Effects of Fluid Treatment in a B. Anthracis Lethal Toxi

在最近的B爆发中，休克对常规液体和血管加压药治疗的抵抗在死亡者中很常见。炭疽病在美国在先前的研究中，虽然血压降低类似于致死性脂多糖（LPS）和炭疽杆菌致死毒素（LeTx）的挑战，血浆细胞因子和一氧化氮水平，而增加与LPS与LeTx。这一数据和其他数据表明，LeTx休克的发病机制可能与脓毒症和脓毒性休克患者中常见的细菌毒素类型不同。LeTx电击对常规血流动力学支持的反应是否不同也应该考虑。 本研究的目的是比较传统的血流动力学支持在用LeTx、LPS或E.大肠杆菌在这项研究的一个阶段已经完成，我们表明，液体支持，而增加血压和改善生存与LPS和E。大肠杆菌，恶化这些与LeTx的模式，显着不同。此外，液体支持否定了LeTx定向单克隆抗体的有益作用。LeTx激发期间液体低氧血症恶化为该治疗的不利影响提供了一个基础。 我们现在已经扩展了这些研究，目前正在比较LeTx与LPS激发的动物中去甲肾上腺素血管加压治疗的效果。在这些研究中，我们发现去甲肾上腺素确实会增加LPS和LeTx的血压，但前者可以提高生存率，而后者则没有。因此，再一次，具有LPS激发的预期有益效果的常规血液动力学治疗不具有LeTx。进一步的研究正在进行中，以确定在LeTx和LPS激发期间内源性儿茶酚胺反应的差异是否为去甲肾上腺素对结果的不同影响提供了基础。 然而，总体而言，目前的研究结果提出了关于传统血流动力学支持对LeTx相关休克的有效性的问题。因为这种毒素在B期的休克中起着关键作用。炭疽病更好地定义这些治疗在活细菌感染期间的作用可能是重要的。已经提交了一篇论文供出版，描述了上面概述的流体实验。血管加压药研究以摘要形式提交。

Shock resistant to conventional treatment with fluid and vasopressors was common in nonsurvivors in the recent outbreak of B. anthracis infection in the US. In prior studies, although blood pressure was reduced similarly with lethal lipopolysaccharide (LPS) and Bacillus anthracis lethal toxin (LeTx) challenges, plasma cytokine and nitric oxide levels, while increased with LPS were not with LeTx. This and other data suggests that the pathogenesis of shock with LeTx may differ from the types of bacterial toxin commonly encountered in patients with sepsis and septic shock. Whether the response of LeTx shock to conventional hemodynamic support differs as well should be considered. The purpose of the present study has been to compare the effects of conventional hemodynamic support in rats challenged with LeTx, LPS or E. coli bacteria. In one phase of this study now completed, we showed that fluid support, while increasing blood pressure and improving survival with LPS and E. coli, worsened these with LeTx in patterns that differed significantly. Furthermore, fluid support negated the beneficial effects of LeTx directed monoclonal antibodies. Worsened hypoxemia with fluids during LeTx challenge provide one basis for the detrimental effects of this treatment. We have now extended these studies and are presently comparing the effects vasopressor treatment with norepinephrine in animals challenged with LeTx versus LPS. In these studies we found that while norepinephrine does increase blood pressure with both LPS and LeTx, it improves survival with the former but not thelatter toxin. Once again therefore, a conventional hemodynamic treatment which has the expected beneficial effects with LPS challenge, does not with LeTx. Further studies are underway determining whether differences in the endogenous catecholamine response during LeTx and LPS challenge provide a basis for the differing effects of norepinephrine on outcome. Overall however the present findings raise questions regarding the effectiveness of conventional hemodynamic support for LeTx associated shock. Since this toxin plays a key role in shock during B. anthracis better defining the role of these treatments during live bacterial infection may be important. A paper has been submitted for publication describing the fluid experiments outlined above. Vasopressor studies are being submitted in abstract form.