of the 0% mortality rate during a 10-year period after placement of an ICD,31,32 with no preoperative cardiac abnormal ndings, the choice of anesthetic management for our patient was either a general anesthetic or in-ofce moderate intravenous sedation. The decision to treat the patient under general anesthesia was made in conjunction with input from the patients cardiologist. In-ofce intravenous sedation could have been used as well, because treatment of patients with ICDs is routinely performed in the dental ofce.
ANESTHETIC MANAGEMENT

BRUGADA SYNDROME

caused by double missense mutations of the cardiac sodium channel in a patient with BrS. They advocated caution in patients with BrS who might be a silent carrier of the double missense mutation of BrS. A review of the published data33-42 indicated a number of common principles and drugs that have been recommended for the perioperative treatment of patients with BrS: 1. Application of external biphasic debrillator connected to debrillator pads 2. Turning off the ICD immediately before surgery 3. Attaching a 12-lead ECG during the anesthesia 4. Continuous blood pressure monitoring 5. Atropine and ephedrine administration to decrease vagal tone 6. Isoprotenerol used to ameliorate ST-segment elevation 7. Avoidance of certain drugs, such as bupivacaine 8. Turning the ICD back on immediately at conclusion of surgery 9. Attention and management of postoperative fever, nausea, and vomiting Postoperative intensive care unit monitoring for 24 hours has been recommended,43 because relevant variations in the ST patterns in the V1 and V2 leads with 24-hour ECG monitoring have been detected in patients who received general anesthesia but were not associated with the incidence of arrhythmias.48 Because both temperature-dependent sodium channels and vagal stimulation27 have been shown to trigger BrS, postoperative fever and nausea and vomiting must be closely monitored and prevented. In our patient, the decision to turn off the ICD was made after consultation with the patients cardiologist. Given the nature of the patients condition and surgery, the use of electrocautery was a possibility; thus, to avoid the potential complications of electromagnetic interference, the emerging consensus appears to be that the ICDs antitachycardia functions should be inactivated during surgery if electrocautery is to be used during the procedure.49 However, if electrocautery is not anticipated, the ICD generally does not need to be turned off. Additionally, although it has been recommended that the patient undergo 24 hour postoperative intensive care unit monitoring, it is not mandatory. In our patient, consultation with the patients cardiologist allowed a stable same-day discharge. BrS is a potentially life-threatening, but manageable, cardiac condition that oral and maxillofacial surgeons may encounter in their patients. Using these established guidelines and recommendations and with close communication with the patients cardiologist, safe perioperative treatment of the patient with BrS is possible.

Most of the published data available for the anesthetic management of BrS has involved general anesthesia.33-42 The key aspects of anesthetic management are to administer the proper medications during the anesthesia of the patient with BrS. The administration of propofol, fentanyl, atracurium, air, and oxygen43 or propofol and midazolam, or propofol, sevourane, and fentanyl44 have been shown to be safe from triggering BrS. The avoidance of certain drugs commonly used in oral and maxillofacial surgery is advisable, such as bupivacaine, which Veernoy et al45 reported could induce the ECG and arrhythmic manifestations of BrS in silent carriers of SCN5A mutations. Additionally, although previous studies have shown that the administration of lidocaine suppresses BrS,46 Barajas-Martnez et al47 reported a rare lidocaine-induced BrS ECG pattern in a very rare case

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patients with Brugada syndrome. J Am Coll Cardiol 27:1061, 1996 Watanabe A, Fukushima Kusano K, Morita H, et al: Low-dose isoproterenol for repetitive ventricular arrhythmia in patients with Brugada syndrome. Eur Heart J 27:1579, 2006 Wakita R, Watanabe I, Okumura Y, et al: Brugada-like electrocardiographic pattern unmasked by fever. Jpn Heart J 45:163, 2004 Arai M, Nakazawa K, Takagi A, et al: Brugada syndrome-like ST-segment elevation increase exacerbated by vomiting. Circ J 68:712, 2004 Gehi AK, Duong TD, Metz LD, et al: Risk stratication of individuals with the Brugada electrocardiogram: A meta-analysis. J Cardiovasc Electrophysiol 17:577, 2006 Wang K, Yamauchi K, Li P, et al: Cost-effectiveness of implantable cardioverter-debrillators in Brugada syndrome treatment. J Med Syst 32:51, 2008 Antzelevitch C, Brugada P, Borggrefe M, et al: Brugada syndrome: Report of the second consensus conference. Heart Rhythm 2:429, 2005; Erratum in Heart Rhythm 2:905, 2005 Brugada J, Brugada R, Brugada P: Right bundle-branch block and ST-segment elevation in leads V1 through V3: A marker for sudden death in patients without demonstrable structural heart disease. Circulation 97:457, 1998 Duke J: Anesthesia Secrets (ed 3). Philadelphia, Mosby Elsevier, 2006, p 427 Hines R, Marschall K: Stoeltings Anesthesia and Co-Existing Disease (ed 5). Philadelphia, Churchill Livingstone, 2008, p 84 Antzelevitch C, Brugada R: Fever and Brugada syndrome. Pacing Clin Electrophysiol 25:1537, 2002 Antzelevitch C, Nof E. Brugada syndrome: Recent advances and controversies. Curr Cardiol Rep 10:376, 2008 Cordery R, Lambiase P, Lowe M, et al: Brugada syndrome and anesthetic management. J Cardiothoracic Vasc Anesth 20:407, 2006 Inamura M, Okamoto H, Kuroiwa M, et al: General anesthesia for patients with Brugada syndrome. A report of six cases. Can J Anesth 52:409, 2005 Santambrogio LG, Mencherini S, Fuardo M, et al: The surgical patient with Brugada syndrome: A four-case clinical experience. Anesth Analg 100:1263, 2005 Kim JS, Park SY, Min SK, et al: Anaesthesia in patients with Brugada syndrome. Acta Ansthesiol Scand 48:1058, 2004 Edge CJ, Blackman DJ, Gupta K, et al: General anaesthesia in a patient with Brugada syndrome. Br J Ansth 89:788, 2002 Priori SG, Napolitano C, Gasparini M, et al: Natural history of Brugada syndrome: Insights for risk stratication and management. Circulation 105:1342, 2002 Brugada P, Geelen P, Brugada R, et al: Prognostic value of electrophysiologic investigations in Brugada syndrome. J Cardiovasc Electrophysiol 12:1004, 2001 Vaccarella A, Vitale P, Presti CA: General anaesthesia in a patient affected by Brugada syndrome. Minerva Anestesiol 74: 149, 2008 Inamura M, Okamoto H, Kuroiwa M, et al: General anesthesia for patients with Brugada syndrome: A report of six cases. Can J Anesth 52:409, 2005 Vernooy K, Sicouri S, Dumaine R, et al: Genetic and biophysical basis for bupivacaine-induced ST segment elevation and VT/VF: Anesthesia unmasked Brugada syndrome. Heart Rhythm 3:1074, 2006 Itoh H, Tsuji K, Sakaguchi T, et al: A paradoxical effect of lidocaine for the N406S mutation of SCN5A associated with Brugada syndrome. Int J Cardiol 18:239, 2007 Barajas-Martnez HM, Hu D, Cordeiro JM, et al: Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel. Circ Res 103:396, 2008 Brunetti ND, De Gennaro L, Pellegrino PL, et al: Intra day ECG variation after general anesthesia in Brugada syndrome. J Interv Card Electrophysiol 21:219, 2008 Stone KR, McPherson CA: Assessment and management of patients with pacemakers and implantable cardioverter debrillators. Crit Care Med 32:S155, 2004 (suppl)

References
1. Brugada P, Buogada J: Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 20:1391, 1992 2. Hong K, Berruezo-Sanchez A, Poungvarin N, et al: Phenotypic characterization of a large European family with Brugada syndrome displaying a sudden unexpected death syndrome mutation in SCN5A. J Cardiovasc Electrophysiol 15:64, 2004 3. Frustaci A, Priori SG, Pieroni M, et al: Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation 112:3680, 2005 4. Chen Q, Kirsch GE, Zhang D, et al: Genetic basis and molecular mechanism for idiopathic ventricular brillation. Nature 392: 293, 1998 5. Antzelevitch C: The Brugada syndrome: Ionic basis and arrhythmia mechanisms. J Cardiovasc Electrophysiol 12:268, 2001 6. Eckardt L, Probst V, Smits JP, et al: Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation 111:257, 2005 7. Brugada P, Brugada R, Brugada J, et al: Use of the prophylactic implantable cardioverter debrillator for patients with normal hearts. Am J Cardiol 83:98D, 1999 8. Viswanathan PC, Balser JR: Inherited sodium channelopathies: A continuum of channel dysfunction. Trends Cardiovasc Med 14:28, 2004 9. Remme CA, Wever EF, Wilde AA, et al: Diagnosis and long-term follow-up of the Brugada syndrome in patients with idiopathic ventricular brillation. Eur Heart J 22:400, 2001 10. Wilde AA, Antzelevitch C, Borggrefe M, et al; Study Group on the Molecular Basis of Arrhythmias of the European Society of Cardiology: Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Circulation 106:2514, 2002 11. Priori SG, Napolitano C, Gasparini M, et al: Natural history of Brugada syndrome: Insights for risk stratication and management. Circulation 105:1342, 2002 12. Nademanee K, Veerakul G, Nimmannit S, et al: Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation 96:2595, 1997 13. Matsuo K, Kurita T, Inagaki M, et al: The circadian pattern of the development of ventricular brillation in patients with Brugada syndrome. Eur Heart J 20:465, 1999 14. Litovsky SH, Antzelevitch C: Differences in the electrophysiological response of canine ventricular subendocardium and subepicardium to acetylcholine and isoproterenol: A direct effect of acetylcholine in ventricular myocardium. Circ Res 67:615, 1990 15. Mizumaki K, Fujiki A, Nishida K, et al: Bradycardia-dependent ECG changes in Brugada syndrome. Circ J 70:896, 2006 16. Nakazawa K, Sakurai T, Takagi A, et al: Autonomic imbalance as a property of symptomatic Brugada syndrome. Circ J 67:511, 2003 17. Kasanuki H, Ohnishi S, Ohtuka M, et al: Idiopathic ventricular brillation induced with vagal activity in patients without obvious heart disease. Circulation 95:2277, 1997 18. Mizumaki K, Fujiki A, Tsuneda T, et al: Vagal activity modulates spontaneous augmentation of ST elevation in the daily life of patients with Brugada syndrome. J Cardiovasc Electrophysiol 15:667, 2004 19. Ikeda T, Abe A, Yusu S, et al: The full stomach test as a novel diagnostic technique for identifying patients at risk of Brugada syndrome. J Cardiovasc Electrophysiol 17:602, 2006 20. Ott P, Marcus F: The Brugada syndrome: Can we predict the risk? J Cardiovasc Electrophysiol 17:608, 2006 21. Corrado D, Nava A, Buja G, et al: Familial cardiomyopathy underlies syndrome of right bundle branch block, ST segment elevation and sudden death. J Am Coll Cardiol 27:443, 1996 22. Phillips N, Priestley M, Denniss AR, et al: Brugada-type electrocardiographic pattern induced by epidural bupivacaine. Anesth Analg 97:264, 2003 23. Candiotti KA, Mehta V: Perioperative approach to a patient with Brugada syndrome. J Clin Anesth 16:529, 2004 24. Miyazaki T, Mitamura H, Miyoshi S, et al: Autonomic and antiarrhythmic drug modulation of ST segment elevation in 25. 26. 27. 28. 29. 30. 31.

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