Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

02 July 2004

Atrial-selective antiarrhythmic actions of novel Ikur vs. Ikr, Iks, and IKAch class Ic drugs and beta blockers in pigs

Karsten Knobloch, Joachim Brendel, Björn Rosenstein, Markus Bleich, Andreas E. Busch, Klaus J. Wirth

Med Sci Monit 2004; 10(7): BR221-228 :: ID: 11700


Background:The Kv1.5 channel, underlying I[sub]Kur[/sub], is supposed to be atrial selective in pigs and humans. We investigated the effects of different potassium channel blockers, i.e. the IKur blockers AVE 0118, S9947 and S20951, with amiodarone (AM), dofetilide (DO), azimilide (AZ), ibutilide (IB), the I[sub]Ks[/sub] blocker HMR 1556, atropine (ATR), flecainide (FL), propafenone (PR), d,l-sotalol (SO), atenolol (ATE), and esmolol (ES), on the left and right atrial and ventricular refractoriness and left atrial vulnerability (LAV) in vivo in pigs.Material/Methods:In pentobarbital-anesthetized pigs (n=81), atrial and ventricular effective refractory periods (ERPs) were measured with the S1-S2-extrastimulus-method and QTc time from electrocardiograms. LAV was assessed after S2-extrastimulus to the left atrium.Results:All I[sub]Kur[/sub] blockers prolonged left stronger than right atrial ERP and did not change QTc. All I[sub]Kr[/sub] blockers predominantly prolonged the right vs. left atria. AM prolonged both atria equally, and ATR the left only. Pure beta blockers acted predominantly on the left atrium, as did FL and PR, while d,l-sotalol acted predominantly on the right. AVE 0118, S9947, S20951, ibutilide, and d,l-sotalol significantly decreased LAV (–100%, –100%, –82%, –53%, –42%; p<0.05), in contrast to all other drugs.
Conclusions: The IKur blockers exhibited stronger effects on the left atrium, which itself has shorter refractoriness, but strikingly with no effect on ventricular repolarization, while IKr blockers, IKs blockers, and d,l-sotalol exerted predominantly right atrial effects and known ventricular effects. IKur blockers inhibited atrial tachyarrhythmias stronger than all available drugs. Therefore, IKur blockers seem to be promising new atrial-selective antiarrhythmic drugs.

Keywords: Piperazines - pharmacology, Adrenergic beta-Antagonists - pharmacology, Amiodarone - pharmacology, Anti-Arrhythmia Agents - pharmacology, Atrial Function - physiology, Atropine - pharmacology, Biphenyl Compounds - pharmacology, Chromans - pharmacology, Flecainide - pharmacology, Heart Atria - drug effects, Imidazoles - pharmacology, Imidazolidines, Phenethylamines - pharmacology, Piperazines - pharmacology, Potassium Channel Blockers - pharmacology, Potassium Channels - physiology, Propafenone - pharmacology, Propanolamines - pharmacology, Sotalol - pharmacology, Sulfonamides - pharmacology, Swine, Ventricular Function - physiology

Add Comment 0 Comments


01 July 2024 : Editorial  

Editorial: The Global Threats of Increasing Antimicrobial Resistance Require New Approaches to Drug Development, Including Molecular Antimicrobial Adjuvants

Dinah V. Parums

DOI: 10.12659/MSM.945583

Med Sci Monit 2024; 30:e945583


In Press

Clinical Research  

Cost-Effectiveness Analysis of Hepatic Arterial Chemotherapy for Advanced Hepatocellular Carcinoma in China...

Med Sci Monit In Press; DOI: 10.12659/MSM.944526  


Clinical Research  

Comparative Analysis of Antihypertensive and Anticonvulsant Regimens in Managing Pre-eclampsia and Eclampsi...

Med Sci Monit In Press; DOI: 10.12659/MSM.944985  

Clinical Research  

Reduced Radial Artery Occlusion in Transradial Cerebral Angiography: Key Predictive Factors and Preventive ...

Med Sci Monit In Press; DOI: 10.12659/MSM.944297  

Database Analysis  

Enhanced Outcomes in Femoral Subtrochanteric Fractures Using Long INTERTAN Nails with Titanium Cable Cercla...

Med Sci Monit In Press; DOI: 10.12659/MSM.944383  

Most Viewed Current Articles

17 Jan 2024 : Review article   4,116,598

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799


14 Dec 2022 : Clinical Research   1,594,331

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990


16 May 2023 : Clinical Research   691,000

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387


01 Jan 2022 : Editorial   50,822

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952


Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750