Transmembraneous dislocation of myocardial S100A1 calcium-binding protein during ischaemia and reperfusion: a new marker of myocardial damage during cardiac surgery

Introduction

Despite myocardial protection, ischaemia during cardiopulmonary bypass induces greater or lesser degrees of damage to cardiomyocytes as a result of transient cytosolic calcium overload. Recently, increasing attention has been paid to the role of heart-specific calcium-binding proteins in the pathogenesis of myocardial ischaemia-reperfusion injury. S100A1 is a heart-specific EF-hand calcium-binding protein, which is directly involved in a variety of calcium-mediated processes in human myocytes.

Method

In order to elucidate the feasibility of using S100A1 calcium-binding protein for monitoring extended periods of ischaemia, we attempted to characterize the ultrastructural localization of S100A1 in the human heart under normal conditions (baseline), after prolonged ischaemia and after reperfusion. Confocal laser scanning microscopy was used to study cardiac biopsies taken at these three time points, during cardiopulmonary bypass in patients undergoing elective cardiac surgery.

Results

Tissue samples obtained before initiation of extracorporeal circulation showed that S100A1 localized in the cytoplasm, which was strictly associated with actin contractile filaments. Ischaemia of the heart (≥ 30 min) induced specific dislocation of S100A1 to the cell membrane and the interstitial space. However, this dislocation was reversible after reperfusion (≥ 30 min).

Conclusion

These data suggest that S100A1 may be associated with transient perioperative myocardial damage despite cardioplegia in the human heart. This protein, which is involved in the regulation of contractile function of muscle cells, may be an important intracellular marker for ischaemia-reperfusion injury of the heart.