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

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.

Beclomethasone dipropionate and chronic asthma. The effect of long-term aerosol administration on the hypothalamic-pituitary-adrenal axis after substitution for oral therapy with corticosteroids.

Beclomethasone dipropionate aerosol at a dose of 100 mug four times a day was administered to 32 patients suffering from chronic perennial asthma. Twenty-three of these patients had previously received prolonged treatment with corticosteroids, causing various degrees of adrenal suppression in some patients. Almost complete recovery of adrenal function was observed within a period of six months in most patients. Treatment with beclomethasone dipropionate did not affect the hypothalamic-pituitary-adrenal axis in the other nine asthmatic patients who had not received prolonged corticosteroid therapy previously and who served as a control group.