A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 2 of 2)

Toxicol Pathol. 2017 Dec;45(8):1055-1066. doi: 10.1177/0192623317743948.


To test the diagnostic approach described in part 1 of this article, 2 exercises were completed by pathologists from multiple companies/agencies. Pathologist's examination of whole slide image (WSI) heart sections from rats using personal diagnostic approaches (exercise #1) corroborated conclusions from study #1. Using the diagnostic approach described in part 1, these pathologists examined the same WSI heart sections (exercise #2) to determine whether that approach increased consistency of diagnosis of rodent progressive cardiomyopathy (PCM) lesions. In exercise #2, there was improved consistency of categorization of small borderline morphologies and mild lesions, but a decrement in consistency of categorizing minimal lesions. Exercises 1 and 2 suggest the described diagnostic approach is representative of that in use by the majority of toxicologic pathologists across companies/agencies and that application by all may improve diagnostic consistency of PCM/like lesions. Additionally, a criterion of approximately 5% heart section involvement is suggested for separating mild from moderate or greater severity. While evidence is not absolute, until further investigation shows otherwise, microscopic changes resembling PCM, but located in the epicardial and subepicardial region of the right ventricle, may be considered as part of the spectrum of PCM.

Keywords: Sprague Dawley; cardiomyopathy; cardiovascular system; drug development; heart; rat pathology; rodent progressive cardiomyopathy.

MeSH terms

  • Animals
  • Cardiomyopathies / pathology*
  • Cardiomyopathies / veterinary
  • Cardiotoxicity / pathology
  • Cardiotoxicity / veterinary
  • Computer Simulation
  • Diagnostic Imaging / methods*
  • Diagnostic Imaging / standards
  • Diagnostic Imaging / veterinary
  • Disease Progression
  • Heart Ventricles / pathology*
  • Male
  • Rats, Sprague-Dawley*
  • Rodent Diseases / pathology*
  • Toxicity Tests / methods*
  • Toxicity Tests / veterinary