An intact, healthy vascular endothelium is coated by an endothelial glycocalyx (EG) of 0.4 - 0.5 mm thickness proving to be of importance for regulating inflammation and vascular permeability. 17 patients referred for elective coronary artery bypass surgery were prospectively randomized to on-pump conventional coronary artery bypass (CCAB, n=10) or off-pump coronary artery bypass surgery (OPCAB, n=7). Two components of the EG, syndecan-1 and heparan sulfate, were determined by ELISA in serum at various phases of the procedure. Moreover, saphenous veins left over after bypass grafting were immunohistochemically stained with antibodies for syndecan-1 or heparan sulfate. Basal concentrations of syndecan-1 and heparan sulfate were comparable in both groups (70 ng/ml and 11 mg/ml, resp.). Anesthesia and initiation of surgery caused no significant changes. Reperfusion of heart and lungs (CCAB) caused a 3-fold increase in syndecan-1 and a 2-fold increase in heparan sulfate. Surprisingly, in patients undergoing OPCAB, syndecan-1 and heparan sulfate also increased (6- and 2-fold, resp.). At the end of surgery, syndecan-1 and heparan sulfate had returned to basal in both groups. Immunohistochemical imaging substantiated that syndecan-1 and heparan sulfate are components of the human EG. This study now provides evidence for shedding of the EG in humans undergoing cardiac surgery.