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Toxicol Pathol ; 45(3): 416-426, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28349785

RESUMO

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.


Assuntos
Avaliação Pré-Clínica de Medicamentos , Macrófagos/imunologia , Miocárdio , Estresse Psicológico/imunologia , Testes de Toxicidade , Animais , Biomarcadores/sangue , Biomarcadores/urina , Catecolaminas/sangue , Catecolaminas/urina , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Hidroxicorticosteroides/sangue , Hidroxicorticosteroides/urina , Injeções Intramusculares , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Macrófagos/patologia , Miocárdio/citologia , Miocárdio/imunologia , Miocárdio/patologia , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/patologia , Coelhos , Cloreto de Sódio/administração & dosagem , Especificidade da Espécie , Estresse Psicológico/patologia , Testes de Toxicidade/métodos
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