丙泊酚联合吲哚美辛对离体人肺内小动脉的影响

目的 探究丙泊酚与吲哚美辛联合使用对离体人肺内小动脉血管张力影响.方法 选取因肺肿瘤行肺叶切除手术的病人肿瘤周围正常肺组织作为实验标本,体式显微镜下分离人肺内小动脉将其分两组,丙泊酚组和丙泊酚联合吲哚美辛组,组内分为去内皮组和内皮完整组.使用微血管张力测定技术,丙泊酚组给予U46619使血管产生持续性收缩,张力平稳后,采用累计加药法加入丙泊酚(10～300 μmol/L);丙泊酚联合吲哚美辛组用吲哚美辛(100 μmol/L)预孵育30 min后,给予U46619使血管产生持续性收缩,张力平稳后,采用累计加药法加入丙泊酚(10～300 μmol/L),分别观察不同浓度丙泊酚对预收缩的人肺内小动脉张力的影响.结果 丙泊酚组丙泊酚对U46619预收缩人离体肺内小动脉产生低浓度(10～100 μmol/L)收缩高浓度(100～300 μmol/L)舒张双相作用,且去内皮组在低浓度产生收缩幅度(Emax=31.19±5.10％)高于内皮完整组(Emax=30.44±2.92％),P＜0.05.丙泊酚联合吲哚美辛组吲哚美辛可阻断丙泊酚引起的收缩反应,引起舒张反应最大舒张率内皮完整组(Emax=98.72±0.34％)高于去内皮组(Emax=94.56±0.53％),P＜0.05.结论 丙泊酚对经U46619收缩的人肺内小动脉呈低浓度收缩高浓度舒张双相作用,与吲哚美辛联合应用可以阻断其引起的肺血管收缩.收缩作用可能与丙泊酚增强肺动脉平滑肌环氧合酶活性,使环氧合酶源性收缩因子生成增多有关.舒张作用部分由内皮细胞参与.

Effects of propofol combined with indomethacin on contraction of isolated human pulmonary arteries

Objective To investigate the effects of propofol combined with indomethacin on the contractile function of isolated human pulmonary arteries.Methods Human pulmonary artery preparations were obtained from patients undergoing surgery for lung carcinoma.The intrapulmonary arteries were dissected and cut into rings under microscope for treatment with propofol or propofol combined with indomethacin.In each group,the rings were divided into endothelium-intact and endothelium-denuded groups and mounted in a Multi Myograph system.In propofol group,the rings were preconstricted by U46619 to induce a sustained contraction,and propofol (10-300 mmol/L) was then applied cumulatively.In the combined treatment group,the rings were pretreated with indomethacin (100 μmol/L) for 30 min before application of U46619 to induce sustained contraction,and propofol (10-300 μmol/L) was added cumulatively after the tension became stable.Results Propofol (10-100μmol/L) induced constrictions at low concentrations and caused relaxations at higher concentrations (100-300 μmol/L)in the pulmonary artery rings with prior U46619-induced contraction.Propofol caused stronger constrictions in endothelium-intact rings EC50=4.525±0.37,Emax=(30.44±2.92)％] than in endothelium-denuded rings EC50=4.699±0.12,Emax=(31.19±5.10)％,P＜0.05].Pretreatment of the rings with indomethacin abolished constrictions,and the relaxation was more obvious in endothelium-intact group pD2=3.713±0.11,Emax=(98.72±0.34)％] than in endothelium-denuded group pD2=3.54±0.03,Emax=(94.56±0.53)％,P＜0.05].Conclusion Propofol induces constriction at low concentrations and relaxation at high concentrations in human intrapulmonary arteries with U46619-induced contraction.Indomethacin abolishes the constriction induced by propofol in isolated intrapulmonary arteries,suggesting that propofol potentiates U46619-mediated pulmonary vasoconstriction by promoting the concomitant production of prostaglandin by cyclooxygenase in pulmonary artery smooth muscle cells,and the mechanism for its relaxation effect may partly depend on the endothelium.