From the Division of Cardiology, Department of Internal Medicine,
National Cardiovascular Center, Osaka, Japan (W.S., T.K., K.M., K. Suyama,
N.A., S.K., K. Shimomura), and the Little Frank Abercrombie Section of
Cardiology, Department of Pediatrics and Department of Molecular and Human
Genetics, Baylor College of Medicine, Houston, Tex (J.A.T.)
Correspondence to Wataru Shimizu, MD, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501-1787. E-mail shimizu{at}mmrl.edu
Background—This study used
monophasic action potential (MAP) to examine the effect of nicorandil,
a K+ channel opener, on repolarization abnormalities
induced by epinephrine in the LQT1 form of congenital long-QT
syndrome in which the KvLQT1 mutation underlies the
defect in the channel responsible for the slowly activating component
of the delayed rectifier potassium current.
Methods and Results—MAPs were recorded
simultaneously from two or three sites on the right
ventricular and left ventricular endocardium in
6 patients with a congenital form of LQT1 syndrome with
KvLQT1 defect (17 sites) and 8 control patients (24
sites). In LQT1 patients, epinephrine infusion prolonged the QT
interval and 90% MAP duration (MAPD90) and increased the
dispersion of MAPD90. Epinephrine also induced
early afterdepolarizations (EADs) as well as ventricular
premature complexes (VPCs) in 2 of the 6 patients. Nicorandil during
epinephrine infusion abbreviated the QT interval and
MAPD90, decreased the dispersion of MAPD90, and
abolished the EADs as well as the VPCs in 1 patient. Addition of
propranolol completely reversed the effect of
epinephrine in prolonging the QT interval and
MAPD90 and increasing the dispersion and eliminated the
EADs and VPCs in another patient. In control patients, the effect of
epinephrine and that of additional nicorandil and
propranolol on repolarization parameters were
much less than in the LQT1 patients.
Conclusions—Our results suggest that nicorandil, a K+
channel opener, improves repolarization abnormalities in the LQT1 form
of congenital long-QT syndrome with KvLQT1 defect.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Improvement of Repolarization Abnormalities by a K+ Channel Opener in the LQT1 Form of Congenital Long-QT Syndrome
Key Words: long-QT syndrome • potassium • receptors, adrenergic, beta • depolarizing • action potentials
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