19 Nov

Utility of Animal Models in the Study of Human Airway Disease: Experimental Models (Part 8)

Airway Microcirculation
In patients with severe bronchial asthma, the airway mucosa is morphologically characterized by microvas-cular congestion and edema of the airway wall. These findings suggest that the airway circulation participates in the asthma-associated airway inflammation. Since the airway circulation is difficult to study in humans because of the requirement of invasive techniques, animals have been used to answer questions about the vascular manifestations of asthma. Airway anaphylaxis in animals has been the best studied model in this regard. In allergic sheep, inhalation challenge with specific antigen has been shown to lead to an increase in total bronchial blood flow which corresponded to the immediate increase in airflow resistance; pharmacologic blockade studies showed that the changes in blood flow were not caused by bronchoconstriction. The allergen-induced increase in blood flow may be accompanied by microvascular hyperpermeability as demonstrated by Persson et al who found increased macromolecular transport from the airway vasculature to the airway lumen in allergic guinea pigs as early as five minutes following local antigen challenge. Similarly, intravenously administered ovalbu-mine has been shown to cause Evans blue extravasation in the conducting airways of sensitized guinea pigs.
The histologic demonstration of subepithelial edema and capillary engorgement in sensitized rats and guinea pigs during inhalation challenge with antigen or during systemic anaphylaxis is in keeping with the physiologic findings. Locally released histamine, platelet activating factor, prostacyclin, bradykinin, sulfidopeptide-leukotrienes, tachykinins, and reactive oxygen radicals have all been shown to either increase airway blood flow or increase micro-vascular permeability or both in different animal species.

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