RESPIRATORY SYSTEM

RESPIRATORY SYSTEM

The effects of potential therapeutics on the respiratory system can be assessed using a variety of models, and species, with which Porsolt has extensive experience. These models can be used for assessing the efficacy and/or safety of compounds, and include models for airway function, asthma, cough, fibrosis, bronchospasm, etc.

IN VIVO
Airway function (whole body plethysmography) Mouse - Rat - Guinea-pig RES 1
Airway function under hypercapnia (whole body plethysmography) Guinea-pig RES 2
Airway function in large animals Dog - Mini-pig RES 7
Histamine bronchospasm Guinea-pig RES 3
Ovalbumin-induced asthma Guinea-pig RES 5
Citric acid-induced cough Guinea-pig RES 6
Bleomycin-induced pulmonary fibrosis Mouse RES 8
EX VIVO
 Isolated trachea Guinea-pig RES 4

Whole body plethysmography

Respiratory parameters:

- Inspiratory Time (Ti, ms)
- Expiratory Time (Te, ms)
- Peak Inspiratory Flow (PIF, ml/s)
- Peak Expiratory Flow (PEF, ml/s)
- Tidal Volume (TV, ml)
- Respiratory Rate (ResR, breaths/min)
- Relaxation Time (Tr, ms)
- Pause = (Te - Tr)/Tr
- Enhanced Pause (Penh) = Pause x PEF/PIF
- Minute volume (MV, ml/min) = (TV x ResR).

Bleomycin-induced pulmonary fibrosis in mice

• Intra-tracheal administration of bleomycin induces:

– Leukocyte infiltration into the airways

– Fibrosis, multifocal peribronchiolar inflammatory changes (infiltration of neutrophils, macrophages and lymphocytes) and hyperplasia of alveolar and bronchiolar epithelial cells

→ Good correlation between Ashcroft score and inflammatory changes

Ovalbumin-induced asthma in guinea-pigs

• Salbutamol has protective effects against ovalbumin-­‐induced acute bronchoconstriction. In contrast and as expected, it has no protective effects against airway inflammation.

Cough model in the guinea-pig

• Codeine decreased citric acid-­‐induced cough as compared to vehicle control group.