Modulation of ventricular fibrillation in isolated perfused heart by dofetilide.
The authors studied the involvement of IKr potassium current in ventricular fibrillation during perfusion. Electrophysiologic parameters were measured before and after dofetilide administration (2.5, 7.5, and 12.5 x 10-7 M, n = 8) in isolated perfused feline hearts. During pacing, these parameters included epicardial conduction time, refractoriness, and the fastest rate for 1:1 pacing/response capture. During 8 minutes of electrically induced tachyarrhythmias, they included heart rate and normalized entropy reflecting the degree of organization. In all groups, arrhythmia rate was slower in the right ventricle than in the left ventricle. Dofetilide decreased the arrhythmia rate more than it increased organization, reduced its maintenance, or increased difficulty in initiation. Refractoriness was prolonged in a reverse use-dependent way which was less than 1:1 pacing/response capture. Unexpectedly, a moderate prolongation of conduction time was observed. Inverse correlation was found between the arrhythmia rate and changes in refractoriness and conduction time and between the degree of organization and refractoriness (both ventricles) and conduction time (right ventricle). Dofetilide, which intensively blocks IKr current and unexpectedly suppressed conduction, has different quantitative effects on fibrillation features. These changes in fibrillation suggest that these effects are mainly associated with refractoriness prolongation and do not seem to be attenuated by conduction suppression.
Amitzur
Giora
G
Neufeld Cardiac Research Institute, Sheba Medical Center, Tel Hashomer 52621, Israel. ncri@sheba.health.gov.il
Shenkar
Nitza
N
Leor
Jonathan
J
Novikov
Ilia
I
Eldar
Michael
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D027682:Cation Transport Proteins; D002415:Cats; D022062:Electrophysiologic Techniques, Cardiac; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D015425:Myocardial Reperfusion; D010627:Phenethylamines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C063533:dofetilide