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Monophasic action potential recordings during T-wave alternans in congenital long QT syndrome
Volume 132, Number 3 American Heart Journal
Shimizu et al.
699
pl/==l
800
400 200
0 llA,.~,Li]~
INFLATION
DIII~%ATION
Figure 1. Atrial natriuretic peptide plasma concentrations in coronary sinus (black bars) and in peripheral v e i n (hatched bars) before, during, a n d a f t e r P T C A - i n d u c e d m y o c a r d i a l ischemia, p < 0.02.
possibly b e c a u s e of t h e s m a l l n u m b e r . I n t h e only p a t i e n t w i t h a n i n s i g n i f i c a n t i n c r e a s e (5%) in c o r o n a r y s i n u s A N F c o n c e n t r a t i o n d u r i n g i s c h e m i a left v e n t r i c u l a r end-diastolic p r e s s u r e did not change. A direct effect of e n d o t h e l i n on a t r i a l myocites h a s b e e n s u g g e s t e d as a n o t h e r m e c h a n i s m for A N P release; a n i n c r e a s e of e n d o t h e l i n level in a r t e r i a l blood h a s b e e n found i m m e d i a t e l y a f t e r PTCA. 5 O u r d a t a s h o w t h a t a f t e r r e p e r f u s i o n t h e fall in c o r o n a r y sinus A N F c o n c e n t r a t i o n occurs v e r y r a p i d l y a l t h o u g h t h e r e is no a p p r e c i a b l e v a r i a t i o n in p e r i p h e r a l v e i n A N P concentration. C h e n u et ah, 3 who m e a s u r e d A N P concent r a t i o n in a r t e r i a l blood, found a p e r s i s t e n c e of i n c r e a s e d A N P c o n c e n t r a t i o n 20 m i n u t e s a f t e r t h e l a s t balloon inflation. The d e c r e a s e in A N P c o n c e n t r a t i o n in a r t e r i a l a n d v e n o u s blood a p p e a r s to occur g r a d u a l l y a f t e r r e p e r f u s i o n in c o n t r a s t to t h e r a p i d fall in t h e c o r o n a r y s i n u s blood. I n fact, it h a s b e e n s h o w n t h a t t h e A N P c o n c e n t r a t i o n in a p e r i p h e r a l vein, i n c r e a s e d w i t h i n t r a v e n o u s infusion of A N P , r e t u r n s to b a s a l v a l u e s 25 m i n u t e s a f t e r t h e e n d of t h e infusion, s T h e c o r o n a r y s i n u s A N P c o n c e n t r a t i o n no doubt b e t t e r reflects t h e A N P r e l e a s e f r o m t h e myocites; a c h a n g e in A N P p r o d u c t i o n should be i m m e d i a t e l y followed by a r e s p e c t i v e c h a n g e in its c o r o n a r y sinus concentration, M o r e o v e r it m u s t be u n d e r s c o r e d t h a t A N P is found in t h e c o r o n a r y s i n u s blood in m u c h h i g h e r c o n c e n t r a t i o n s t h a n a f t e r dilution in t h e p e r i p h e r a l blood, as w a s also d e m o n s t r a t e d in our p a t i e n t s . T h e t r a n s i e n t m y o c a r d i a l i s c h e m i a i n d u c e d by P T C A is a powerful s t i m u l u s to A N P release, m a i n l y t h r o u g h t h e m e c h a n i s m of myocites s t r e t c h i n g because of i n c r e a s e d left a t r i a l p r e s s u r e c o n s e q u e n t to i s c h e m i c left v e n t r i c u l a r dysfunction. As soon as r e p e r f u sion is r e - e s t a b l i s h e d w i t h balloon deflation, A N F r e l e a s e r e t u r n s to b a s e l i n e level s i m u l t a n e o u s l y w i t h t h e functional r e c o v e r y of t h e left ventricle. REFERENCES
1. Ikaheimo MJ, Ruskoaho HJ, Airaksinen EJ, Huikuri HV, Korhonen UR, Leppaluoto PJ, et al. Plasma levels of atrial natriuretic peptide during myocardial ischemia induced by percutaneous translumina]
2. 3. 4. 5. 6.
7. 8.
coronary angioplasty or dynamic exercise. Am Heart J 1989;117:83741. Prachar H, Ogris E, Dittel M, Enenkel W. Rapid changes of atrial natriuretic peptide concentration during percutaneous transluminal coronary angioplasty. AMHEARTJ 1991;122:157-63. Chenu PC, Donckier JE, Schroeder E, Berbinski A, Ketelslegers JM, Marchandise B, et al. Atrial natriuretic factor during percutaneous transluminal coronary angioplasty. Acta Cardiol 1991;XLVI:595-603. Malatino LS, Leonardi C, Stancanelli B, Polizzi G, Grassi R, Tamburino C, et al. Transient myocardial ischemia stimulates atrial natriuretic factor release. Am Heart J 1992;123:693-8. Ameli S, Kaul S, Castro L, Arora C, Mirea A, Shah PK. Effect of percutaneous transluminal coronary angioplasty on circulating endothelin levels. Am J Cardiol 1993;72:1352-6. Sugawara A, Nakao K, Morii N, Sakamoto M, Suda M, Shimokura M, et al. Alpha-human atrial natriuretic peptide is released from the heart and circulates in the body. Biochem Biophys Res Commun 1985; 129:439-46. Anderson JV, Donckier J, McKenna WJ, BloomSR. The plasma release of atrial natriuretic peptide in man. Clin Sci 1986;71:151-5. Anderson JV, Donckier J, Payee NN, Beacham J, Slater JDH, Bloom SR. Atrial natriuretic peptide: evidence of action as a natriuretic hormone at physiological plasma concentrations in man. Clin Sci 1987;72:305-12.
Monophasic action potential recordings during T-wave alternans in congenital long QT syndrome W a t a r u S h i m i z u , MD, K a t s u h i k o Y a m a d a , MD, Yoshio A r a k a k i , MD, T e t s u r o K a m i y a , MD, a n d K a t s u r o S h i m o m u r a , M D Osaka, Japan From the Division of Cardiology, Department of Internal Medicine, and Department of Pediatrics, National Cardiovascular Center. Dr. Shimizu is supported in part by a grant from Japan Cardiovascular Research Foundation by Bayer Cardiovascular Disease Research Scholarship. Reprint requests: Wataru Shimizu, MD, Divisin of Cardiology,Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, Japan 565. Am Heart J 1996;132:699-701. Copyright © 1996 by Mosby-Year Book~Inc. 0002-8703/96/$5.00 + 0 4/4/~1988
700
September 1996 American Heart Journal
Shimizu et at.
III
,.F,~11my '
I
1 sec
Fig. 1. Six-lead electrocardiograms showing T-wave alternans during electrophysiologic study. Alternating changes in morphologic characteristics and polarity of the T wave were prominent in leads II, III, V1, and V5.
T-wave alternans is a rare but characteristic electrocardiographic (ECG) finding defined as alternating changes in the morphologic characteristics and polarity ofT waves in patients with congenital long QT syndrome (LQTS)fl 2 Twave alternans is thought to be related to spatial and temporal heterogeneity of repolarization from changes in action potential duration. 3 Monophasic action potential (MAP) has recently been used to detect membrane phenomena in beating hearts, and prolonged MAP duration and early afterdepolarization (EAD)-like activity have been demonstrated in congenital LQTS patients. 4 We recently recorded MAP during T-wave alternans in a patient with this syndrome. The patient was a 3-year-old boy with congenital LQTS who had QT prolongation (corrected QT interval [QTc] = 740 msecl/2). He had some episodes of stressinduced syncope and torsades de pointes, and spontaneous T-wave alternans was sometimes documented. His mother also had corrected QT interval prolongation. Electrophysiologic study was performed while the patient was sedated
with sodium pentobarbital (3 mg/kg) and diazepam (0.3 mg/kg) without antiarrhythmic drugs. MAP was recorded to examine the effects of intravenous antiarrhythmic drugs (e.g., verapamil or propranolol) directly on the action potential. All protocols were reviewed and approved by our Ethical Review Committee, and written informed consent was obtained from his parents. Two 6F MAP catheters (MAP pacing combination catheter, EP Technologies Inc., Sunnyvale, Calif.) were introduced through a femoral vein and advanced into the right ventricle, and one 6F MAP catheter was also introduced through a femoral artery and advanced into the left ventricle with fluoroscopic guidance. MAPs were simultaneously recorded from the left ventricular (LV) lateral wall (LVlat MAP), the right ventricular (RV) outflow tract (RVOT MAP), and the RV septum (RVsep MAP) with six surface ECG leads during sinus rhythm. Spontaneous T-wave alternans occurred during simultaneous MAP and ECG recordings. Six-lead ECG recording at a paper speed of 25 mm/sec showed typical T-wave alternans marked in leads II, III, V1 and V5 (Fig. 1). Fig. 2 shows simultaneous recordings from ECG leads V1 and V5 and MAPs from the same three sites at a paper speed of 100 mm/sec. The morphologic characteristics and duration of the QRS in the ECG recording and the activation time (AT) (the time between QRS onset and steep MAP upstroke) did not change from beat to beat. However, electrical alternans of the repolarization time (RT) (AT + MAP duration at 90% repolarization) were recorded at all MAP recording sites (LVlat MAP, 425 to 400 msec; RVOT MAP, 435 to 445 msec; RVsep MAP, 400 to 440 msec) associated with T-wave alternans in the ECG leads V1 and Vs: Moreover, temporally electrical alternans between the LVlat MAP and the RVsep MAP were demonstrated. That is, the RT of the first and third beats in Fig. 2 was longer in the LVlat MAP (425 msec) than in the RVsep MAP (400 msec), whereas the second and fourth beats had shorter RT in the LVlat MAP (400 msec) than in the RVsep MAP (440 msec). Although EAD-like activities were constantly recorded in the RVsep MAP, these activities were not directly related to the T-wave alternans in this patient. Several experimental studies suggested that electrical alternans depends on intracellular Ca u+ cycling3, 5, 6 or other ionic bases, including K ÷ current and Na + current. However, other mechanisms, including different depolarization, could lead to markedly different repolarization and electrical alternans. However, neither the QRS in the ECG recording nor the AT in the MAP recording changed from beat to beat in this patient. Importantly, for T-wave alternans to occur in the surface ECG recording, there must be temporally electrical alternans of action potential duration throughout the heart (e.g., endocardial-epicardial, anterior-posterior). The temporally electrical alternans between the LV lateral wall and the RV septum recorded by MAP was closely relatd~ to the T-wave alternans in this patient. We demonstrated temporally electrical alternans by MAP recordings during T-wave alternans in a patient with congenital LQTS.
Volume 132, Number 3 American HeartJournal
Shimizu et al.
701
V1
Vs
LVlat MAP J
RVOT MAP kJ
RVsep MAP
I5 rnV I
1000msec
I
Fig. 2. Simultaneous recordings of ECG leads V 1 and V5 and monophasic action potential (MAP) from LVlat MAP, RVOT MAP, and RVsep MAP during T-wave alternans. Electrical alternans of RT were recorded at all MAP recording sites (LVlat MAP, 425 to 400 msec; RVOT MAP, 435 to 445 msec; RVsep MAP, 400 to 440 msec) associated with T-wave alternans in ECG leads V1 and Vs. Moreover, RT was longer in LVlat MAP (425 msec) than in RVsep MAP (400 msec) on first and third beats, whereas it was shorter in LVlat MAP (400 msec) than in RVsep MAP (440 msec) on the second and fourth beats, indicating temporally electrical alternans between these two sites. REFERENCES 1. Schwartz PJ, Malliani A. Electrical alternation of the T wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T syndrome. Am Heart J 1975;89:45-50. 2. Zareba W, Moss AJ, Cessie SL, Hall WJ. T wave alternans in idiopathic long QT syndrome. J Am Coll Cardiol 1994;23:1541-6. 3. Surawicz B, Fish C. Cardiac alternans: diverse mechanisms and clinical manifestations. J Am Coll Cardiol 1992;20:438-99. 4. Shimizu W, Ohe T, Kurita T, Takaki H, Aihara N, Kamakura S, et al. Early afterdepolarizations induced by isoproterenol in patients with congenital long QT syndrome. Circulation 1991;84:1915-23.
5. Lee H-C, Mohabir R, Smith N, Franz MR, Clusin WT. Effects ofischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1: correlation with monophasic action potentials and contraction. Circulation 1988;78:1047-59. 6. Verrier RL, Nearing BD. Electrophysiologic basis for T wave alternans as an index of vulnerability to ventricular fibrillation. J Cardiovasc Electrophysiol 1994;5:445-61.
Shimizu et al.
699
pl/==l
800
400 200
0 llA,.~,Li]~
INFLATION
DIII~%ATION
Figure 1. Atrial natriuretic peptide plasma concentrations in coronary sinus (black bars) and in peripheral v e i n (hatched bars) before, during, a n d a f t e r P T C A - i n d u c e d m y o c a r d i a l ischemia, p < 0.02.
possibly b e c a u s e of t h e s m a l l n u m b e r . I n t h e only p a t i e n t w i t h a n i n s i g n i f i c a n t i n c r e a s e (5%) in c o r o n a r y s i n u s A N F c o n c e n t r a t i o n d u r i n g i s c h e m i a left v e n t r i c u l a r end-diastolic p r e s s u r e did not change. A direct effect of e n d o t h e l i n on a t r i a l myocites h a s b e e n s u g g e s t e d as a n o t h e r m e c h a n i s m for A N P release; a n i n c r e a s e of e n d o t h e l i n level in a r t e r i a l blood h a s b e e n found i m m e d i a t e l y a f t e r PTCA. 5 O u r d a t a s h o w t h a t a f t e r r e p e r f u s i o n t h e fall in c o r o n a r y sinus A N F c o n c e n t r a t i o n occurs v e r y r a p i d l y a l t h o u g h t h e r e is no a p p r e c i a b l e v a r i a t i o n in p e r i p h e r a l v e i n A N P concentration. C h e n u et ah, 3 who m e a s u r e d A N P concent r a t i o n in a r t e r i a l blood, found a p e r s i s t e n c e of i n c r e a s e d A N P c o n c e n t r a t i o n 20 m i n u t e s a f t e r t h e l a s t balloon inflation. The d e c r e a s e in A N P c o n c e n t r a t i o n in a r t e r i a l a n d v e n o u s blood a p p e a r s to occur g r a d u a l l y a f t e r r e p e r f u s i o n in c o n t r a s t to t h e r a p i d fall in t h e c o r o n a r y s i n u s blood. I n fact, it h a s b e e n s h o w n t h a t t h e A N P c o n c e n t r a t i o n in a p e r i p h e r a l vein, i n c r e a s e d w i t h i n t r a v e n o u s infusion of A N P , r e t u r n s to b a s a l v a l u e s 25 m i n u t e s a f t e r t h e e n d of t h e infusion, s T h e c o r o n a r y s i n u s A N P c o n c e n t r a t i o n no doubt b e t t e r reflects t h e A N P r e l e a s e f r o m t h e myocites; a c h a n g e in A N P p r o d u c t i o n should be i m m e d i a t e l y followed by a r e s p e c t i v e c h a n g e in its c o r o n a r y sinus concentration, M o r e o v e r it m u s t be u n d e r s c o r e d t h a t A N P is found in t h e c o r o n a r y s i n u s blood in m u c h h i g h e r c o n c e n t r a t i o n s t h a n a f t e r dilution in t h e p e r i p h e r a l blood, as w a s also d e m o n s t r a t e d in our p a t i e n t s . T h e t r a n s i e n t m y o c a r d i a l i s c h e m i a i n d u c e d by P T C A is a powerful s t i m u l u s to A N P release, m a i n l y t h r o u g h t h e m e c h a n i s m of myocites s t r e t c h i n g because of i n c r e a s e d left a t r i a l p r e s s u r e c o n s e q u e n t to i s c h e m i c left v e n t r i c u l a r dysfunction. As soon as r e p e r f u sion is r e - e s t a b l i s h e d w i t h balloon deflation, A N F r e l e a s e r e t u r n s to b a s e l i n e level s i m u l t a n e o u s l y w i t h t h e functional r e c o v e r y of t h e left ventricle. REFERENCES
1. Ikaheimo MJ, Ruskoaho HJ, Airaksinen EJ, Huikuri HV, Korhonen UR, Leppaluoto PJ, et al. Plasma levels of atrial natriuretic peptide during myocardial ischemia induced by percutaneous translumina]
2. 3. 4. 5. 6.
7. 8.
coronary angioplasty or dynamic exercise. Am Heart J 1989;117:83741. Prachar H, Ogris E, Dittel M, Enenkel W. Rapid changes of atrial natriuretic peptide concentration during percutaneous transluminal coronary angioplasty. AMHEARTJ 1991;122:157-63. Chenu PC, Donckier JE, Schroeder E, Berbinski A, Ketelslegers JM, Marchandise B, et al. Atrial natriuretic factor during percutaneous transluminal coronary angioplasty. Acta Cardiol 1991;XLVI:595-603. Malatino LS, Leonardi C, Stancanelli B, Polizzi G, Grassi R, Tamburino C, et al. Transient myocardial ischemia stimulates atrial natriuretic factor release. Am Heart J 1992;123:693-8. Ameli S, Kaul S, Castro L, Arora C, Mirea A, Shah PK. Effect of percutaneous transluminal coronary angioplasty on circulating endothelin levels. Am J Cardiol 1993;72:1352-6. Sugawara A, Nakao K, Morii N, Sakamoto M, Suda M, Shimokura M, et al. Alpha-human atrial natriuretic peptide is released from the heart and circulates in the body. Biochem Biophys Res Commun 1985; 129:439-46. Anderson JV, Donckier J, McKenna WJ, BloomSR. The plasma release of atrial natriuretic peptide in man. Clin Sci 1986;71:151-5. Anderson JV, Donckier J, Payee NN, Beacham J, Slater JDH, Bloom SR. Atrial natriuretic peptide: evidence of action as a natriuretic hormone at physiological plasma concentrations in man. Clin Sci 1987;72:305-12.
Monophasic action potential recordings during T-wave alternans in congenital long QT syndrome W a t a r u S h i m i z u , MD, K a t s u h i k o Y a m a d a , MD, Yoshio A r a k a k i , MD, T e t s u r o K a m i y a , MD, a n d K a t s u r o S h i m o m u r a , M D Osaka, Japan From the Division of Cardiology, Department of Internal Medicine, and Department of Pediatrics, National Cardiovascular Center. Dr. Shimizu is supported in part by a grant from Japan Cardiovascular Research Foundation by Bayer Cardiovascular Disease Research Scholarship. Reprint requests: Wataru Shimizu, MD, Divisin of Cardiology,Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, Japan 565. Am Heart J 1996;132:699-701. Copyright © 1996 by Mosby-Year Book~Inc. 0002-8703/96/$5.00 + 0 4/4/~1988
700
September 1996 American Heart Journal
Shimizu et at.
III
,.F,~11my '
I
1 sec
Fig. 1. Six-lead electrocardiograms showing T-wave alternans during electrophysiologic study. Alternating changes in morphologic characteristics and polarity of the T wave were prominent in leads II, III, V1, and V5.
T-wave alternans is a rare but characteristic electrocardiographic (ECG) finding defined as alternating changes in the morphologic characteristics and polarity ofT waves in patients with congenital long QT syndrome (LQTS)fl 2 Twave alternans is thought to be related to spatial and temporal heterogeneity of repolarization from changes in action potential duration. 3 Monophasic action potential (MAP) has recently been used to detect membrane phenomena in beating hearts, and prolonged MAP duration and early afterdepolarization (EAD)-like activity have been demonstrated in congenital LQTS patients. 4 We recently recorded MAP during T-wave alternans in a patient with this syndrome. The patient was a 3-year-old boy with congenital LQTS who had QT prolongation (corrected QT interval [QTc] = 740 msecl/2). He had some episodes of stressinduced syncope and torsades de pointes, and spontaneous T-wave alternans was sometimes documented. His mother also had corrected QT interval prolongation. Electrophysiologic study was performed while the patient was sedated
with sodium pentobarbital (3 mg/kg) and diazepam (0.3 mg/kg) without antiarrhythmic drugs. MAP was recorded to examine the effects of intravenous antiarrhythmic drugs (e.g., verapamil or propranolol) directly on the action potential. All protocols were reviewed and approved by our Ethical Review Committee, and written informed consent was obtained from his parents. Two 6F MAP catheters (MAP pacing combination catheter, EP Technologies Inc., Sunnyvale, Calif.) were introduced through a femoral vein and advanced into the right ventricle, and one 6F MAP catheter was also introduced through a femoral artery and advanced into the left ventricle with fluoroscopic guidance. MAPs were simultaneously recorded from the left ventricular (LV) lateral wall (LVlat MAP), the right ventricular (RV) outflow tract (RVOT MAP), and the RV septum (RVsep MAP) with six surface ECG leads during sinus rhythm. Spontaneous T-wave alternans occurred during simultaneous MAP and ECG recordings. Six-lead ECG recording at a paper speed of 25 mm/sec showed typical T-wave alternans marked in leads II, III, V1 and V5 (Fig. 1). Fig. 2 shows simultaneous recordings from ECG leads V1 and V5 and MAPs from the same three sites at a paper speed of 100 mm/sec. The morphologic characteristics and duration of the QRS in the ECG recording and the activation time (AT) (the time between QRS onset and steep MAP upstroke) did not change from beat to beat. However, electrical alternans of the repolarization time (RT) (AT + MAP duration at 90% repolarization) were recorded at all MAP recording sites (LVlat MAP, 425 to 400 msec; RVOT MAP, 435 to 445 msec; RVsep MAP, 400 to 440 msec) associated with T-wave alternans in the ECG leads V1 and Vs: Moreover, temporally electrical alternans between the LVlat MAP and the RVsep MAP were demonstrated. That is, the RT of the first and third beats in Fig. 2 was longer in the LVlat MAP (425 msec) than in the RVsep MAP (400 msec), whereas the second and fourth beats had shorter RT in the LVlat MAP (400 msec) than in the RVsep MAP (440 msec). Although EAD-like activities were constantly recorded in the RVsep MAP, these activities were not directly related to the T-wave alternans in this patient. Several experimental studies suggested that electrical alternans depends on intracellular Ca u+ cycling3, 5, 6 or other ionic bases, including K ÷ current and Na + current. However, other mechanisms, including different depolarization, could lead to markedly different repolarization and electrical alternans. However, neither the QRS in the ECG recording nor the AT in the MAP recording changed from beat to beat in this patient. Importantly, for T-wave alternans to occur in the surface ECG recording, there must be temporally electrical alternans of action potential duration throughout the heart (e.g., endocardial-epicardial, anterior-posterior). The temporally electrical alternans between the LV lateral wall and the RV septum recorded by MAP was closely relatd~ to the T-wave alternans in this patient. We demonstrated temporally electrical alternans by MAP recordings during T-wave alternans in a patient with congenital LQTS.
Volume 132, Number 3 American HeartJournal
Shimizu et al.
701
V1
Vs
LVlat MAP J
RVOT MAP kJ
RVsep MAP
I5 rnV I
1000msec
I
Fig. 2. Simultaneous recordings of ECG leads V 1 and V5 and monophasic action potential (MAP) from LVlat MAP, RVOT MAP, and RVsep MAP during T-wave alternans. Electrical alternans of RT were recorded at all MAP recording sites (LVlat MAP, 425 to 400 msec; RVOT MAP, 435 to 445 msec; RVsep MAP, 400 to 440 msec) associated with T-wave alternans in ECG leads V1 and Vs. Moreover, RT was longer in LVlat MAP (425 msec) than in RVsep MAP (400 msec) on first and third beats, whereas it was shorter in LVlat MAP (400 msec) than in RVsep MAP (440 msec) on the second and fourth beats, indicating temporally electrical alternans between these two sites. REFERENCES 1. Schwartz PJ, Malliani A. Electrical alternation of the T wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T syndrome. Am Heart J 1975;89:45-50. 2. Zareba W, Moss AJ, Cessie SL, Hall WJ. T wave alternans in idiopathic long QT syndrome. J Am Coll Cardiol 1994;23:1541-6. 3. Surawicz B, Fish C. Cardiac alternans: diverse mechanisms and clinical manifestations. J Am Coll Cardiol 1992;20:438-99. 4. Shimizu W, Ohe T, Kurita T, Takaki H, Aihara N, Kamakura S, et al. Early afterdepolarizations induced by isoproterenol in patients with congenital long QT syndrome. Circulation 1991;84:1915-23.
5. Lee H-C, Mohabir R, Smith N, Franz MR, Clusin WT. Effects ofischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1: correlation with monophasic action potentials and contraction. Circulation 1988;78:1047-59. 6. Verrier RL, Nearing BD. Electrophysiologic basis for T wave alternans as an index of vulnerability to ventricular fibrillation. J Cardiovasc Electrophysiol 1994;5:445-61.