Does QT widening in the Langendorff-perfused rat heart represent the effect of repolarization delay or conduction slowing?
It has been suggested that class I antiarrhythmic drugs and ischemia can widen the QT interval in the Langendorff-perfused rat heart preparation as a consequence of slowed ventricular conduction. If this were so, it would undermine the clinical relevance of the preparation and its effectiveness as an antiarrhythmic bioassay. To test this, the authors determined whether three different class I drugs could prolong QT in the preparation and whether this effect was augmented by ischemia and elevation of the potassium (K+) content of the perfusion solution. Baseline drug-free QT intervals correlated inversely with the K+ content (3 microM vs. 5 mM). QT intervals widened during the first 3-5 minutes of ischemia (P < 0.05), then returned gradually to baseline. Lidocaine (3.88 microM and 12.93 microM) had no effect on the QT interval before or during ischemia, whereas quinidine (7.90 microM but not 0.79 microM) and flecainide (1.48 microM but not 0.74 microM) caused QT widening before and during ischemia (P < 0.05). Elevating perfusion solution K+ content from 3 microM to 5 mM reduced the QT-widening effects of quinidine and flecainide (P < 0.05). Because lidocaine, a relatively selective sodium (Na+) channel blocker, failed to widen QT interval whereas quinidine and flecainide (combined Na+ and K+ channel blockers) did so, and because K+ elevation reduced rather than potentiated the drug-induced QT widening, it is unlikely that Na+ channel blockade and conduction slowing play any role in ischemia- or class I drug-induced QT widening in this model.
Second Department of Internal Medicine and Cardiology Centre, Faculty of Medicine, University of Szeged, Hungary.
András
A
Farkas
Michael J
MJ
Curtis
D000818:Animals; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008133:Long QT Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D010477:Perfusion / Q000379:methods*; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology
D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D011188:Potassium