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 microm/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.