title: Contribution of mechanical factors to arrhythmogenesis in calcium overloaded cardiomyocytes: model predictions and experiments.
abstract: It is well-known that Ca²⁺ overload in cardiomyocytes may underlie arrhythmias. However, the possible contribution of mechanical factors to rhythm disturbances in Ca²⁺ overloaded myocytes has not been sufficiently investigated. We used a mathematical model of the electrical and mechanical activity of cardiomyocytes to reveal an essential role of the mechanisms of cardiac mechano-electric feedback in arrhythmogenesis in Ca²⁺ overloaded myocardium. In the model, the following mechanical factors increased Ca²⁺ overload in contracting cardiomyocytes and promoted rhythm disturbances: i) a decrease in the mechanical load for afterloaded contractions; and ii) a decrease in the initial length of sarcomeres for isometric twitches. In exact accordance with the model predictions, in experiments on papillary muscles from the right ventricle of guinea pigs with Ca²⁺ overloaded cardiomyocytes (using 0.5-1 μM of ouabain), we found that emergence of rhythm disturbances and extrasystoles depends on the mechanical conditions of muscle contraction.
authors.affiliation: Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, 106 Pervomayskaya str, Ekaterinburg 620049, Russian Federation. l.katsnelson@iip.uran.ru
authors.forename: Leonid B
authors.initials: LB
authors.lastname: Katsnelson
authors.forename: Olga
authors.initials: O
authors.lastname: Solovyova
authors.forename: Alexander
authors.initials: A
authors.lastname: Balakin
authors.forename: Oleg
authors.initials: O
authors.lastname: Lookin
authors.forename: Pavel
authors.initials: P
authors.lastname: Konovalov
authors.forename: Yuri
authors.initials: Y
authors.lastname: Protsenko
authors.forename: Tatiana
authors.initials: T
authors.lastname: Sulman
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Markhasin
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D055595:Mechanical Phenomena; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
chemical_list: D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium