ORIGINAL ARTICLES: CARDIOVASCULAR
Leukocyte integrin expression in patients undergoing cardiopulmonary bypass

https://doi.org/10.1016/S0003-4975(99)01553-2Get rights and content

Abstract

Background. The recruitment of leukocytes to vascular endothelium is controlled by adhesion events mediated through the β2 integrins, whereas the response of extravasated leukocytes within the tissues is controlled through the β1 integrins. Although cardiopulmonary bypass (CPB) has been shown to be associated with a systemic inflammatory response and elevated levels of β2 integrins on leukocytes, its effect on the β1 integrins is not known. This study investigated the effect of the protease inhibitor aprotinin on the expression of the β1 and β2 integrins on circulating leukocytes in patients undergoing CPB.

Methods. Patients undergoing primary elective coronary artery bypass grafting were randomized into full-dose aprotinin or placebo groups. Blood samples were obtained at nine time points preoperatively, intraoperatively, and up to 6 days postoperatively. The surface expression of the β1 integrins VLA-1, -3, -4, -5, and -6 and of the β2 integrins CD11a/CD18, CD11b/CD18, and CD11c/CD18 was measured by flow cytometry on gated neutrophil and monocyte subpopulations in whole blood.

Results. Expression of the β1 integrins was not significantly altered during the study period and, therefore, aprotinin had no effect on the expression of these molecules. Of the β2 integrins, CD11b/CD18 expression was significantly increased on neutrophils at 15 minutes after onset of CPB in the placebo group (p < 0.01) but not in the aprotinin group.

Conclusions. This study showed that expression of the β1 integrins on neutrophils and monocytes did not alter during the first 6 days after CPB. Expression of the β2 integrin CD11b/CD18 increased significantly on neutrophils during CPB in control patients but not in patients treated with full-dose aprotinin.

Section snippets

Patient groups

The protocol of the study was approved by our Ethical Committee and informed consent was obtained from all patients. Eighteen patients, undergoing primary elective coronary artery bypass grafting (CABG), were randomized into two groups in a double-blind fashion. One group (n = 8) received full-dose aprotinin [2] and the other group (n = 10) served as a control. Patients were excluded from the study if they met any of the following criteria: episodes of unstable angina or myocardial infarction

Intraoperative and postoperative characteristics of patients

There was no significant difference between aprotinin and placebo groups with regard to number of grafts, CPB time, and cross-clamp time (Table 1). All patients received internal thoracic artery graft to the left anterior descending artery. Patients in the aprotinin group lost significantly less blood through the chest drains and received significantly less blood transfusions at 12 hours postoperatively (Table 1). Patients in the two groups had a similarly low rate of postoperative

Comment

Neutrophil activation, adhesion to endothelium, and extravasation are decisive steps in the systemic inflammatory response. Activated neutrophils, along with their bactericidal effects, also may contribute significantly to injury of inflamed tissue [11]. Adhesion molecules play an important role during inflammation on both sides of the endothelial barrier, first by helping to recruit leukocytes from the vascular compartment to the vessel wall and subsequently by modulating their responsiveness

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