Quinidine elicits proarrhythmic changes in ventricular repolarization and refractoriness in guinea-pig
Quinidine is a class Ia Na+ channel blocker that prolongs cardiac repolarization owing to the inhibition of I Kr, the rapid component of the delayed rectifier current. Although quinidine may induce proarrhythmia, the contributing mechanisms remain incompletely understood. This study examined whether quinidine may set proarrhythmic substrate by inducing spatiotemporal abnormalities in repolarization and refractoriness. The monophasic action potential duration (APD), effective refractory periods (ERPs), and volume-conducted electrocardiograms (ECGs) were assessed in perfused guinea-pig hearts. Quinidine was found to produce the reverse rate-dependent prolongation of ventricular repolarization, which contributed to increased steepness of APD restitution. Throughout the epicardium, quinidine elicited a greater APD increase in the left ventricular chamber compared with the right ventricle, thereby enhancing spatial repolarization heterogeneities. Quinidine prolonged APD to a greater extent than ERP, thus extending the vulnerable window for ventricular re-excitation. This change was attributed to increased triangulation of epicardial action potential because of greater APD lengthening at 90% repolarization than at 30% repolarization. Over the transmural plane, quinidine evoked a greater ERP prolongation at endocardium than epicardium and increased dispersion of refractoriness. Premature ectopic beats and monomorphic ventricular tachycardia were observed in 50% of quinidine-treated heart preparations. In summary, abnormal changes in repolarization and refractoriness contribute greatly to proarrhythmic substrate upon quinidine infusion.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
Document Type: Research Article
Affiliations: Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
Publication date: January 1, 2013
More about this publication?
- Published since 1929, this monthly journal reports new research in the fields of physiology and pharmacology.
- Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Sign up for journal newsletters
- Ingenta Connect is not responsible for the content or availability of external websites