title: Inflammatory Cell Findings in the Female Rabbit Heart and Stress-associated Exacerbation with Handling and Procedures Used in Nonclinical Studies.
abstract: 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.
authors.affiliation: 1 Drug Safety Research and Development, Pfizer Inc., Pearl River, New York, USA.
authors.forename: Rani S
authors.initials: RS
authors.lastname: Sellers
authors.affiliation: 2 Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pardo
authors.affiliation: 1 Drug Safety Research and Development, Pfizer Inc., Pearl River, New York, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hu
authors.affiliation: 2 Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: K Nasir
authors.initials: KN
authors.lastname: Khan
authors.affiliation: 2 Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Perry
authors.affiliation: 2 Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Markiewicz
authors.affiliation: 1 Drug Safety Research and Development, Pfizer Inc., Pearl River, New York, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rohde
authors.affiliation: 2 Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Colangelo
authors.affiliation: 2 Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA.
authors.forename: William
authors.initials: W
authors.lastname: Reagan
authors.affiliation: 1 Drug Safety Research and Development, Pfizer Inc., Pearl River, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Clarke
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002395:Catecholamines / Q000097:blood / Q000652:urine; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006889:Hydroxycorticosteroids / Q000097:blood / Q000652:urine; D007273:Injections, Intramuscular; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000276:immunology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000276:immunology / Q000473:pathology; D011817:Rabbits; D012965:Sodium Chloride / Q000008:administration & dosage; D013045:Species Specificity; D013315:Stress, Psychological / Q000276:immunology* / Q000473:pathology; D018675:Toxicity Tests / Q000379:methods
chemical_list: D015415:Biomarkers; D002395:Catecholamines; D006889:Hydroxycorticosteroids; D012965:Sodium Chloride
keywords: New Zealand White; animal models; cardiomyopathy; cardiovascular system; catecholamines; rabbit; risk assessment; stress