In situ visualization of the intracellular Ca2+ dynamics at the border of the acute myocardial infarct

Ischemic insult to the heart produces myocyte Ca²⁺ (Ca²⁺]_i) overload. However, little is known about spatiotemporal changes in Ca²⁺]_i within the ischemic heart in situ at the cellular level. Using real-time confocal microscopy, we successfully visualized Ca²⁺]_i dynamics at the border zone on the subepicardial myocardium of the heart 2 h after coronary ligations followed by loading with fluo 3/AM. Three distinct regions were identified in the acute infarcted heart. In intact regions, the myocytes showed spatially uniform Ca²⁺ transients synchronously to QRS complex in the electrocardiogram. The myocytes at the infarcted regions showed no fluorescence intensity (FI). At the border zones between the intact and infarcted regions, Ca²⁺ waves emerged sporadically and randomly, instead of Ca²⁺ transients, at a mean frequency of 11.5 ± 8.5 min/cell with a propagation velocity of 151.0 ± 35.7 m/sec along the longitudinal axis of the individual myocytes. In addition, some myocytes within the border zone exhibited homogeneously high static FI, indicating severe Ca²⁺ overload. In summary, we provided the first direct evidence of abnormal Ca²⁺]_i dynamics in acute infarcted hearts at the cellular level. The observed diversity in spatiotemporal Ca²⁺]_i dynamics at the border zone may contribute to the arrhythmias or contractile failure in acute myocardial infarction.