Abstract 2627: Similarities and Differences in Subcellular Calcium Cycling Defects in Ischemia and Heart Failure
Background: Defects in excitation-contraction coupling have been intensely studied in isolated cardiac myocytes. However little is know as to if and/or how accurately the identified defects in intracellular calcium (Cai) cycling translate to that in fully coupled myocytes within the syncytium of the myocardium, particular in heart disease states.
Methods: Cai transients (CaTs) were measured in epicardial ventricular myocytes at the sarcomere level via confocal imaging of paced normal, globally ischemic and failing intact Langendorff-perfused rat hearts.
Results: Both ischemic and failing myocytes demonstrated prolonged CaT duration, increased CaT latency and decreased CaT amplitude when compared to controls. The heterogeneity of all CaT characteristics is increased in both ischemic and failing myocytes. In failing myocytes the heterogeneity is manifest between adjacent sarcomeres within the cell, while in ischemia it is manifest regionally across the cell. Heterogeneity in latency and duration both positively correlate with the development of subcellular CaT alternans, but the discordance complexity of subcellular CaT alternans is greater in failing vs. ischemic myocytes (see figures⇓ below).
Conclusions: Well-coupled normal, ischemic and failing myocytes all exhibit heterogeneity in sarcomeric Cai cycling; but the heterogeneity is exacerbated in ischemia and failure. While the sarcomeric Cai cycling heterogeneity in ischemia and failure is comparable, how it is manifest in each condition is disparate. These findings may be indicative of particular similarities and differences in mechanisms underlying arrhythmogenesis in ischemia and heart failure.