Pro- and antiarrhythmic effects of fast cardiac pacing in a canine model of acquired long QT syndrome.
Increasing the heart rate is one option for suppressing bradycardia-dependent polymorphic ventricular tachycardias (PVTs). The mechanisms underlying preventive pacing in acquired forms of the long QT syndrome (LQTs) are still not fully understood. Using two needle electrodes, local effective refractory periods (ERPs) were determined in the left (LV) and right ventricle (RV) in 20 dogs with acute AV node ablation before continuous pacing, during a 20-min period of continuous fast pacing (Cl 300 ms, fastpac) and during a 35-min recovery period with slow (Cl 500 ms) pacing. This protocol was applied to control dogs (5 dogs) and dogs with pretreatment of the IKs blocking agent chromanol 293b (5 dogs, LQTs1), the IKr-blocking agent dofetilide (5 dogs, LQTs2) or a combination thereof (5 dogs). Fastpac resulted in a significant abbreviation of ERPs in control dogs and dogs receiving dofetilide or chromanol 293b. During recovery, shortening of ERPs persisted in the control group, but diminished in dogs with acquired LQTs. In dogs with LQTs2 fastpac could not suppress inhomogeneity of refractoriness during recovery. With pretreatment of dofetilide and chromanol 293b in combination, MAP duration during fastpac significantly increased (first beat: 256+/-6 ms vs. sixth beat: 278+/-9 ms, p<0.05) and fastpac-induced PVTs were evident. ERP shortening and reduced inhomogeneity of refractoriness might be one antiarrhythmic action of fastpac in dogs with acute AV-block. However, in the acquired LQTs1 and 2 beneficial effects of fastpac diminished and in a combination thereof fastpac-induced PVTs are likely.
Department of Cardiology, University of Heidelberg, Bergheimerstrasse 58, 69115 Heidelberg, Germany. alexander_bauer@med.uni-heidelberg.de
Alexander
A
Bauer
J Kevin
JK
Donahue
Frederik
F
Voss
Ruediger
R
Becker
Patricia
P
Kraft
Julia C
JC
Senges
Kamilla
K
Kelemen
Hugo A
HA
Katus
Wolfgang
W
Schoels
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006327:Heart Block / Q000503:physiopathology; D008133:Long QT Syndrome / Q000503:physiopathology*; D008297:Male; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D016276:Ventricular Function / Q000187:drug effects
D002839:Chromans; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; C063533:dofetilide