Rate-dependent effect of verapamil on atrial refractoriness.
OBJECTIVE
The purpose of this study was to determine whether verapamil has rate-dependent effects on the atrial effective refractory period (AERP).


BACKGROUND
Block of calcium current (I(Ca)) and rapid component of the delayed rectifier potassium current (I(Kr)) by verapamil is frequency-dependent. This may result in variable effects of verapamil on the AERP, depending on the rate.


METHODS
The subjects of this study were 30 adults with a mean age of 45 +/- 13 years who did not have structural heart disease. In 20 subjects, the AERP was measured at basic drive cycle lengths (BDCLs) of 650 to 250 ms, in 50 ms decrements, before and after infusion of 0.1 mg/kg verapamil. The effective refractory periods (ERPs) were measured in the setting of autonomic blockade in 10 subjects and without autonomic blockade in 10 subjects. Ten subjects served as a control group and received a saline infusion instead of verapamil.


RESULTS
Verapamil significantly prolonged the AERP at BDCLs of 650 to 500 ms (p < 0.01 or p < 0.05) and significantly shortened the ERP at BDCLs of 300 and 250 ms (p < 0.01). In the control group, there were no significant differences between the baseline and post-saline measurements of ERP.


CONCLUSIONS
Verapamil prolongs AERP at slow rates and shortens AERP at rapid rates. These findings are consistent with a predominant effect on I(Ca) at rapid rates and a predominant effect on I(Kr) at slow rates.
Hassan
Sohail A
SA
Division of Cardiology, Department of Internal Medicine, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 49109-0022, USA.
Oral
Hakan
H
Scharf
Christoph
C
Chugh
Aman
A
Pelosi
Frank
F
Knight
Bradley P
BP
Strickberger
S Adam
SA
Morady
Fred
F
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D012720:Severity of Illness Index; D013617:Tachycardia, Supraventricular / Q000188:drug therapy* / Q000503:physiopathology*; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D015221:Potassium Channels; D014700:Verapamil