Termination of equine atrial fibrillation by quinidine: an optical mapping study.
Abstract: To perform the first optical mapping studies of equine atrium to assess the spatiotemporal dynamics of atrial fibrillation (AF) and of its termination by quinidine. Methods: Intact, perfused atrial preparations obtained from four horses with normal cardiovascular examinations. Methods: AF was induced by a rapid pacing protocol with or without acetylcholine perfusion, and optical mapping was used to determine spatial dominant frequency distributions, electrical activity maps, and single-pixel optical signals. Following induction of AF, quinidine gluconate was perfused into the preparation and these parameters were monitored during quinidine-induced termination of AF. Results: Equine AF develops in the context of spatial gradients in action potential duration (APD) and diastolic interval (DI) that produce alternans, conduction block, and Wenckebach conduction in different regions at fast pacing rates. Quinidine terminates AF and prevents subsequent reinduction by reducing the maximal frequency and increasing frequency homogeneity. Conclusions: Heterogeneity of APD and DI promote alternans and conduction block at fast pacing rates in the equine atrium, predisposing to the development of AF. Quinidine terminates AF by reducing maximum frequency and increasing frequency homogeneity. Our results are consistent with the hypothesis that quinidine increases effective refractory period, thereby decreasing frequency.
Publication Date: 2008-11-25 PubMed ID: 19036667DOI: 10.1016/j.jvc.2008.10.002Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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The research study investigates how the drug quinidine impacts atrial fibrillation (AF), an irregular heart rhythm, in horse hearts. It uses optical mapping to visually track the actions of the heart before and after exposure to quinidine.
Methods
- The study used intact, perfused atrial preparations from four horses that had normal cardiovascular examinations to ensure a fair baseline.
- AF was induced via a rapid pacing protocol. This process could occur with or without perfusion of acetylcholine, a neurotransmitter often used to simulate nerve action.
- The team applied optical mapping to establish spatial dominant frequency distributions (the regions of most significant electrical activity), electrical activity maps (tracking the electrical signals of the heart), and single-pixel optical signals (detailed visualization of single interactions).
- After AF induction, quinidine gluconate, an AF treatment drug, was introduced and the parameters above were observed during and after the quinidine-induced termination of AF.
Results
- The study discovered that horse AF emerges within a context of spatial gradients in action potential duration (APD) and diastolic interval (DI), causing alternans (alternating patterns of electrical activity), conduction block (disrupted electrical signals), and Wenckebach conduction (irregular heartbeat pattern) in different regions when pacing rates are high.
- Quinidine terminates horse AF. Post application, it prevented subsequent reinduction, reducing the maximum frequency and increasing frequency homogeneity (evenness of heart rate).
Conclusions
- The research concluded that the heterogeneity or unevenness of APD and DI encourages alternans and conduction block at high pacing rates in the equine atrium, making it susceptible to AF development.
- Quinidine stops AF by lowering the top frequency and increasing frequency homogeneity.
- The results correlate with the theory that quinidine increases the effective refractory period–the period where the heart’s cells cannot immediately respond to another stimulation–thus reducing the overall frequency of heart rate.
Cite This Article
APA
Fenton FH, Cherry EM, Kornreich BG.
(2008).
Termination of equine atrial fibrillation by quinidine: an optical mapping study.
J Vet Cardiol, 10(2), 87-103.
https://doi.org/10.1016/j.jvc.2008.10.002 Publication
Researcher Affiliations
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
MeSH Terms
- Acetylcholine / pharmacology
- Action Potentials
- Animals
- Anti-Arrhythmia Agents / therapeutic use
- Atrial Fibrillation / drug therapy
- Atrial Fibrillation / veterinary
- Heart Atria / drug effects
- Horse Diseases / drug therapy
- Horses
- Quinidine / therapeutic use
- Tissue Culture Techniques / veterinary
Grant Funding
- HL075515-S03-S04 / NHLBI NIH HHS
Citations
This article has been cited 11 times.- Kappadan V, Sohi A, Parlitz U, Luther S, Uzelac I, Fenton F, Peters NS, Christoph J, Ng FS. Optical mapping of contracting hearts. J Physiol 2023 Apr;601(8):1353-1370.
- Iravanian S, Uzelac I, Cairns DI, Cherry EM, Kaboudian A, Fenton FH. Unimapper: An Online Interactive Analyzer/Visualizer of Optical Mapping Experimental Data. Comput Cardiol (2010) 2021 Sep;48.
- Shahi S, Marcotte CD, Herndon CJ, Fenton FH, Shiferaw Y, Cherry EM. Long-Time Prediction of Arrhythmic Cardiac Action Potentials Using Recurrent Neural Networks and Reservoir Computing. Front Physiol 2021;12:734178.
- Kappadan V, Telele S, Uzelac I, Fenton F, Parlitz U, Luther S, Christoph J. High-Resolution Optical Measurement of Cardiac Restitution, Contraction, and Fibrillation Dynamics in Beating vs. Blebbistatin-Uncoupled Isolated Rabbit Hearts. Front Physiol 2020;11:464.
- Eldaroti HH, Gadir SA, Refat MS, Adam AMA. Charge-transfer interaction of drug quinidine with quinol, picric acid and DDQ: Spectroscopic characterization and biological activity studies towards understanding the drug-receptor mechanism. J Pharm Anal 2014 Apr;4(2):81-95.
- Gizzi A, Cherry EM, Gilmour RF Jr, Luther S, Filippi S, Fenton FH. Effects of pacing site and stimulation history on alternans dynamics and the development of complex spatiotemporal patterns in cardiac tissue. Front Physiol 2013;4:71.
- Hsueh CH, Chang PC, Hsieh YC, Reher T, Chen PS, Lin SF. Proarrhythmic effect of blocking the small conductance calcium activated potassium channel in isolated canine left atrium. Heart Rhythm 2013 Jun;10(6):891-8.
- Swift LM, Asfour H, Posnack NG, Arutunyan A, Kay MW, Sarvazyan N. Properties of blebbistatin for cardiac optical mapping and other imaging applications. Pflugers Arch 2012 Nov;464(5):503-12.
- Cherry EM, Fenton FH, Gilmour RF Jr. Mechanisms of ventricular arrhythmias: a dynamical systems-based perspective. Am J Physiol Heart Circ Physiol 2012 Jun 15;302(12):H2451-63.
- Sabeh MK, Kekhia H, Macrae CA. Optical mapping in the developing zebrafish heart. Pediatr Cardiol 2012 Aug;33(6):916-22.
- Lou Q, Li W, Efimov IR. The role of dynamic instability and wavelength in arrhythmia maintenance as revealed by panoramic imaging with blebbistatin vs. 2,3-butanedione monoxime. Am J Physiol Heart Circ Physiol 2012 Jan 1;302(1):H262-9.
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