Phosphodiesterase Inhibitors: History of Pharmacology - Phosphodiesterases as Drug Targets - page 26

Table 6 Animal models for studies of airway diseases
Pathophysiology Pretreatment Challenge Read-out PDE involved

Bronchoconstriction,
anaesthetised or conscious

Healthy His, Ach, PAF, LTD 4 Protection vs. bronchoconstriction 3/4

Hyperreactivity PAF,

OVA-sensitisation

Ach, His,
Adenosine

Dose/response curve,
PC20

3/4, 4,
4

Allergic inflammation OVA-sensitisation OVA, Inhalative Protection vs. bronchoconstriction,

BAL, cell influx, eosinophilia

4

Systemic inflammation Healthy LPS iv TNF a release, BAL, cell influx,

neutrophilia

4

Pulmonary inflammation Cigarette smoke, 3-11

days

Chronic neutrophilia 4

Emphysema Cigarette smoke, 6

months

Chronic BAL cell influx, parenchymal

destruction

Pulmonary hypertension MCT, 2-4 weeks;

hypoxia, 2 weeks

Chronic Pulmonary artery pressure,

vascular remodelling

4, 5

Fibrosis Bleomycin, 2 weeks Chronic Pulmonary artery pressure,

vascular remodelling

4

The anaesthetised guinea pig was the mainstay model in 1980 for measuring airway mechanics translating to bronchoconstriction during the asthma attack.
Transition to conscious animals and to quantification of pulmonary inflammation was developed when the mechanistic concept of airway hyper-reactivity and
the underlying inflammation was penetrated in 1989. COPD models were established after 1990