Circulating endothelial cells and markers of endothelial damage after cardiac bypass

University of Cambridge (2004) J Physiol 555P, C14

Communications: Circulating endothelial cells and markers of endothelial damage after cardiac bypass

M.A. Barry*, E. Duggan†, T. Ryan† and C. Bell*

Departments of * Physiology, Trinity College Dublin and † Anaesthesia & Intensive Care Medicine, St James's Hospital, Dublin, Ireland

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Circulating endothelial cell (CEC) numbers rise in many cardiovascular disorders and have been interpreted as reflecting endothelial pathology (Dignat-George & Sampol, 2000). However, CECs also rise after exercise (O’Sullivan, 2003) and there is poor correlation between CECs and two plasma markers of endothelial damage, von Willebrand factor (vWF) and thrombomodulin (TM) (O’Sullivan, 2003; Barry, 2004; Tansey, 2004). It is also unknown whether CECs originate from systemic or pulmonary systems and the extent to which they recirculate. To gain more information on these points, we have measured arterial and venous CEC numbers and viability and plasma vWF and TM, in 15 patients (64 ± 2 years) undergoing cardiopulmonary bypass, which preferentially damages pulmonary endothelium (Kotani et al. 2000).

Patients were recruited from the Coronary Care Unit at St James’s Hospital. With institutional ethics approval and written informed consent, jugular venous and radial arterial samples were taken immediately before surgery and 1 and 6 h after cessation of bypass. CECs were isolated by differential centrifugation and stained with cresyl violet for cell counts or with trypan blue to detect viability. Plasma vWF and TM were assayed by ELISA. Results were corrected for peri-operative haemodilution and analysed with ANOVA or paired t tests.

Pre-operative plasma vWF was 2-fold higher and TM was 3-fold lower than in normal middle-aged individuals (see Barry, 2004). Both these markers rose during the bypass period (vWF pre 390 ± 25, 1 h post 595 ± 35 Units; TM pre 1.1 ± 0.2, 1 h post 3.5 ± 0.5 ng ml-1, means ± S.E.M.) and the increases were sustained over the 6 h post-bypass period (P < 0.01). Pre-operative CEC numbers were closely similar in venous and arterial bloods (201 ± 53 and 217 ± 65 cells ml-1) and around 2-fold higher than in healthy controls (see Barry, 2003). By 6 h post-bypass, CECs showed a non-significant downward trend. At the same time point, there was a rise in viable venous CECs (35 ± 7 from 24 ± 5 %, P < 0.05) with no change in arterial viability.

Our data demonstrate that in cardiac patients, as in normal individuals, there is lack of correlation between CEC numbers and plasma levels of vWF or TM. The absence of an arteriovenous CEC gradient indicates that these cells recirculate freely. The selective rise in viable cells in venous blood after bypass suggests that they originate preferentially from the systemic rather than the pulmonary circulation.



Where applicable, experiments conform with Society ethical requirements.

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