Inflammatory Cell Findings in the Female Rabbit Heart and Stress-associated Exacerbation with Handling and Procedures Used in Nonclinical Studies

Autor: William J. Reagan, David W. Clarke, George Hu, Richard Perry, Ingrid D. Pardo, K Nasir Khan, Jennifer Colangelo, Rani S. Sellers, Victoria Markiewicz, Cynthia M. Rohde
Rok vydání: 2017
Předmět:
medicine.medical_specialty
Pathology
Urinalysis
Exacerbation
040301 veterinary sciences
Hydroxycorticosteroids
medicine.medical_treatment
Drug Evaluation
Preclinical
Cardiomyopathy
Physiology
Sodium Chloride
Toxicology
Injections
Intramuscular
030226 pharmacology & pharmacy
Pathology and Forensic Medicine
0403 veterinary science
03 medical and health sciences
Catecholamines
0302 clinical medicine
Species Specificity
Internal medicine
Toxicity Tests
medicine
Animals
Myocytes
Cardiac
Interventricular septum
Molecular Biology
Saline
Hematology
medicine.diagnostic_test
biology
business.industry
Macrophages
Myocardium
04 agricultural and veterinary sciences
Cell Biology
medicine.disease
Epinephrine
medicine.anatomical_structure
Leukocytes
Mononuclear
biology.protein
Female
Creatine kinase
Rabbits
business
Biomarkers
Stress
Psychological
medicine.drug
Zdroj: Toxicologic Pathology. 45:416-426
ISSN: 1533-1601
0192-6233
Popis: Despite the use of rabbits in biomedical research, including regulatory toxicology and cardiovascular studies, little data exist on heart findings in this species. This study was designed to document myocardial findings in female rabbits and the impact of study-related procedures typical for vaccine toxicology studies. One hundred and forty 6- to 8-month-old female New Zealand White rabbits were divided equally into 2 groups, high and low study procedure groups (group 1 and group 2, respectively). All animals received intramuscular (IM) injections of sterile saline every 2 weeks for 5 times and were necropsied 2 days after the final IM injection. Clinical chemistry, hematology, and urinalysis were evaluated. Blood for stress biomarkers (norepinephrine, epinephrine, cortisol, and corticosterone), C-reactive protein, cardiac troponin I, and creatine kinase were collected at time 0 (just before dose administration) and then at 4, 24, and 48 hr after dose administration in group 1 only. Hearts were assessed histologically. Focal to multifocal minimal inflammatory cell infiltrates were common (∼80%), particularly in the left ventricle and interventricular septum, and were similar to the types of infiltrates identified in other laboratory animal species. Additionally, study-related procedures elevated serum stress biomarkers and exacerbated the frequency and severity of myocardial inflammatory cell infiltrates.
Databáze: OpenAIRE
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