Effects of Fluid Treatment in a B. Anthracis Lethal Toxin Challenged Rat Model

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。 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，虽然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，而后者则不能。值得注意的是，在这些研究中，内源性儿茶酚胺、一氧化氮和炎性细胞因子在LPS激发下显著升高，而在LeTx下显著升高。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。 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。

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. 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 the latter toxin. Of note in these studies endogenous catecholamines, nitric oxide, and inflammatory cytokines, while markedly elevated with LPS challenge, were with LeTx. Once again therefore, a conventional hemodynamic treatment which has the expected beneficial effects with LPS challenge, does not with LeTx. 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.