Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies

Toxins

Dante A. Suffredini²  Hanish Sampath-Kumar²  Yan Li²  Lernik Ohanjanian²  Kenneth E. Remy¹  Xizhong Cui²  Peter Q. Eichacker² 

[1] Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA;Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA;

关键词: Bacillus anthracis;    anthrax;    lethal and edema toxins;    cardiovascular dysfunction;    shock;    treatment;   

DOI  :  10.3390/toxins7124891

来源: mdpi

【 摘 要 】

The US outbreak of B.anthracis infection in 2001 and subsequent cases in the US and Europe demonstrate that anthrax is a continuing risk for the developed world. While several bacterial components contribute to the pathogenesis of B. anthracis, production of lethal toxin (LT) is strongly associated with the development of hypotension and lethality. However, the mechanisms underlying the cardiovascular instability LT produces are unclear. Some evidence suggests that LT causes shock by impairing the peripheral vasculature, effects consistent with the substantial extravasation of fluid in patients dying with B. anthracis. Other data suggests that LT directly depresses myocardial function. However a clinical correlate for this latter possibility is less evident since functional studies and post-mortem examination in patients demonstrate absent or minimal cardiac changes. The purposes of this review were to first present clinical studies of cardiac functional and histologic pathology with B. anthracis infection and to then examine in vivo, in vitro, and ex vivo preclinical studies of LT’s myocardial effects. Together, these data suggest that it is unclear whether that LT directly depresses cardiac function. This question is important for the clinical management and development of new therapies for anthrax and efforts should continue to be made to answer it.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.