Direct evidence of endothelial injury during cardiopulmonary bypass by demonstration of circulating endothelial cells

Abstract

Endothelial activation is considered a key process in the development of a whole body inflammatory response secondary to cardiopulmonary bypass (CPB). Increased levels of a multitude of soluble mediators have been described as being released during and after cardiac surgery. Circulating endothelial cells have recently been established as a novel marker of endothelial damage in a variety of vascular disorders.

Blood samples from 20 patients undergoing elective coronary artery bypass surgery were obtained preoperatively and 1, 6, 12, 24, and 48 h after termination of CPB. Control samples were obtained from ten healthy volunteers. Circulating endothelial cells (CEC) were isolated with immunomagnetic anti-CD146-coated Dynabeads, and counted in a Nageotte chamber.

Low numbers of CEC were observed in healthy control volunteers (12±6 cells/mL; median: 9 cells/mL). CEC numbers were already significantly elevated in all patients before CPB, and there was a further significant increase after weaning from CPB (maximum increase at 6 h after CPB: 73±30 cells/mL; range: 30-153 cells/mL, p < 0.001).

The number of CEC provides further and direct evidence that CPB is associated with a pronounced endothelial injury and/or damage. CEC appear to be most useful markers for vascular endothelial activation because they are specific, stable, and circulating components of injured vessel wall.

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References

Steinberg JB , Kapelanski DP , Olson JD , Weiler JM. Cytokine and complement levels in patients undergoing cardiopulmonary bypass . J Thorac Cardiovasc Surg 1993; 106: 1008-1016 .

Menasche P , Haydur S , Paynet J et al. A potential mechanism of vasodilation after heart surgery: the temperature-dependent release of cytokines . J Thorac Cardiovasc Surg 1994; 107: 293-299 .

Eikemo H , Sellevold OFM , Videm V. Markers for endothelial activation during open heart surgery . Ann Thorac Surg 2004; 77: 214-219 .

Woywodt A , Streiber F , De Groot K , Regelsberger H , Haller H , Haubitz M. Circulating endothelial cells as markers for ANCA-associated small vessel vasculitis . Lancet 2003; 361: 206-210 .

Dignat-George F , Sampol J. Circulating endothelial cells in vascular disorders: new insights into an old concept . Eur J Haematol 2000; 65: 215-220 .

Van Mourik JA , Boertjes R , Huisveld IA et al. Von Willebrand factor propeptide in vascular disorders: a tool to distinguish between acute and chronic endothelial cell perturbation . Blood 1999; 94: 179-185 .

Lo B , Fijnheer R , Castigliego D et al. Activation of haemostasis after coronary artery bypass grafting with or without cardiopulmonary bypass . Anesth Analg 2004; 99: 634-640 .

Royston D. Blood cell activation . Sem Thorac Cardiovasc Surg 1990; 2/4: 341-357 .

Chong AY , Blann AD , Lip GY. Assessment of endothelial damage and dysfunction: observations in relation to heart failure . Q J Med 2003; 96: 253-267 .

10.

Butler J , Rocker GM , Westaby S. Inflammatory response to cardiopulmonary bypass . Ann Thorac Surg 1993; 55: 552-559 .

11.

Andresen TK , Svennevig JL , Videm V. Soluble VCAM- 1 is a very early marker of endothelial cell activation in cardiopulmonary bypass . Perfusion 2002; 17: 15-21 .

12.

Boyle EM , Pohlman TH , Johnson MC et al. The systemic inflammatory response . Ann Thorac Surg 1997; 64: S31-S37 .

13.

Makin AJ , Blann AD , Chung NAY et al. Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells . Eur Heart J 2004; 25: 371-376 .

14.

Mutin M , Canavy I , Blann A , Bory M , Sampol J. Evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulation endothelial cells . Blood 1999; 93: 2951-2958 .

15.

Blann AD. Endothelial cell activation, injury, damage and dysfunction: separate entities or mutual terms ? Blood Coagul Fibrinolysis 2000; 11: 623-630 .