Phosphodiesterase type 4 inhibitor rolipram inhibits activation of monocytes during extracorporeal circulation.
Phosphodiesterase type 4 inhibitor rolipram inhibits activation of monocytes during extracorporeal circulation.
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DOI：
10.1016/j.jtcvs.2004.12.028
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发表时间：
2005-08
期刊：
影响因子：
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通讯作者：
Yukio Sato;Y. Hiramatsu;S. Homma;Makiko Sato;S. Sato;S. Endo;Y. Sohara
中科院分区：
文献类型：
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作者：
Yukio Sato;Y. Hiramatsu;S. Homma;Makiko Sato;S. Sato;S. Endo;Y. Sohara
目的体外循环与全身炎症反应综合征和激活的白细胞介导的多器官损伤风险相关。磷酸二酯酶4型是白细胞中主要的磷酸二酯酶同工酶，在调节白细胞活化中起着关键作用。为探讨选择性磷酸二酯酶4型抑制剂罗利普兰在模拟体外循环中对单核细胞功能的影响。方法与结果采用肝素化的人血在膜式氧合器上加或不加10μ/L的罗利普兰建立模拟体外循环。用流式细胞仪检测单核细胞L选择素和CD11b的表达。用酶免疫法测定C4D片段、BB片段、C5b-9、IL-6。罗利普兰可减少模拟体外循环对单核细胞CD11b表达的上调和对L选择素表达的降低。罗利普兰抑制C4D片段和IL-6的增加，但不影响BB片段和C5b-9的增加。结论罗利普兰抑制模拟体外循环中激活的单核细胞黏附分子表达和IL-6释放的变化。本研究提示，抑制磷酸二酯酶4型可能是预防体外循环患者过度炎症反应和器官损伤的可行治疗策略。
OBJECTIVECardiopulmonary bypass is associated with systemic inflammatory response syndrome and risk of multiorgan injury mediated by activated leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in leukocytes and plays a key role in the regulation of leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on functional changes of monocytes during simulated extracorporeal circulation.METHODS AND RESULTSSimulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with or without 10 μmol/L of rolipram. L-selectin and CD11b expression of monocytes were measured with flow cytometry. C4d fragment, Bb fragment, C5b-9, and interleukin-6 were measured with enzyme immunoassay. Rolipram reduced the increase in CD11b expression and the decrease in L-selectin expression of monocytes in response to simulated extracorporeal circulation. Rolipram inhibited the increase in C4d fragment and interleukin-6, but it did not affect the increase in Bb fragment or C5b-9.CONCLUSIONRolipram inhibited changes in adhesion molecule expression and interleukin-6 release by activated monocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be feasible therapeutic strategy to prevent exaggerated inflammatory response and organ injury in patients undergoing cardiopulmonary bypass.