title: Intracellular calcium dynamics at the core of endocardial stationary spiral waves in Langendorff-perfused rabbit hearts.
abstract: In vitro models of sustained monomorphic ventricular tachycardia (MVT) are rare and do not usually show spiral reentry on the epicardium. We hypothesized that MVT is associated with the spiral wave in the endocardium and that this stable reentrant propagation is supported by a persistently elevated intracellular calcium (Ca(i)) transient at the core of the spiral wave. We performed dual optical mapping of transmembrane potential (V(m)) and Ca(i) dynamics of the right ventricular (RV) endocardium in Langendorff-perfused rabbit hearts (n = 12). Among 64 induced arrhythmias, 55% were sustained MVT (>10 min). Eighty percent of MVT showed stationary spiral waves (>10 cycles, cycle length: 128 +/- 14.6 ms) in the endocardial mapped region, anchoring to the anatomic discontinuities. No reentry activity was observed in the epicardium. During reentry, the amplitudes of V(m) and Ca(i) signals were higher in the periphery and gradually decreased toward the core. At the core, maximal V(m) and Ca(i) amplitudes were 42.95 +/- 5.89% and 43.95 +/- 9.46%, respectively, of the control (P < 0.001). However, the trough of the V(m) and Ca(i) signals at the core were higher than those in the periphery, indicating persistent V(m) and Ca(i) elevations during reentry. BAPTA-AM, a calcium chelator, significantly reduced the maximal Ca(i) transient amplitude and prevented sustained MVT and spiral wave formation in the mapped region. These findings indicate that endocardial spiral waves often anchor to anatomic discontinuities causing stable MVT in normal rabbit ventricles. The spiral core is characterized by diminished V(m) and Ca(i) amplitudes and persistent V(m) and Ca(i) elevations during reentry.
authors.affiliation: Krannert Institute of Cardiology, Indiana Univ. School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Gyo-Seung
authors.initials: GS
authors.lastname: Hwang
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ogawa
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.forename: Hrayr S
authors.initials: HS
authors.lastname: Karagueuzian
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004562:Electrocardiography; D004699:Endocardium / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D010477:Perfusion; D011817:Rabbits; D017180:Tachycardia, Ventricular / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D002614:Chelating Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid