The roles of gaseous mediators during inflammatory cytokine induced cardiac depression

基础研究采用大鼠工作心脏预备法，探讨气体分子(一氧化氮、一氧化碳、一氧化碳)在肿瘤坏死因子-α(肿瘤坏死因子-α)和白介素1-β(IL-Iβ)诱导的心脏抑制中的作用及相互关系。细胞因子的应用降低了左心室做功(LVW)。给予一氧化氮合酶抑制剂L-刀豆素(CaN)和一氧化碳合成酶(血红素氧合酶)抑制剂锌原卟啉(ZPP)改善左心室重量。心肌组织中诱导型一氧化氮合酶(INOS)和诱导型一氧化氮合酶(HO-1)基因表达在灌流后2小时显著升高。给予CaN抑制HO-1的表达，给药ZPP抑制HO-1的表达，促进iNOS的表达。这些数据表明，尽管NOS/NO系统和HO/CO系统在基因表达水平上相互关联，但这两个系统对心肌收缩性能的相互作用并不清楚，其他因素在这种情况下可能是重要的。临床研究通过检测CO-Hb浓度和循环血中HO的表达以及肿瘤坏死因子-α和IL-1β的表达来改变冠状动脉搭桥术中CO生成的变化。手术后CO-Hb显著升高；然而，在术前CO-Hb[大于或等于]1.0%的患者中，这些值没有显著变化。术后HO-1、肿瘤坏死因子-α和IL-1β的表达明显增加。CO-Hb与炎症介质的表达比例显著相关；然而，在术前CO-Hb[大于或等于]1.0%的患者中，相关性较低。这些数据表明，一般来说，CO-Hb可以反映手术的炎症反应；然而，CO-Hb作为手术应激标志物的有效性可能仅限于某些患者。

<Basic research> Using the rat working heart preperation, the role and relation of gaseous molecules (nitric oxide, NO ; carbon monoxide, CO) during tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-Iβ) induced cardiac depression. Administration of cytokines depressed the left ventricular work (LVW). Administrations of NO synthase (NOS) inhibitor, L-canavanin (CAN) and CO synthase (hemeoxygenase) inhibitor, zinc protoporphyrine (ZPP) improved the LVW. Gene expressions of inducible NOS (iNOS) and inducible HO (HO-1) in the left ventricle significantly increased 2 hours after perfusion. Administration of CAN inhibited the increase of HO-1 expression, and adminstration, of ZPP inhibited the HO-1 expression and promoted the INOS expression. These data suggest that NOS/NO systema and HO/CO system are interrelated at the gene ezpression levels even when those systems are highly promoted, however, the interaction of both systems on cardiac contractility did not make clear and other factors are speculated to be important under those situation. <Clinical research> Changes in CO generation during coronary artery bypass graft by measuring CO-Hb concentrations and the expression of HO in circulating blood as well as the expressions of TNF-α and IL-1β. CO-Hb significantly increased after surgery ; however, those values did not significantly change in patients who showed CO-Hb 【greater than or equal】1.0% before surgery. The expression ratios of HO-1, TNF-α, and IL-1β significantly increased after surgery. CO-Hb significantly correlated with the expression ratios of the inflammatory mediators ; however, the correlation was low in the patients who showed CO-Hb 【greater than or equal】1.0% before surgery. These data indicate that CO-Hb can, in general, reflect the surgical inflammatory response ; however, the usefulness of CO-Hb as a marker of surgical stress might be limited to certain patients.