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

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...

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Autores principales: Suffredini, Dante A., Sampath-Kumar, Hanish, Li, Yan, Ohanjanian, Lernik, Remy, Kenneth E., Cui, Xizhong, Eichacker, Peter Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690141/
https://www.ncbi.nlm.nih.gov/pubmed/26703730
http://dx.doi.org/10.3390/toxins7124891
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author Suffredini, Dante A.
Sampath-Kumar, Hanish
Li, Yan
Ohanjanian, Lernik
Remy, Kenneth E.
Cui, Xizhong
Eichacker, Peter Q.
author_facet Suffredini, Dante A.
Sampath-Kumar, Hanish
Li, Yan
Ohanjanian, Lernik
Remy, Kenneth E.
Cui, Xizhong
Eichacker, Peter Q.
author_sort Suffredini, Dante A.
collection PubMed
description 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.
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spelling pubmed-46901412015-12-30 Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies Suffredini, Dante A. Sampath-Kumar, Hanish Li, Yan Ohanjanian, Lernik Remy, Kenneth E. Cui, Xizhong Eichacker, Peter Q. Toxins (Basel) Review 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. MDPI 2015-12-12 /pmc/articles/PMC4690141/ /pubmed/26703730 http://dx.doi.org/10.3390/toxins7124891 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Suffredini, Dante A.
Sampath-Kumar, Hanish
Li, Yan
Ohanjanian, Lernik
Remy, Kenneth E.
Cui, Xizhong
Eichacker, Peter Q.
Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies
title Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies
title_full Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies
title_fullStr Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies
title_full_unstemmed Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies
title_short Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial Function? A Review of Clinical Cases and Preclinical Studies
title_sort does bacillus anthracis lethal toxin directly depress myocardial function? a review of clinical cases and preclinical studies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690141/
https://www.ncbi.nlm.nih.gov/pubmed/26703730
http://dx.doi.org/10.3390/toxins7124891
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