The roles of gaseous mediators during inflammatory cytokine induced cardiac depression

<基础研究> >利用大鼠工作心脏制备，气体分子（一氧化氮，NO，一氧化碳，CO）在肿瘤坏死因子-α (TNF-α)和白细胞介素-1β (IL-Iβ)诱导的心脏抑制中的作用和关系。细胞因子抑制左心室功（LVW）。给予NO合成酶（NOS）抑制剂、L-canavanin （CAN）和CO合成酶（血红素加氧酶）抑制剂、原卟啉锌（ZPP）均可提高LVW。灌注2 h后左心室诱导性NOS （iNOS）和诱导性HO （HO-1）基因表达显著升高。CAN抑制HO-1表达的增加，ZPP抑制HO-1表达，促进INOS表达。这些数据表明，NOS/NO系统和HO/CO系统在基因表达水平上是相互关联的，即使这些系统被高度提升，但两者对心脏收缩力的相互作用并不清楚，推测在这种情况下其他因素也很重要。<临床研究>通过测定循环血液CO- hb浓度、HO表达及TNF-α、IL-1β表达对冠状动脉搭桥术CO生成的影响。术后CO-Hb明显升高；然而，术前CO-Hb【大于或等于】1.0%的患者，这些值没有显著变化。术后HO-1、TNF-α、IL-1β表达率明显升高。CO-Hb与炎症介质的表达率显著相关；然而，术前CO-Hb【大于等于】1.0%的患者相关性较低。这些数据表明，CO-Hb通常可以反映手术炎症反应；然而，CO-Hb作为手术应激标志物的有用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.