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Electrophysiological effects of MS-551 in humans: a class III antiarrhythmic agent
S Isomoto1, A Konoe, O A Centurion
1Third Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Abstract:
To investigate the clinical effects of MS-551, a Class III antiarrhythmic agent, 11 patients underwent electrophysiological study. MS-551 was given intravenously as an initial dose of 0.2 or 0.3 mg/kg for 5 minutes followed by the continuous infusion at 0.2 or 0.3 mg/kg for 30 minutes, respectively, in all patients. The rate corrected QT interval increased significantly from 3 minutes after the beginning of MS-551 infusion. The sinus heart rate decreased significantly by 8% at 10 minutes after the drug administration (P < 0.025). Mean PR and QRS intervals, and blood pressure were not significantly affected by the drug. Mean PA, AH, and HV intervals during sinus rhythm were also not affected. The effective refractory periods (ERPs) of the atrium and ventricle were significantly prolonged by 13% from 202 +/- 24 ms to 231 +/- 26 ms (P < 0.0005), and by 7% from 238 +/- 11 ms to 257 +/- 13 ms (P < 0.002), respectively, by MS-551. The ERP of the atrioventricular node and sinoatrial nodal recovery time were not changed significantly by the drug. This is a report of the effects of MS-551 in humans. This agent could be useful for treatment of tachyarrhythmias by prolongation of ERPs of the atrium and ventricle without significant variations of blood pressure and intracardiac conduction times. It is noteworthy that MS-551 slightly but significantly decreased heart rate.
Insights
MS-551, a Class III antiarrhythmic, prolongs atrial and ventricular effective refractory periods (ERPs) in patients. This cardiac drug may treat tachyarrhythmias without affecting blood pressure or conduction, but it does decrease heart rate.
Area of Science:
- Clinical Electrophysiology
- Pharmacology
- Cardiology
Background:
- Class III antiarrhythmic agents are crucial for managing cardiac arrhythmias.
- Understanding the specific electrophysiological effects of novel agents like MS-551 is essential for clinical application.
Purpose of the Study:
- To evaluate the clinical electrophysiological effects of MS-551 in human patients.
- To determine the safety and efficacy of MS-551 in managing tachyarrhythmias.
Main Methods:
- Electrophysiological study in 11 patients administered intravenous MS-551.
- Dosage regimen included an initial bolus followed by continuous infusion.
- Assessment of various electrophysiological parameters including QT interval, heart rate, and effective refractory periods (ERPs).
Main Results:
- MS-551 significantly prolonged the rate-corrected QT interval.
- A significant decrease in sinus heart rate (8%) was observed.
- Effective refractory periods (ERPs) of the atrium and ventricle were significantly prolonged (13% and 7%, respectively).
- No significant changes in PR, QRS intervals, blood pressure, or AV nodal/sinoatrial nodal function were noted.
Conclusions:
- MS-551 demonstrates potential as an antiarrhythmic agent by prolonging atrial and ventricular ERPs.
- The drug appears safe for clinical use, with no significant impact on blood pressure or intracardiac conduction.
- MS-551 may be a valuable therapeutic option for tachyarrhythmias, with a noted effect of decreasing heart rate.