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Pathology of the Cardiovascular System

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Abstract

The cardiovascular system is present throughout the body and is therefore exposed to a wide range of potential toxicants. In preclinical toxicity studies for new compounds, the toxicologic pathologist plays an important role in detecting toxicities in the heart and blood vessels. Numerous compounds are associated with cardiovascular toxicity. Adrenergic and vasodilatory compounds are one such example; dogs are very sensitive to these compounds and develop lesions such as hemorrhage and inflammation in the heart and blood vessels. Some antineoplastic medications, most notably anthracyclines, are toxic to the cardiovascular system. Certain drugs with agonism for the serotonin receptor 5-HT2B are associated with proliferative lesions affecting the heart valves. There are many other mechanisms of cardiovascular toxicity as well.

Spontaneous findings in the cardiovascular system often mimic compound-induced toxicities. The pathologist must be aware of these spontaneous findings and often must use a weight-of-evidence approach to differentiate these findings from compound-induced toxicities. In addition to examining gross and histologic specimens, the pathologist often interprets cardiovascular biomarker, organ weight, and cardiovascular safety pharmacology data to detect compound-induced toxicities and differentiate them from spontaneous lesions. Most importantly, the pathologist must communicate how the findings in a preclinical toxicity study may apply to human beings or veterinary patients for whom the compound is being developed.

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Acknowledgments

The authors would like to thank Gary Gintant and Karen Bodié for their review of this chapter.

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Authors and Affiliations

  1. Charles River Laboratories, Inc., Mattawan, MI, USA

    Joshua H. Decker

  2. AbbVie Inc., North Chicago, IL, USA

    Radhakrishna Sura

  3. Experimental Pathology Laboratories, Inc., West Lafayette, IN, USA

    Paul W. Snyder

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  1. Joshua H. Decker
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  2. Radhakrishna Sura
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  3. Paul W. Snyder
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Correspondence to Joshua H. Decker .

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Editors and Affiliations

  1. North Carolina Laboratory, Experimental Pathology Laboratories, Inc., Durham, NC, USA

    Thomas J. Steinbach

  2. Charles River Laboratories, Inc., Mattawan, MI, USA

    Daniel J. Patrick

  3. MEC Regulatory and Toxicology Consulting, LLC, Moorpark, CA, USA

    Mary Ellen Cosenza

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Decker, J.H., Sura, R., Snyder, P.W. (2019). Pathology of the Cardiovascular System. In: Steinbach, T., Patrick, D., Cosenza, M. (eds) Toxicologic Pathology for Non-Pathologists. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9777-0_8

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