title: Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies.
abstract: 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.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. dante.suffredini@nih.gov.
authors.forename: Dante A
authors.initials: DA
authors.lastname: Suffredini
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. hanishsampathkumar@gmail.com.
authors.forename: Hanish
authors.initials: H
authors.lastname: Sampath-Kumar
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. yli3@cc.nih.gov.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. lernik.ohanjanian@nih.gov.
authors.forename: Lernik
authors.initials: L
authors.lastname: Ohanjanian
authors.affiliation: Division of Critical Care Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. Remy_K@kids.wustl.edu.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Remy
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. CXizhong@cc.nih.gov.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. PEichacker@cc.nih.gov.
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin
keywords: Bacillus anthracis; anthrax; cardiovascular dysfunction; lethal and edema toxins; shock; treatment