Ernofsson M, Thelin S, Siegbahn A
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
J Thorac Cardiovasc Surg. 1997 Mar;113(3):576-84. doi: 10.1016/S0022-5223(97)70373-8.
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.
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).
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.
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.
体外循环与广泛的凝血酶生成及细胞活化有关。本研究的主要假设是循环单核细胞上组织因子的表达有助于凝血酶的形成。
在26例行择期心脏手术的患者中，测量凝血级联反应激活和细胞活化的标志物，这些患者被随机分为使用肝素涂层（Duraflo II，n = 13）或标准体外循环回路（n = 13）。
以凝血酶 - 抗凝血酶复合物衡量的凝血酶生成在体外循环期间显著增加，术后3小时达到峰值水平，20小时后仍有升高。尽管单核细胞和粒细胞活化增加，且单核细胞趋化蛋白 - 1水平升高，后者在体外可上调单核细胞组织因子表达，但体外循环结束时单核细胞组织因子表达并未增加。此外，此时单核细胞对内毒素的体外刺激敏感性降低。这些结果可能由白细胞介素 - 10水平同时升高来解释，白细胞介素 - 10在体外可有效下调单核细胞组织因子表达。体外循环停止20小时后，与术前水平相比，新鲜分离的单核细胞以及经内毒素刺激的单核细胞上的组织因子表达显著增加。此时还记录到粒细胞、单核细胞和淋巴细胞的活化标志物增加。两组间未发现任何测量参数存在差异。
心脏手术后次日循环单核细胞上的组织因子表达上调。然而，这种增强表达背后的临床相关性和调节机制尚未完全阐明。
