Arrhythmogenic [Ca^<2+>]_i dynamics of the pefused heart revealed by confocal microscopy

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Abnormal intracellular Ca^<2+> ([Ca^<2+>]_i) handling, which deyelops under Ca^<2+> overloaded conditions of the heart by e.g., ischemia-reperfusion injury, has been considered to be an important substrate for tachyarrhythmias. However, it is unknown whether and how altered [Ca^<2+>]_i dynamics of the injured heart contributes to the development of tachyarrhythmias. To address this question, we studied spatiotemporal changes in [Ca^<2+>]_i at the epicardial regions of the fluo-3/AM-loaded rat heart with and without cryo-injury using real-time confocal microscopy. The following results were obtained.1) Under quiescent conditions, the intact regions of the heart exhibited Ca^<2+> waves sporadically at 4 waves/min/cell, which were totally abolished by Ca^<2+> transients.2) The Ca^<2+> waves occurred more frequently as the heart was more highly Ca^<2+>-overloaded. The waves at the Ca^<2+>-overloaded regions (Ca^<2+>-overloaded waves) often propagated to the surrounding myocytes, whereas th … More e waves at highly damaged regions showed extremely high-frequency with neither cell-to-cell propagation nor abolition by Ca^<2+> transients.3) When cryo-injury was applied to the heart via liquid nitrogen, the border zones exhibited prevalent Ca^<2+> waves, in sharp contrast to the intact zones, where only homogeneous Ca^<2+> transients but no Ca^<2+> waves occurred. The border zones exhibited two different types of Ca^<2+> waves : the highly frequent Ca^<2+> waves (210/min/cell), which were unaffected by the surrounding Ca^<2+> transients, occurred at just adjacent to the cryo-necrosed regions, and the less frequent waves (79/min/cell), totally diminished by the transients, occurred at the vicinities.4) The frequent Ca^<2+> waves at the adjacent regions occurred asynchronously to either the intrinsic heart rhythm or high-frequency (2-3 Hz) excitation, whereas the less-frequent waves at the vicinities occurred more frequently and prevalently as the heart was stimulated at higher frequencies.These observations may represent abnormal [Ca^<2+>]_i handling during acute myocardial injury. The Ca^<2+> waves at the injured regions may become a substrate for triggered arrhythmias and contractile failure. Less