RATIONALE: Sarcoplasmic reticulum (SR) Ca(2+) cycling is key to normal excitation-contraction coupling but may also contribute to pathological cardiac alternans and arrhythmia. OBJECTIVE: To measure intra-SR free [Ca(2+)] ([Ca(2+)]SR) changes in intact hearts during alternans and ventricular fibrillation (VF). METHODS AND RESULTS: Simultaneous optical mapping of Vm (with RH237) and [Ca(2+)]SR (with Fluo-5N AM) was performed in Langendorff-perfused rabbit hearts. Alternans and VF were induced by rapid pacing. SR Ca(2+) and action potential duration (APD) alternans occurred in-phase, but SR Ca(2+) alternans emerged first as cycle length was progressively reduced (217±10 versus 190±13 ms; P<0.05). Ryanodine receptor (RyR) refractoriness played a key role in the onset of SR Ca(2+) alternans, with SR Ca(2+) release alternans routinely occurring without changes in diastolic [Ca(2+)]SR. Sensitizing RyR with caffeine (200 μmol/L) significantly reduced the pacing threshold for both SR Ca(2+) and APD alternans (188±15 and 173±12 ms; P<0.05 versus baseline). Caffeine also reduced the magnitude of spatially discordant SR Ca(2+) alternans, but not APD alternans, the pacing threshold for discordance, or threshold for VF. During VF, [Ca(2+)]SR was high, but RyR remained nearly continuously refractory, resulting in minimal SR Ca(2+) release throughout VF. CONCLUSIONS: In intact hearts, RyR refractoriness initiates SR Ca(2+) release alternans that can be amplified by diastolic [Ca(2+)]SR alternans and lead to APD alternans. Sensitizing RyR suppresses spatially concordant but not discordant SR Ca(2+) and APD alternans. Despite increased [Ca(2+)]SR during VF, SR Ca(2+) release was nearly continuously refractory. This novel method provides insight into SR Ca(2+) handling during cardiac alternans and arrhythmia.
RATIONALE: Sarcoplasmic reticulum (SR) Ca(2+) cycling is key to normal excitation-contraction coupling but may also contribute to pathological cardiac alternans and arrhythmia. OBJECTIVE: To measure intra-SR free [Ca(2+)] ([Ca(2+)]SR) changes in intact hearts during alternans and ventricular fibrillation (VF). METHODS AND RESULTS: Simultaneous optical mapping of Vm (with RH237) and [Ca(2+)]SR (with Fluo-5N AM) was performed in Langendorff-perfused rabbit hearts. Alternans and VF were induced by rapid pacing. SR Ca(2+) and action potential duration (APD) alternans occurred in-phase, but SR Ca(2+) alternans emerged first as cycle length was progressively reduced (217±10 versus 190±13 ms; P<0.05). Ryanodine receptor (RyR) refractoriness played a key role in the onset of SR Ca(2+) alternans, with SR Ca(2+) release alternans routinely occurring without changes in diastolic [Ca(2+)]SR. Sensitizing RyR with caffeine (200 μmol/L) significantly reduced the pacing threshold for both SR Ca(2+) and APD alternans (188±15 and 173±12 ms; P<0.05 versus baseline). Caffeine also reduced the magnitude of spatially discordant SR Ca(2+) alternans, but not APD alternans, the pacing threshold for discordance, or threshold for VF. During VF, [Ca(2+)]SR was high, but RyR remained nearly continuously refractory, resulting in minimal SR Ca(2+) release throughout VF. CONCLUSIONS: In intact hearts, RyR refractoriness initiates SR Ca(2+) release alternans that can be amplified by diastolic [Ca(2+)]SR alternans and lead to APD alternans. Sensitizing RyR suppresses spatially concordant but not discordant SR Ca(2+) and APD alternans. Despite increased [Ca(2+)]SR during VF, SR Ca(2+) release was nearly continuously refractory. This novel method provides insight into SR Ca(2+) handling during cardiac alternans and arrhythmia.
Authors: Aman Mahajan; Daisuke Sato; Yohannes Shiferaw; Ali Baher; Lai-Hua Xie; Robert Peralta; Riccardo Olcese; Alan Garfinkel; Zhilin Qu; James N Weiss Journal: Biophys J Date: 2008-01-15 Impact factor: 4.033
Authors: Vyacheslav M Shkryl; Joshua T Maxwell; Timothy L Domeier; Lothar A Blatter Journal: Am J Physiol Heart Circ Physiol Date: 2012-03-30 Impact factor: 4.733
Authors: Hugh Calkins; Gerhard Hindricks; Riccardo Cappato; Young-Hoon Kim; Eduardo B Saad; Luis Aguinaga; Joseph G Akar; Vinay Badhwar; Josep Brugada; John Camm; Peng-Sheng Chen; Shih-Ann Chen; Mina K Chung; Jens Cosedis Nielsen; Anne B Curtis; D Wyn Davies; John D Day; André d'Avila; N M S Natasja de Groot; Luigi Di Biase; Mattias Duytschaever; James R Edgerton; Kenneth A Ellenbogen; Patrick T Ellinor; Sabine Ernst; Guilherme Fenelon; Edward P Gerstenfeld; David E Haines; Michel Haissaguerre; Robert H Helm; Elaine Hylek; Warren M Jackman; Jose Jalife; Jonathan M Kalman; Josef Kautzner; Hans Kottkamp; Karl Heinz Kuck; Koichiro Kumagai; Richard Lee; Thorsten Lewalter; Bruce D Lindsay; Laurent Macle; Moussa Mansour; Francis E Marchlinski; Gregory F Michaud; Hiroshi Nakagawa; Andrea Natale; Stanley Nattel; Ken Okumura; Douglas Packer; Evgeny Pokushalov; Matthew R Reynolds; Prashanthan Sanders; Mauricio Scanavacca; Richard Schilling; Claudio Tondo; Hsuan-Ming Tsao; Atul Verma; David J Wilber; Teiichi Yamane Journal: Heart Rhythm Date: 2017-05-12 Impact factor: 6.343