Cardiovascular System

Heart - Hemorrhage

Narrative
Comment:
Hemorrhage consists of few to many small, irregular foci of extravasated erythrocytes scattered within the myocardium (Figure 1, Figure 2, Figure 3, and Figure 4). Myocardial hemorrhage may be accompanied by other morphologic manifestations of myocardial damage (i.e., necrosis, macrophage infiltration). The presence of hemorrhage and cellular necrosis may indicate vascular damage or vasoconstriction of small arterial vessels, or may represent myocytic toxicity. Hemosiderin-laden macrophages may be seen.
Recommendations:
Heart - Hemorrhage should be diagnosed and graded based on the extent of the lesion. The distribution of the hemorrhage (e.g., focal, multifocal, or diffuse), as well as the location (i.e., right ventricle, left ventricle, atrium, myocardium, papillary muscle), should be described in the narrative. If hemorrhage is secondary to another process such as inflammation or necrosis, it should not be diagnosed separately unless warranted by severity.
References:

Greaves P. 2000. Cardiovascular system. In: Histopathology of Preclinical Toxicity Studies (Greaves P, ed). Elsevier, Amsterdam, 254-311.

Jokinen MP, Boyle M, Lieuallen WG, Johnson CL, Malarkey DE, Nyska A. 2011. Morphologic aspects of rodent cardiotoxicity in a retrospective evaluation of National Toxicology Program studies. Toxicol Pathol 39(5):850-860.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/21747121

Nyska A, Murphy E, Foley JF, Collins BJ, Petranka J, Howden R, Hanlon P, Dunnick JK. 2005. Acute hemorrhagic myocardial necrosis and sudden death of rats exposed to a combination of ephedrine and caffeine. Toxicol Sci 83:388-396.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/15537744
  • Image of hemorrhage in the heart from a male F344/N rat in a acute study

    Heart - Hemorrhage in a male F344/N rat from an acute study. Extravasated erythrocytes are present in the myocardium (arrows).

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<p>Heart - Hemorrhage in a male F344/N rat from an acute study. Extravasated erythrocytes are present in the myocardium (arrows).</p>

Heart - Hemorrhage in a male F344/N rat from an acute study. Extravasated erythrocytes are present in the myocardium (arrows).
<p>Heart - Hemorrhage in a male F344/N rat from an acute study (higher magnification of Figure 1). Extravasated erythrocytes separate cardiomyocytes (arrows).</p>

Heart - Hemorrhage in a male F344/N rat from an acute study (higher magnification of Figure 1). Extravasated erythrocytes separate cardiomyocytes (arrows).
<p>Heart - Hemorrhage in a male B6C3F1/N mouse from a subchronic study. Large areas of extravascular red blood cells are present in the myocardium (arrows).</p>

Heart - Hemorrhage in a male B6C3F1/N mouse from a subchronic study. Large areas of extravascular red blood cells are present in the myocardium (arrows).
<p>Heart - Hemorrhage in a male B6C3F1/N mouse from a subchronic study (higher magnification of Figure 3). Large areas of extravascular erythrocytes separate cardiomyocytes (arrows).</p>

Heart - Hemorrhage in a male B6C3F1/N mouse from a subchronic study (higher magnification of Figure 3). Large areas of extravascular erythrocytes separate cardiomyocytes (arrows).

Authors:

Crystal L. Johnson, DVM, DACVP
Veterinary Pathologist II
Charles River Laboratories, Inc.
Research Triangle Park, NC

Abraham Nyska, DVM, Diplomate ECVP, Fellow IATP
Expert in Toxicologic Pathology
Visiting Full Professor of Pathology
Sackler School of Medicine, Tel Aviv University Timrat Israel

Reviewers:

Brian Berridge, DVM, PhD, DACVP
Director, WW Animal Research Strategy
GlaxoSmithKline R&D
Research Triangle Park, NC

Mark F. Cesta, DVM, PhD, DACVP
Staff Scientist, NTP Pathologist
Cellular and Molecular Pathology Branch
Division of the National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC