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J Thorac Cardiovasc Surg 1997;113:576-584
© 1997 Mosby, Inc.
CARDIOPULMONARY BYPASS, |
Supported by grants from the Selander Fund, the University Hospital, Uppsala, the Uppsala County Association Against Heart and Lung Diseases, and the Swedish Medical Research Council (project B96-13X-11568-01A).
Received for publication August 6, 1996 revisions requested Sept. 5, 1996; revisions received Sept. 30, 1996 accepted for publication Oct. 29, 1996. Address for reprints: Agneta Siegbahn, MD, PhD, Department of Clinical Chemistry, University Hospital, S-751 85 Uppsala, Sweden.
Abstract
Objectives: Cardiopulmonary bypass is associated with extensive thrombin generation and cell activation. Our main hypothesis in this study was that the expression of tissue factor on circulating monocytes contributes to the formation of thrombin. Methods: Markers of activation of the coagulation cascade and cell activation were measured in 26 patients undergoing elective heart operations randomized to the use of heparin-coated (Duraflo II, n = 13) or standard cardiopulmonary bypass circuits (n = 13). Results: Thrombin generation, measured as the thrombin-antithrombin complex, increased considerably during cardiopulmonary bypass with peak levels 3 hours afterward and with remaining elevation 20 hours later. Despite increased monocyte and granulocyte activation and increased levels of monocyte chemotactic protein-1, which upregulates monocyte tissue factor expression in vitro, monocyte tissue factor expression was not increased at the end of cardiopulmonary bypass. Furthermore, at this time the monocytes were less sensitive to in vitro stimulation by endotoxin. These results might be explained by simultaneous enhanced levels of interleukin-10, which effectively downregulates monocyte tissue factor expression in vitro. Twenty hours after cardiopulmonary bypass was discontinued, the tissue factor expression on freshly isolated monocytes and on monocytes stimulated by endotoxin was significantly increased compared with preoperative levels. At this time increased activation markers of granulocytes, monocytes, and lymphocytes were also recorded. None of the measured parameters was found to be different between the groups. Conclusions: The tissue factor expression on circulating monocytes is upregulated the day after heart operations. The clinical relevance and the regulatory mechanism behind the enhanced expression, however, are not fully elucidated.
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