Effects of the ATP-sensitive K channel opener nicorandil on the QT interval and the effective refractory period in patients with congenital long QT syndrome. Investigator Group for K-Channel Openers and Arrhythmias.
Congenital or idiopathic long QT syndrome is characterized by a frequently lethal ventricular arrhythmia called torsades de pointes (TdP) as well as a prolonged QT interval. The long QT interval related to an abnormal gene of the Na+ channel has been shown to be shortened by mexiletine. However, the action of K+ channel openers on the QT interval associated with abnormal genes of the K channel has yet to be studied. Seven patients of five families with long QT syndrome were included in this study, of whom six had syncope and six had documented TdP. Either long QT interval or sudden cardiac death had been observed in family members of all seven patients. At 1 to 3 weeks after admission, when TdP or frequent ventricular arrhythmia had subsided, nicorandil, an ATP-sensitive K channel opener, was administered orally at a dose of 15 mg/day in five patients and at 30 mg/day in the remaining two patients, and the effects were assessed on the third day after drug administration. In four patients, the effective refractory period was measured in the right ventricle before and after administration of K channel opener administration. The QT interval (QTc) prior to administration of the K channel opener was 0.60 +/- 0.09 ms (mean +/- SD) (0.61 +/- 0.10 second(1/2)), which was shortened to 0.54 +/- 0.05 ms (0.55 +/- 0.06 second(1/2)) on the third day of drug administration (P < .05 for both): 10.4 +/- 8.0% (8.6 +/- 5.5%). The QT interval at varying preceding R-R intervals on Holter electrocardiograms showed a shift toward the right as a result of the drug administration. The effective refractory period showed a significant prolongation, 256 +/- 26 ms versus 280 +/- 22 ms before and after drug administration, respectively (P <.05). Intravenous administration of nicorandil resulted in no significant change in heart rate or blood pressure, while QTc showed a tendency to shorten, but nonsignificantly (P = .08). However, a hump on the monophasic action potential was abolished, especially at the long preceding R-R interval induced by premature stimulation of the ventricle. It is concluded that nicorandil shortens the QT interval slightly when administered orally, whereas the effective refractory period shows a slight prolongation. The physiologic and clinical significance of these effects needs to be studied further.
Aizawa
Y
Y
First Department of Internal Medicine, Niigata University School of Medicine, Japan.
Uchiyama
H
H
Yamaura
M
M
Nakayama
T
T
Arita
M
M
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D015716:Electrocardiography, Ambulatory / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008133:Long QT Syndrome / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020108:Nicorandil; D015221:Potassium Channels / Q000819:agonists*; D016171:Torsades de Pointes / Q000188:drug therapy / Q000235:genetics
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D009536:Niacinamide; D020108:Nicorandil