Inteplay of Trigger CA2+ Waves and CA2+ Transient Alternans in Atrial Myocytes

We previously documented triggered calcium (Ca) wave (TCW) development in atrial myocytes from large animals during rapid pacing. The goal of this study was to investigate the relationship between Ca transient (CaT) alternans and TCWs in atrial myocytes from normal and failing hearts. Ca cycling was measured via confocal microscopy in atrial myocytes isolated from normal and failing canine hearts then loaded with Ca-sensitive fluorescent dyes. Normal atrial myocytes (NAMs; n = 84) or heart failure atrial myocytes (HFAMs; n = 162) were stimulated at increasingly rapid rates leading to TCW development at rates ≥ 3Hz in ∼54% of NAMs, but often at lower rates and with greater incidence in ∼88% HFAMs. TCW development was contingent on retaining high SR load with diastolic Ca rising 10-20% above that at basal pacing (1Hz) and fractional Ca-release (FCR) being ≈ 0.5 early during rapid pacing epochs. TCWs failed to develop if such FCR was or became ≪ 0.5. However, if such FCR was or became ≫ 0.5, typically few if any TCWs developed or previously developed TCWs ceased, and either larger magnitude TCW-negative CaTs or CaT alternans developed. Overall, CaT alternans developed in ∼29% of NAMs and ∼24% of HFAMs. Additionally, large TCWs often exhibited a periodicity of about 1 per 4-5 pacing cycles, thus manifesting as large slow-rate CaTs superimposed on small rapid-rate CaTs. In summary, atrial myocytes are predisposed to TCW formation during rapid pacing. Significantly increasing FCR is effective in abrogating TCWs, but often leads to the development of CaT alternans in their stead. Our data suggest that TCWs could cause early afterdepolarizations and, along with Ca alternans, could promote dispersion of repolarization, thus promoting atrial arrhythmogenesis (such as atrial fibrillation) particularly in the setting of heart failure.